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BSHI

British Society for Histocompatibility and Immunogenetics

NEWSLETTER 85 ISSUE 4 JANUARY 2012

ESOT/BSHI Conference 2011 Andrea Butterfield, NHSBT, Newcastle. BSHI and The European Society for Transplantation (ESOT), joined forces to create what ESOT termed “a meeting with a difference” and it certainly was. This conference was HUGE! With over 3000 delegates compared to the usual BSHI contingency of around 100-150, this conference was a gathering of some of the leading European experts in the field of transplantation. The ‘BSHI conference’, a meeting within a meeting at the ESOT conference, officially began at three PM on Sunday September 4th though other lectures and symposia began before this from 8AM onwards. These included the joint ESOT, European Federation of Immunogenetics (EFI) and BSHI joint symposium entitled, ‘Solid phase assays in kidney transplantation: Too much for far too little?’ The opening address by Paul Sinnott preceded the Terasaki lecture given by Marlene Rose of Harefield Hospital, London, on direct and indirect recognition, accommodation and the Injury hypothesis. This was followed by oral presentations by aspirants for this year’s Young Scientist Award. These included studies by Steven Jervis et al on graft versus host disease severity following a homozygous gene deletion, a Supported by Abbott Diagnostics, Alpha Biotech Ltd, Invitrogen Transplant Diagnostics, Quest Biomedical, Savant Ltd, StemCell Technologies and VH Bio Ltd.

The Clyde, affectionately known locally as ‘The Armadillo’.

study by James Jones et al on MFI thresholds for DSA, comparing Luminex single antigen bead assays with flow and cytotoxic crossmatches, a study by Anna Barker et al on purified lymphocyte use in flow cytometry crossmatches and two studies presented by David Lowe who went on to win this category. He presented some aspects of his research including: sensitisation modes generating different quantities and classes of IgG alloantibodies and how MFI reflects true serum antibody levels but only up to a certain threshold, after which linearity was lost. He reported this to be around 5000 MFI in his laboratory. The first evening concluded with a

theatrical opening ceremony in Glasgow’s iconic auditorium, The Clyde, affectionately known locally as ‘The Armadillo’. This was, for me, the first hint of how large this conference really was. The speakers themselves appeared tiny on the enormous stage. However, each presentation in The Clyde, where all of the plenary sessions were held, was facilitated by two large screens. One screen showed the speaker and the other, their presentation slides. This was not the only technical innovation of this conference. The technological component was to be characteristic of the ‘conference with a difference’ and featured heavily throughout. All plenary

BSHI 1

BSHI Volume 85 – 2012 Issue 4 ©2012 The British Society for Histocompatibility & Immunogenetics

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British Society for Histocompatibility and Immunogenetics

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British Society for Histocompatibility and Immunogenetics

Editorial We begin the 85th edition with a comprehensive article from Newcastle–based Andrea Butterfield on the recent BSHI/ESOT conference held in Glasgow late last year, highlighting both the size and diversity of the meeting. Also within this issue, Professor Phil Dyer introduces us to the “Introductory Programme to Transplantation” qualification and what the program entails. Dr Susan Martin has kindly contributed a piece outlining the amendments to the structure and constitution of the BSHI educational board and outlines the reason for change. We also have our first chairperson’s report from the new BSHI chairperson Dr Susan Fuggle. We have a report on the BSHI 2011 AGM, giving us an update on all things BSHI, whilst David McKenzie and Victoria Robertson report back on the recent CHAIN meeting held in Glasgow. Further to the usual features of the newsletter we have an interesting insight into the latest One Lambda workshop which took place last summer in Dubrovnik, Croatia by Filton-based Jessica Ward. As usual, the newsletter team would like to extend their gratitude to all who have contributed to this edition of the newsletter. Our thanks also go to Arthi Anand who is stepping down as submissions editor of the newsletter to take up the position of meetings secretary. She is replaced by David McKenzie from Glasgow – welcome to the team David.

CONTENTS ESOT/BSHI conference 2011

1,4-5

Editorial

3

The Introductory Programme to 6-7 Transplantation JBL

8-10

Chairperson’s Report

12

BSHI Committee Report

13-15

Amendments to the structure and constitution of the BSHI Education Board

19-20

CHAIN meeting report 12th One Lambda European Clinical Workshop 21st-24 June 2011, Dubrovnik

This is your newsletter and the editorial team are always happy to accept comments, ideas or suggestions you may have for future publications. Enjoy your newsletter, The editorial team.

Deadline for submission of articles in 2012

BSHI CORPORATE MEMBERS

Volume 86, Issue 1 - 6th February 2012. Volume 87, Issue 2 - 7th May 2012. Volume 88, Issue 3 - 6th August 2012. Volume 89, Issue 4 - 5th Nov 2012. Volume 90, Issue 1 - 4th February 2013.

Abbott Diagnostics, Alpha Biotech Ltd, Invitrogen Transplant Diagnostics, Quest Biomedical, Savant Ltd, StemCell Technologies and VH Bio Ltd Charity No. 1123760 British Society For Histocompatibility and Immunogenetics, all rights reserved.

British Society for Histocompatibility and Immunogenetics. A company limited by guarantee. Company No. 6078396. Registered in England and Wales at 12 Coldbath Square, London, EC1R 5HL. Registered Charity Number: 1123760

(No part of this publication may be reproduced or transmitted in any form or by any means, including photocopying and recording, without the written permission of the publishers, or where appropriate, the author of the article. Such written permission must also be obtained before any part of this publication is stored in a retrieval system of any nature, except those directed by BSHI itself.) Opinions expressed by any contributor to this Newsletter are not necessarily those of the Editor, or of the BSHI, and neither the Editor nor BSHI accepts any responsibility or liability for any article or part thereof.

Editorial Board: Faye Mather – Production Editor John Smith – Web Designer Sarah Corbett – Co-Editor Laura Roche – Co-Editor Ruth McCurtin – Co-Editor Louise Onions – Co-Editor Steven Jervis – Co-Editor Arthi Anand – Co-Editor Submissions to: David McKenzie. Histocompatibility & Immunogenetics Service, Gartnavel General Hospital, Level 1, Laboratory Medicine Building, 21 Shelley Road, Glasgow, G12 0XL. Tel: 0141 301 7755 Email: David.McKenzie@ggc.scot.nhs.uk Advertising Enquiries to: Ruth McCurtin Tel: 0113 206 4579 Email: Ruth.McCurtin@Leedsth.nhs.uk

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British Society for Histocompatibility and Immunogenetics

Continued from page 1 the ESOT lectures and oral presentations. Each day diverse parallel symposia were held giving delegates the opportunity to tailor the conference to suit their own needs and gain more relevant knowledge and information. Some of the sessions related to broad categories such as the heart, liver, kidney, lung, pancreas and islet transplantation but others were more peripheral to the mechanics and immunology of transplantation and included symposia on infections, ethics and marginal organ usage as well as current research into all areas of transplantation. Not all of the ESOT lectures were of primary interest to a BSHI audience, being more concerned with the surgical aspects of transplantation, however, there were still ample alternative sessions, presentations and trade stands to visit, it also meant that our BSHI colleagues had opportunities to acquire more understanding of other aspects of transplantation.

An Inflatable networking zone sessions and some of the larger lectures were accompanied by a live web feed for those delegates unable to attend. There was an smartphone app. available for following the conference timetable as well as highlights and additional information and there was an internet hub for delegates to follow conference activities online. Oral presentations of information displayed on posters was performed using electronic displays and

some of the conference material was available for representatives to carry home with them for later reference on a flash drive or CD. The next two days of BSHI conference activities all commenced in the late afternoon. Therefore, throughout the morning and early afternoon BSHI delegates were free to experience the other aspects of transplantation through

Tuesday’s BSHI session began with a touching lecture on Hilliard ‘H’ Festenstein given by Cristina Navarette, reminding us all of the remarkable life this man lead, the rights he defended and the achievements he gained with his team. This was followed by an interesting insight into stem cell research. Paul Sinnott then hosted the AGM as his final duty as chair. Within this session Derek Middleton advised the BSHI delegates of the ongoing and potential new studies whose results are to be announced and discussed at next year’s 16th International Histocompatibility Workshop and invited all centres to participate. The final part of the AGM consisted of the Awards Ceremony where this year’s successful delegates were handed their BSHI Diploma certificates. Paul Sinnott welcomed Sue Fuggle as the new chair of BSHI and retired from his role. Paul’s

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British Society for Histocompatibility and Immunogenetics

ESOT/BSHI Conference 2011.... continued achievements during his tenure were recognised in a short presentation. The critical role of the H&I laboratory featured recurrently at the conference but especially on the final day for the joint ESOT, EFI, BSHI session on Histocompatibility. Several issues presented demonstrated that there is increased attention to, and recognition of the importance of our work in the development of clinical transplantation. Data from a ten year retrospective study was presented questioning whether HLA matching in renal transplantation is still beneficial in light of other improvements in transplantation such as immunosuppressive drugs. The short answer is yes. The study showed that HLA matching is still a significant factor in a successful transplantation. Future developments for H&I testing and support were also discussed at this session, along with the issues raised by recent technological developments. For example, while over 4000 class I alleles have been detected, making matching more difficult, there are just 146 class I epitopes. This may provide a future matching strategy or at least a means of viewing mismatched epitopes rather than antigens for their potential immunogenicity. Further to this, the balance of utility versus equity for organ transplantation was debated, i.e. the balance of performing safe transplants versus preventing possible transplants by listing certain antibodies as unacceptable antigens for transplant. In particular, should a transplant be denied when ‘Luminex only’ donor specific antibodies (DSA) are detected? Also when some but not all broad antigen specific Luminex beads are positive (e.g. possible ‘allelespecific’ antibodies), do we assign these as broad antigen specific DSA and potentially, unnecessarily restrict donor choice or do we then begin high resolution typing solid organ patients and donors?

Until such a time that we can answer these questions confidently, policies on when to transplant may be based on risk assessment and possible outcomes of transplanting and also which of these risks are reversible and treatable. A show of hands allowed the laboratories concerned to show how many of us perform virtual crossmatches, transplant across B cell positive flow crossmatches and/or HLA match for any organs other than kidneys. The discussions focussing on H&I over the three days demonstrated that great changes are occurring and with them, new areas of interest and research. Currently there are more ABO and HLA incompatible transplants being performed, while new interim support such as extracorporeal membrane oxygenation (ECMO) and ventricular assist devices (VAD) in cardiac transplantation have brought new challenges in cardiac transplant strategies.

accustomed to using the Luminex platform for measuring antibodies, different centres are questioning the relevance of MFI values when comparing results with other laboratories. We are examining and comparing the abilities and shortcomings of the different kits available including the newer complement activating antibody detecting kits and questioning the relevance of ‘Luminex only antibodies’. As one speaker put it in this session, ‘we are not at the cutting edge of technology; we are at the ‘bleeding edge’. Next year the BSHI conference joins with EFI in Liverpool and the 16th International Histocompatibility Workshop. I am sure that the 2011 delegates will be have been inspired at this conference to return with many research ideas to their centres for presentation in 2012. BSHI would like to thank Quest Biomedical and VH Bio for their generosity in sponsoring travel bursaries for ESOT 2011.

Additionally, we have increasing long term data from routine Luminex usage at many centres. As we become more

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British Society for Histocompatibility and Immunogenetics

The Introductory Programme to Transplantation – a pan-European qualification The ESOT sponsored course “Introductory Programme to Transplantation” (iPT) is open to registration (www.esot.org). As Chair of the ESOT Education Committee I am eager to promote this course within the H&I community.

The final assessment will be in June when a final set of MCQs must be answered (50% for a pass) on a specified day. iPT will work to ensure that MCQs relevant to the students discipline, such as H&I, are available.

The aim of iPT is to provide an entry level, widely based qualification across the whole of transplantation which can be achieved by medics, nurses, coordinators and scientists. The iPT / ESOT certificate will be evidence that an individual has achieved the necessary knowledge to proceed to the next level of training. Possession of the iPT certificate will be useful to those who plan to move their place of work elsewhere in Europe and to those who wish to undertake other ESOT sponsored training and education. It will be recognition of the intent of an H&I trainee to pursue an active career in H&I.

I hope that H&I staff in the UK will value iPT as a qualification. I will be pleased to answer any questions on the iPT course. phil.dyer@nhs.net

The first iPT module on “Immunobiology” (A Warrens) and the second on “H&I” (F Claas) are followed by MCQs after which there are a further 12 modules covering transplant surgery (most organs), posttransplant care and finally ethical issues in transplantation. The modules contain a wealth of background information compiled by recognised international experts. I would expect a commitment of a day each month to be required for each module. All modules are released online and all assessments are online. The registration fee for non-medics is 300Euros.

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Journal Based Learning Cycle 39 Answers Blood Transfusions in Organ Transplant Patients: Mechanisms of Sensitization and Implications for Prevention. J. C. Scornik1,*, H.-U. Meier-Kriesche2 American Journal of Transplantation. Volume 11, Issue 9, pages 1785–1791, September 2011 1.

Erythrocytes express between 100 and 2000 HLA class I molecules per cell.

True

2.

HLA-A2 is responsible for the blood group antigen Bg .

False

a

3.

Blood transfusion is not noted to have an immune modulating effect.

False

4.

Immune reactivity to blood transfusion increases with age.

False

5.

The immunogenicity of blood transfusions is related to the number of units transfused.

True

6.

The titre of HLA antibodies present in the blood of patients having previous pregnancies is of a higher titre True following blood transfusion than patients with no pregnancies.

7.

Matching for HLA-A and –B antigens contributes to reduced sensitisation following graft loss.

True

8.

Patients transfused with leukocyte depleted blood do not produce HLA antibodies.

False

9.

Leucocyte depletion confers protection against allosensitisation.

False

10.

A decrease in blood transfusion in renal disease patients is associated with the use of erythropoietin stimulating True agents rather than trying to avoid sensitisation.

11.

Where blood for transfusion is HLA matched with the patient, there is an increased risk of sensitisation.

12.

Multiparous retransplant patients and paediatric patients would benefit the least from HLA matched blood False transfusions.

13.

HLA matched blood transfusions carry a decreased risk of developing graft versus host disease.

True

14.

HLA matched blood should never be irradiated prior to transfusion.

False

15.

The use of immunosuppressants has been shown to decrease the risk of HLA sensitisation due to blood True transfusion.

16.

The administration of blood transfusion to patients with functioning grafts was not associated with HLA True sensitisation.

17.

Blood can be given with no added sensitisation risk to transplant waiting list patients and therefore no need to False assess possible consequences.

18.

Education by professional bodies should emphasise prevention rather than treatment for sensitisation in True transplant patients.

19.

Patients with a failed graft but not needing a nephrectomy do not benefit from continuing immunosuppression. False

20.

Sensitisation by blood transfusion is unavoidable in transplant patients due to the presence of HLA molecules False on the surface of red cells.

Scoring CPD points will be awarded as follows: 0-10 correct 0 points 11 – 14 correct 1 point

Score:

15 – 19 correct 2 points

CPD Points:

20 correct 3 points

Signed:

(on behalf of the BSHI PDE)

BSHI 8 BSHI Volume 85 – 2012 Issue 4 ©2012 The British Society for Histocompatibility & Immunogenetics

False


British Society for Histocompatibility and Immunogenetics

BSHI Continuing Professional Development

Journal Based Learning The CPD JBL questions can be found on the BSHI website, and you must now submit your answers electronically via the website. CPD Points

The question/answer cards will be marked and scored by an assessor appointed by the PDE. Points will be awarded on the basis of: 0-10 answers correct – 0 points, 11-14 correct – 1 point, 15 – 19 correct – 2 points, all 20 correct – 3 points.

How to participate

If you are registered on the BSHI CPD scheme, then you are eligible to participate in the Journal Based Learning scheme. All you need to do is read the reference article given at the top of the answer card, and then answer the question statements by choosing true or false for each of the 20 statements relating to the article. Go to http://www.bshi.org.uk/members/cpd_questions.html Then fill in your name, contact address, e-mail address and BSHI membership number. Simply click on your choice. Any answers that are not clear, or are ambiguous, will not score.

John Harvey NHS Blood and Transplant - Filton 500 North Bristol Park, Northway, Filton, Bristol, BS34 7QH The deadline for submission of completed cards for this cycle is: 29th February 2012. Your answers will be assessed and returned to you with the number of CPD points earned, for inclusion in your BSHI CPD folder. Any members not currently registered on the CPD scheme, but interested in joining should contact the BSHI PDE; details in the Newsletter

If you have any comments or suggestions about the journal based learning series and the topics/articles chosen, we would like to hear from you. Please contact the PDE (details in Newsletter) or e-mail j.harvey@nhsbt.nhs.uk

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British Society for Histocompatibility and Immunogenetics

Journal Based Learning Cycle 40 Donor –specific anti-HLA Abs and graft failure in matched unrelated donor hematopoietic stem cell transplantation. Stefan O. Ciurea, Peter F.Thall, Xeumie Wang et al., Blood, 2011, 118, 22, 5957-5964 All CPD returns to be made by the BSHI internet link. Deadline for submission of completed answer cards: 29th February 2012. 1.

26% of MUD transplants are mismatched for DP.

True

False

2.

Treatment related mortality is no longer due to graft failure because of improved patient care and True HLA matching.

False

3.

In this study, there were 32 observed mismatches in the HLA-DRB3 locus.

True

False

4.

In this study there were 10 observed mismatches in the HLA-DRB4 locus nine of which involved True null alleles.

False

5.

Donor specific antibodies (DSA) were found against HLA-B locus antigens.

True

False

6.

116 transplants were performed with recipient HLA antibodies reactive to donor antigens.

True

False

7.

1.4% of recipients had donor specific antibodies reactive against HLA-DPB1.

True

False

8.

All anti-DP antibodies detected were donor reactive.

True

False

9.

The highest percentage of graft failures was accounted for by the presence of anti HLA antibodies. True

False

10.

No association was identified between graft failure and type of conditioning therapy.

True

False

11.

All patients with DSA’s were female.

True

False

12.

30.8% of women and 12.1% of men had anti HLA antibodies in this study.

True

False

13.

Where women had no previous pregnancies their sensitisation level was the same as for men.

True

False

14.

Of the patients with anti-DP antibodies, only four of them were matched at DP for their donor.

True

False

15.

8 patients with DSA’s against HLA-DP were transplanted, of which 3 failed to engraft.

True

False

16.

Anti-DP DSA’s are not associated with increased risk of graft failure as only 3 of the 592 transplants True failed where they were present.

False

17.

The DSA antibodies detected were IgG in subclass; this would suggest possible T-cell involvement True in the recognition process of mismatched antigens.

False

18.

The antibody MFI’s differentiated engrafted and non engrafted patients with DSA antibodies True present.

False

19.

Animal models indicate that passive transfer of anti HLA antibodies can reject donor haematopoietic True stem cells.

False

20.

In this study 2 patients were treated prospectively to reduce DSA’s.

True

False

Scoring CPD points will be awarded as follows: 0-10 correct 0 points 11 – 14 correct 1 point

Score:

15 – 19 correct 2 points

CPD Points:

20 correct 3 points

Signed:

(on behalf of the BSHI PDE)

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British Society for Histocompatibility and Immunogenetics

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BSHI Committee Members British Society for Histocompatibility and Immunogenetics (from 2011 AGM)

President: Dr Jackie Cornish Start: AGM 2008 Finish: AGM 2012 Chairperson: Sue Fuggle Start: AGM 2011 Finish: AGM 2014 Tel: 01865 226162 Email: susan.fuggle@nds.ox.ac.uk

Chairperson’s Report This is my first report since becoming Chair of our society and I would like to take the opportunity to thank Paul Sinnott for all his hard work in so ably chairing the society and ensuring that the profile of H&I remains high in all of the current discussions impacting on our discipline. I would also like to welcome new Committee members; Deb Singleton (WTAIL) and Aliyye Karasu (Anthony Nolan), Kay Poulton (Manchester) as Chair of the Professional Advisory Group (BPAG) and David Turner (Edinburgh) as Secretary Elect. Arthi Anand finished her term as an Ordinary Member, but we are delighted that she will remain on the Committee as Meetings secretary. Thanks, too, to Arthi for all the work she did as Submissions Editor for the newsletter team and to David McKenzie who has taken on this role. The Committee met on 9th November and a report of that meeting will be included in the next newsletter, but there are a few items to highlight now. There is currently a vacancy for an Ordinary Member on the main committee and vacancies on other committees. I would like to encourage members to consider becoming actively involved in the work of the society. Many members will be able to testify to the rewards from involvement. It has been a busy time for the Education Board and the Professional Advisory Group. One particularly important matter is the consultation by the Department of Health on the transposition of the EU Directive on standards of quality and safety of human organs intended for transplantation (EUODD) and the Human Tissue Authority’s consultation on the Framework document which describes the proposed implementation of the directive. This is ongoing at the time of writing and we will await the responses from the DoH and HTA. Plans for the BSHI conference 2012 in Liverpool are well advanced. This joint meeting with EFI and the International Histocompatibility Workshop will be a stimulating event. Dr Jackie Cornish, our Honorary President will finish her term of office at that meeting and we look forward to the presidential address on ‘Paediatric Stem Cell Transplant’ on Sunday 3rd June. Dr Cornish is the most recent in a long line of distinguished scientists and clinicians who have been honorary president. As I

mentioned in my email, the Committee is seeking nominations for the next Honorary President. A description of the role is in the constitution on the website and the committee would be grateful for nominations by February 3rd, 2012. The BSHI has traditionally been represented on the NHSBT Kidney and Pancreas Advisory Groups. The society was approached to provide representatives for the Bowel and the Cardiothoracic Advisory Groups (BAG and CTAG). Expressions of interest were sought from Consultant Scientists in laboratories providing services for those organ transplants and David Briggs now represents BSHI on BAG and John Smith on CTAG. At the recent Committee meeting I asked the members to consider how BSHI should be represented on occasions where there may be a conflict of interest for me as BSHI Chair and as Scientific Advisor to ODT. For example, the BSHI chair is invited to attend meetings of the Chairs of the Advisory Groups and I am also invited as Scientific Advisor. After discussion, the committee decided that a committee member should be nominated to represent BSHI on such occasions. It was agreed that Sue Martin would take on the role as she has experience on the NHSBT Advisory Groups. Currently she is the BSHI representative to PAG and in the past has been the representative to KAG. She will be on the BSHI Committee for 2 years of my 3 year term of office and for the 3rd year, the Chair elect will fulfil the role. Finally, I think it is an important time for the discipline, with many challenges for BSHI members working in research and in the NHS environment alike. There are increasing cost pressures for laboratories, discussions regarding training and the career pathway and development of a national tariff for renal transplantation to name but a few. There is a great network within BSHI and if there are areas where you feel that the Society could be more effective in supporting the membership, please do get in touch. By the time the newsletter is published it will be the New Year, so best wishes to all for 2012.

Secretary: Anthony Poles Start: AGM 2009 Finish: AGM 2012 Tel: 01179 217 533 Email: anthony.poles@nhsbt.nhs.uk Secretary Elect: David Turner Start: TBC Finish: TBC Tel: 0131 2427534 Email: david.turner2@nhs.net Treasurer: Vaughan Carter Start: AGM 2010 Finish: AGM 2013 Tel: 0191 202 4411 Email: vaughan.carter@nhsbt.nhs.uk Meetings Secretary: Arthi Anand Start: AGM 2011 Finish: AGM 2014 Tel: 020 8258 2820 Email: arthi.anand@nhsbt.nhs.uk Membership Secretary: Natalia Diaz Burlinson Start: AGM 2009 Finish: AGM 2012 Tel: 020 3246 0240 Fax: 020 3246 0236 Email: Natalia. DiazBurlinson@bartsandthelondon.nhs.uk Ordinary Members: Deborah Singleton Start: AGM 2011 Finish: AGM 2014 Tel: 01443 622179 deborah.singleton@wbs.wales.nhs.uk Aliyye Karasu Start: AGM 2011 Finish: AGM 2014 Tel: 02072848341 Email: Aliyye.Karasu@anthonynolan.org.uk

David McKenzie Start: AGM 2010 Finish: AGM 2013 Tel: 0141 301 7755 Email: David.McKenzie@ggc.scot.nhs.uk.

Chair BPAG: Kay Poulton Start: AGM 2011 Finish: AGM 2014 Tel: 0161 276 6667 Email: kay.poulton@cmft.nhs.uk Chair BEB: Sue Martin Start: AGM 2010 Finish: AGM 2013 Tel: 0161 276 6215 Email: susan.martin@cmft.nhs.uk

Our thanks also go to all the outgoing BSHI committee members for their valuable contribution.

Sue Fuggle

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British Society for Histocompatibility and Immunogenetics

Report on the BSHI 2011 AGM The AGM took place on 6th September 2011 during the 22nd Annual BSHI Conference, held jointly with ESOT in Glasgow. 72 members were in attendance.

Secretary’s Report - Anthony Poles (presented by Paul Sinnott). Nominations were sought earlier in the year for vacancies on the BSHI Main Committee and the following members were accepted, unopposed: Secretary Elect – Dave Turner (Edinburgh), Ordinary Members – Aliyye Karasu (Anthony Nolan) and Deborah Singleton (Cardiff). One ordinary member vacancy remains. Arthi Anand (Colindale) is the new Meetings Secretary. The role of BSHI representative to the UK NQAAP for Immunology has been advertised with no response to date. 25 bursaries were allocated in 2011: 18 for BSHI, five for EFI, and one each for BBTS and the International Society for Heart and Lung Transplantation meeting. The total sum disbursed was £4425. The online access to journals provided to members by BSHI was renewed with the same journals as before. Increased access was considered, but was not possible due to cost. The journals available and number of full text requests made by BSHI members are published in the Newsletter. The re-designed BSHI website was launched in October 2009. CPD Journal Based Learning is now submitted via the website. BSHI documents are also available on the website. In 2009-10 there were 15,414 visits to the website from 7433 different visitors.

Chairperson’s Report - Paul Sinnott Public Consultation on In vitro Diagnostics Directive: The BSHI response was focussed upon whether the existing exemption from CE marking for ‘in house’ testing should be continued. Arguments in favour of continuing this exemption (flexibility, rapid updating and cost) were made in the BSHI response. The UK response was formulated by the MHRA and this includes advocating retention of the existing exemption for in-house genetic testing. Revision of the IVD Directive into which these consultations will feed will not begin until early 2012. NICE Guidelines on Organ Donation: improving donor identification and consent rates for cadaveric organ donation: Although largely outside the scope of these Guidelines, issues relating to H&I staff training and adequate laboratory resources to match increased availability of potential organ donors were underlined. BSHI is now a recognised stakeholder in the development of these Guidelines. DH Policy Proposal for engagement on ‘Expanding the List of ‘Never Events’: A clause relating to death or injury arising from the inadvertent administration of ABO/HLA incompatible blood/blood products or transplantation of ABO/HLA incompatible organs was included. BSHI responded that solid organ transplant and transfusion issues should be dealt with separately. ABO and HLA incompatible transplants may (and indeed should) be performed when part of agreed and well-supported transplant programmes. Close liaison with the H&I laboratory is essential before HLA incompatible transplant programmes are established. The resulting Policy Framework has now been published.

The White Paper – ‘Equality and Excellence: Liberating the NHS’: BSHI submitted a comment relating to the development of a managed network of H&I laboratories. HLA Matching Guidelines: Draft Guidelines for Selection and HLA matching of related donors, adult unrelated donors and umbilical cord units for haematopoietic stem cell transplantation have been available via the BSHI website for a period of general comment. A revised final draft has been posted for final consultation. EU Directive on Standards of Quality and Safety of human organs intended for transplantation: Powers governing the Articles of this Directive are delegated to member states, who designate one or more competent authorities to enforce its requirements. In the UK the competent authority will be the HTA. Article 7.4 states that ‘the tests required for organ and donor characterisation shall be carried out by laboratories with suitably qualified or trained and competent personnel and adequate facilities and equipment’. Meeting of H&I Lab Directors supporting cardiothoracic transplant programmes: Two meetings of this group were held in order to produce an agreed paper on criteria for listing unacceptable antigens for transplant, based on current antibody screening techniques. As part of this exercise, NEQAS antibody identification data from the labs concerned has been analysed to inform process. The resultant paper was presented and discussed at a meeting with ODT on June 22nd, attended by the Lab Directors (or representatives) and representatives of the Cardiothoracic Transplant units. The aim is to produce an agreed strategy for listing unacceptable antibodies and risk stratification based on Luminex single antigen bead testing.

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British Society for Histocompatibility and Immunogenetics

Report on the BSHI 2011 AGM continued Establishment of RCPath external assessor panel for Consultant Clinical Scientist appointments: BSHI has liaised with the RCPath in establishing an assessor panel for Consultant Clinical Scientist appointments in H&I. This panel has taken over from the current BSHI (formerly DH) panel for Consultant CS appointments, although BSHI will continue to maintain an external assessor panel for non-Consultant appointments at Band 8c and below (it is likely to be the same individuals involved in both panels, at least at present). Renal Association Clinical Practice Guidelines on the ‘Post-operative care of the Kidney Transplant Recipient’: BSHI commented that these Guidelines contained insufficient mention of HLA antibody monitoring. Reference should also be made to the BSHI/BTS Antibody Characterisation Guidelines. ACB; Liaison with other Professional bodies: Issues believed to be of importance by the ACB include financial difficulties facing laboratories such as difficulties replacing staff and reduced training and travel budgets, making it ever more difficult for clinical scientists to attend meetings of, or take up office within, their scientific and professional societies. There may be possibilities for joint action to address common issues. ACS; Academy of Science: The Association of Clinical Scientists agreed to work with the Department of Health in December 2010. The Academy began in earnest at the beginning of this year with the interim appointments of Iain Chambers as Chair and Steve Barnett as CEO. The first Shadow Board meeting in March brought together many of the healthcare science professional bodies (inc BSHI) and saw the initial drafts of the terms of reference and the overarching aims of the organisation.

The next Annual BSHI Conference will be held jointly with the International HLA and Immunogenetics Workshop and EFI in Liverpool on June 1st-3rd 2012.

Membership Secretary’s Report – Natalia Diaz Burlinson There were 404 members at the time of the meeting. 16 new members have joined since the 2010 AGM, 353 members are active and 51 members have not yet renewed their membership. Membership has fallen by 21 since 2010. BSHI documentation is being reviewed and updated to include the new logo. There have been some technical problems with the Membership Database that have affected the sending of group emails with attachments. The issue is being addressed with the database managers.

Treasurer’s Report - Vaughan Carter Accounts for the year ending December 2010 have been audited and will be submitted to Companies House. The income and expenditure account and balance sheet were presented to the AGM. The full accounts are available from the Charities Commission and Companies House, or by request from the BSHI Treasurer. During 2010 BSHI made a profit of £15,007. This compares to a profit of £9583 in 2009, despite the 2010 conference not being as financially successful as 2009. Specific comments relating to the 2010 accounts were: • Subscriptions were received from 399 active members. All seven corporate members have renewed. • Conferences. An additional £3887.80 was received from Sheffield Hallam for the 2009 Conference (final 2009 surplus), as well as £5000 from the

2010 Conference. £1623 was paid in various costs. • Diploma fees were increased from £346.50 to £650 in 2010. All invoices from the BSHI Diploma due in 2010 have been paid. Diploma events show a profit of £1563. • Other training covers national Higher Training activities. These activities made a loss of £1117. • Bursary payments were £4875 in 2010, considerably lower than the £7350 paid in 2009. Bursary awards will be discussed by the Committee. • Governance costs. Regular meeting costs for the Executive Committee were £3759 in 2010, compared to £7676 in 2009. The coding used for the Travel Bureau makes it difficult to assign costs against committees.

Matters arising in 2011: • Subscriptions for online journal access via OVID have been renewed for 2011 and members are encouraged to make use of this facility. In 2010 the cost of each article downloaded was £3.50. • The management of the BSHI Diploma has been put to tender in 2011. • The finances for the 2011 ESOT/BSHI Conference are being run by ESOT, with no profit to BSHI. • An agreement is in place between BSHI, EFI and the IHIW over costs and profit-sharing for the 2012 joint BSHI/ EFI/Workshop meeting. • No increase in membership fees is planned for 2012. The annual charge for the CPD scheme is to be incorporated into the annual membership fee as a benefit to members. One member enquired about the BSHI bank balance, which at the time of the meeting was £86,000.

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British Society for Histocompatibility and Immunogenetics

Report on the BSHI 2011 AGM continued

Education Board Report – Sue Martin Training Executive: Bridget Montague is retiring and was thanked for her contribution to the TE. Karen Stewart has taken on the role of Training Co-ordinator. Modernising Scientific Careers (MSC) Scientist Training Programme (STP): Two H & I trainees, based in Hammersmith and Manchester, are due to start the STP in September 2011. They are undertaking an MSc in Blood Sciences provided by Manchester University. H & I is included as a distinct specialism, Clinical Immunology with H & I. BSHI members commented that MSC has not yet been implemented in the devolved countries. There is one trainee in Wales and four in Scotland following the BSH Diploma. It is the responsibility of heads of labs to insist on funding for trainee posts from their Health Authorities. CPD: A sample H & I portfolio successfully submitted to HPC for an audit of CPD has been placed on the BSHI website. Case studies are invited from members for publication in the BSHI Newsletter. Submission details are in the Newsletter. Changes to the BEB: The Training Executive and Professional Development Executive are being combined to form the Training and Development Executive (TDE). The reasons for the change and the new committee structures are described in an article elsewhere in this Newsletter. One BSHI member asked if it was appropriate that the new TDE constitution was ratified by the main committee and not by the membership. The process followed for ratification of the new TDE constitution and the revised Education Board constitution was as specified in the constitutions of the TE, PDE and BEB.

NHSBT/Anthony Nolan Report – John Harvey As an addendum to the AGM, John Harvey reported on changes to unrelated bone marrow donor searches in the UK. There is to be a single UK-wide VUD registry to be managed by the Anthony Nolan Trust. 20,000 donors will be HLA typed at high resolution. New search instructions will be issued to transplant units from October 2011. WBMDR searches will be integrated soon. Searches for all UK patients will be co-ordinated via ANT. BBMR will co-ordinate international searches for UK donors for all three registries.

Award presentations The following members completed the BSHI Diploma in 2011 and were presented with their Diplomas at the AGM: Zdenka Bacovska

The Life Technologies Young Investigator Award was presented to David Lowe from Birmingham for his presentation, “Class I HLA-Specific antibody quantification”. Best Abstract was won by Martin Stern from Basel for his presentation, “The position of the natural killer cells activating KIR genes protect from reactivation of cytomegalovirus infection after kidney transplantation”. Best Poster was won by David Keegan from Dublin for his poster, “Flow crossmatch results in combination with 2 different single antigen assays provide greater resolution in predicting renal graft survival”. Finally, Sue Fuggle, the incoming Chairperson, made a presentation to Paul Sinnott in recognition of his contribution to the Society over the last three years as Chairperson.

Hammersmith/ Anthony Nolan

Andrea Butterfield Newcastle Sarah Edwards

Barts and the London

Maissa El-Khatib

Hammersmith

Nicola Gunby

Hammersmith

Gemma Hopkins

Cambridge

Steven Jervis

Manchester

Flavia Namaganda Guys Agnieszka Ojrzynska NHSBT, Colindale Helen Wicks

Cardiff

Zoe Williams

Manchester

Well done to all on their success!

BSHI 15 BSHI Volume 85 – 2012 Issue 4 ©2012 The British Society for Histocompatibility & Immunogenetics

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British Society for Histocompatibility and Immunogenetics

THE BRITISH SOCIETY FOR THE BRITISH SOCIETY FOR HISTOCOMPATIBILITY IMMUNOGENETICS HISTOCOMPATIBILITYAND AND IMMUNOGENETICS Committees, Subcommittees and Committees, Subcommittees andWorking WorkingGroups Groups Main BSHICommittee Committee Main BSHI

Chairperson, Secretary, Treasurer, Meetings Secretary, Chairperson, Secretary, Treasurer, Meetings Secretary, BEB Chairperson, Chairperson, 66 ordinary committee members BEB Chairperson, BPAGBPAG Chairperson, ordinary committee members

BSHIProfessional ProfessionalAdvisory Advisory BSHI Group (BPAG) Group (BPAG)

BSHIEducation Education Board BSHI Board(BEB) (BEB)

Special SpecialInterest Interest Groups Groups (SIG) (SIG) Haemopoietic Stem Cell Haemopoietic Stem (HSC ) ) Cell(HSC Antibody Antibody

TrainingExecutive Executive (TE) Training (TE)

BSHI Honorary BSHI HonoraryPresident President

Professional ProfessionalDevelopment Development Executive (PDE)

Executive (PDE)

ResearchExecutive Executive (RE) Research (RE)

Standards Standards Working Working Group Group BSHI Chairperson BSHIrepresentatives ChairpersonSIG SIG representatives UK members of EFI Standards Committee UK members of EFI

Professional Representatives/ Professional Representatives/ Contacts Group Contacts Group

Standards Committee

BSHI representatives to other professional societies/organisations Organisation

Member’s Name

Term of office

Ends

Tel No./Email

Association of Clinical Scientists (ACS)

David Turner

As required

N/A

david.turner2@nhs.net 0131 2427534

British Society for Immunology (BSI) Committee

Noel Collins

3 years

2013

noel.collins@nhsbt.nhs.uk 0114 358 4849

Clinical Pathology Accreditation (UK) Ltd (CPA)

Craig Taylor (Specialist advisor in H&I)

3 years

2013

craig.taylor@addenbrookes.nhs.uk 01223 217741

International Journal of Immunogenetics (IJI)

Noel Collins

3 years

2013

noel.collins@nhsbt.nhs.uk 0114 358 4849

NHSBT Bowel Advisory Group

David Briggs

3 years

2014

David.Briggs@nhsbt.nhs.uk 0121 253 4099

NHSBT Cardiothoracic Advisory Group

John Smith

3 years

2014

j.smith@rbht.nhs.uk 01895 828774

NHSBT Kidney Advisory Group

Andrea Harmer

3 years, extended by one year

2012

andrea.harmer@nhsbt.nhs.uk 0114 358 4800

NHSBT Pancreas Advisory Group

Sue Martin

3 years, extended by one year

2012

susan.martin@cmft.nhs.uk 0161 276 6215

Royal College of Pathologists H&I Sub-committee

Terry Horsburgh Andrea Harmer (chair)

3 years

2014 2013

terry.horsburgh@uhl-tr.nhs.uk 0116 258 4606 andrea.harmer@nhsbt.nhs.uk 0114 358 4800

UK NEQAS Quality Assurance Advisory Panel in Immunology

Vacant

British Transplantation Society

Craig Taylor (Councillor for Histocompatibility)

2 years

2012

craig.taylor@addenbrookes.nhs.uk 01223 217741

European Federation for Immunogenetics Standards Committee

Sue Fuggle Kay Poulton (chair)

As required

N/A

susan.fuggle@nds.ox.ac.uk 01865 226162 kay.poulton@cmft.nhs.uk 0161 276 6667

Institute of Biomedical Sciences

David Wilson

As required

N/A

david.wilson3@nhs.net 01224 6552858

Royal College of Pathologists Standing Committee for Clinical Science

Paul Sinnott

3 years

2014

paul.sinnott@bartsandthelondon. nhs.uk 020 7377 7699

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British Society for Histocompatibility and Immunogenetics

Members of the Training and Development Executive Chair

Amanda Robson

Amanda.Robson@cmft.nhs.uk

TBC

Secretary

Rob Whittle

Robert.Whittle@rothgen.nhs.uk

TBC

BSHI Diploma Co-ordinator

Karen Stewart

karenm.stewart@nhs.net

TBC

Higher Specialist Scientific Training Lead

Tracey Rees

tracey.rees@wbs.wales.nhs.uk

TBC

Higher Training Co-ordinator

Alison Logan

alison.logan@cmft.nhs.uk

TBC

CPD Co-ordinator

Jane Matthews

jane.matthews@nhsbt.nhs.uk

TBC

Journal Based Learning Co-ordinator

John Harvey

john.harvey@nhsbt.nhs.uk

TBC

MSC Link

Sue Davey

sue.davey@nhsbt.nhs.uk

TBC

Meetings Secretary

Shahram Hemmatour

Shahram.Hemmatpour@nhsbt.nhs.uk

TBC

BSHI Diploma Representative

TBC

Higher Specialist Trainee Representative

Katherine Poole

katherine.poole@leedsth.nhs.uk

TBC

Ordinary Member

Jeanette Ayers

Jeanette.Ayers@orh.nhs.uk

TBC

Ordinary Member

Vaughan Carter

vaughan.carter@nhsbt.nhs.uk

TBC

Ordinary Member

Stephen Sheldon

stephen.sheldon@cmft.nhs.uk

TBC

Ordinary Member

David Smillie

david.smillie@nhsbt.nhs.uk

TBC

Ordinary Member

John Smith

j.smith@rbht.nhs.uk

TBC

Ordinary Member

Stephen Weston

stephen.weston@uhl-tr.nhs.uk

TBC

TBC

BSHI Diploma viva dates and deadlines 2011 Work Submission Deadline

Application for viva deadline

Viva week

20th February 2012

19th March 2012

16th-20th April 2012

18th June 2012

16th July 2012

13th-17th August 2012

15th October 2012

12th November 2012

10th-14th December 2012

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British Society for Histocompatibility and Immunogenetics

RE Membership Term

To

Term

To

Term

Chairperson Robert Vaughan robert.vaughan@kcl.ac.uk

AGM TBA

Ordinary Member John Girdlestone John.Girdlestone@nhsbt.nhs.uk

AGM 2014

Ordinary Member Vacancy

Secretary Noel Collins Noel.Collins@nhsbt.nhs.uk

AGM 2013

AGM Ordinary Member Katy Latham 2012 Katy.Latham@anthonynolan.org

AGM Ordinary Member David Briggs 2012 David.Briggs@nhsbt.nhs.uk

AGM Ordinary Member Susan Tonks 2013 susan.tonks@admin.ox.ac.uk

To

Ordinary Member Vacancy

BSHI On-line Journal Access

The table below shows the number of full text requests that have been made by BSHI members from the BSHI on-line journal facility during 2011.

Journal

Jan

Feb

Mar Apr

May Jun

Jul

Aug

Sep

Oct

Total

HTML

PDF

American Journal of Transplantation

58

47

78

22

174

52

51

90

71

42

685

144

541

American Journal of Transplantation Supplement

0

1

8

0

5

2

0

1

0

0

17

10

7

Bone Marrow Transplantation

74

63

37

45

81

13

33

36

53

11

446

67

379

Current Opinion in Hematology

9

15

17

5

18

2

6

5

16

14

107

34

73

Current Opinion in Organ Transplantation

73

75

39

37

66

28

22

99

39

44

522

104

418

Immunological Reviews

20

51

15

24

34

13

6

30

36

13

242

87

155

Transplantation

175

157

131

118

225

136

70

229

198

82

1521

435

1086

All Journals

409 409 325 251

603 246 188 490 413 206

3540

881

2659

Any BSHI member interested in joining the Research Executive should contact the Chairperson or Secretary.

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British Society for Histocompatibility and Immunogenetics

Amendments to the structure and constitution of the BSHI Education Board Background The Education Board (BEB) was formed in the late 1990s in order to bring together all the education, training and research functions of BSHI so that they could support one another. The erstwhile Training Board was already established and was responsible for managing the training scheme. This became the Training Executive and the exit qualification from the training scheme was re-named the BSHI Diploma. At that time BSHI had an official link to the British Society for Immunology through the H&I affinity group (HIG) which became the Research Executive within the BEB. In addition, the requirement for a CPD scheme relevant to H&I was acknowledged and the Professional Development Executive (PDE) was established to set up and run such a scheme for BSHI members. Around the same time, H&I became recognised as a specialism within the Royal College of Pathologists and a curriculum and examinations were being developed and so the BSHI representative to the College became a member of the BEB. Subsequently, to support work on an IBMS specialist diploma in H&I and higher specialist examinations, an IBMS member was co-opted.

Functions of the TE Management of the BSHI Diploma • • • • • • •

Administrative functions are now managed externally by Kingston Smith Review and updating of log books, essay titles and essay plans Log book assessments Marking of essays and case studies Mid-term assessments Oral examinations Organisation of training meetings (single day and 2-day p.a.)

With the implementation of MSC it is envisaged that the number of Diploma registrants will decline.

Current membership • • • • •

Chair Co-ordinator Secretary Meetings organiser 8 ordinary members

Functions of the PDE

Drivers for change • Numbers of registrants to the current BSHI Diploma training scheme will decline • Despite the above, it is increasingly difficult to attract new TE members who are essential for assessing the work

Taking time out of the workplace is becoming increasingly difficult

• Involvement of BSHI in delivering HSST will increase and interaction with the RCPath will have to be strengthened • Graduates from the MSC STP route will require educational support as they move into the HSST programme • It is now envisaged that the ACS will It is envisaged this commitment develop into the Academy of will increase with the introduction Healthcare Science. It is crucial that the BEB is kept up to date with both of a MSC HSST route the competencies required to achieve Functions of the RE the ACS certificate of attainment and Historic links with the BSI are now limited. also future requirements There may be future opportunities to • Future training at both the STP and organise an H&I session at a BSI congress HSST levels will encompass elements but these will not be frequent. Activities of current BMS and CS training and so it is crucial that links with the IBMS currently involve: are strengthened • Organisation of RE session at annual • It is important for BSHI to have an BSHI conference (not required for awareness of an involvement with the 2011 and 2012) • Inviting speakers for Festenstein and development of H&I training in Europe Terasaki lectures at annual • There is a willingness from the RE to conference become involved in the identification • Receiving and marking abstracts submitted for BSHI annual conference of speakers for higher training meetings and to have a greater • Liaising with the BTS for the organisation of the H&I session at the involvement in the overall planning of the programme for the BSHI annual annual BTS congress conference • Providing the Science Watch article Continued on next page for the BSHI newsletter • Management of CPD scheme • Management of journal based learning • Organisation of higher training meetings • Contribution to higher specialist training group

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Amendments to the structure.... continued

Agreed changes

1.

In the context of MSC BSHI’s commitment to supporting the future training and development needs of its members will be strengthened by combining the TE and PDE in to a Training and Development Executive. This will facilitate the sharing of some functions while widening the group of people available to contribute to the assessment of Diploma related work. In the short term there is a need for a HSST working group to work with the MSC team and the RCPath in developing the curriculum and assessment tools but this may be shortlived. Membership of the TDE will comprise:

a. Chair b. Secretary c. Diploma co-ordinator d. HSST lead e. CPD co-ordinator f. Journal based learning co-ordinator g. MSC link h. Meetings organiser; this will involve organising an annual single day Diploma level meeting and one 2 day meeting to serve the needs of final year Diploma trainees/STP graduates/ new HSST trainees. They would liaise with the RE as necessary i. BSHI Diploma trainee representative j. Higher Specialist trainee representative k. 4 ordinary members

2. The RE membership will stay as it is and enhance its involvement it BSHI conference programme planning and contribute to the programme for training meetings 3.

The BEB will comprise a chairperson, secretary (the BSHI secretary), chair of TDE, chair of RE, secretary of RE, TDE Diploma co-ordinator, TDE HSST lead, chair RCPath panel of examiners, IBMS representative, BSHI representative to ACS, UK member of EFI education committee (should probably be co-opted because there may not always be a UK member of EFI education committee). Previous BEB membership comprised 10 members plus up to two co-opted members and the above changes have not affected the total membership.

Susan Martin, Chair, BSHI Education Board End

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British Society for Histocompatibility and Immunogenetics

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British Society for Histocompatibility and Immunogenetics

CHAIN meeting report David McKenzie/Victoria Robertson The Caledonian Histocompatibility and Immunogenetics Network (CHAIN) was formed with the aim of ensuring that H&I Laboratories across Scotland are able to deliver effective services for patients in organ, tissue and cell transplantation, transfusion and diagnostics. National Services Division of NHS Scotland has approved the establishment of CHAIN under its Managed Services project and is providing administrative support to develop CHAIN.

The inaugural meeting of CHAIN was held in Glasgow on the 10th October, 2011. The Victorian elegance of the Corinthian Club was the venue for the meeting centred on “The Clinical Relevance of Allosensitisation”. Delegates gathered from Scotland, Northern Ireland, and the North East of England, and included H&I scientists, surgeons, representatives from BSHI and NHS Education for Scotland and commercial suppliers.

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CHAIN meeting report continued Miss Laura Buist, Director and Lead Consultant for Transplantation, Glasgow Renal and Transplant Unit, opened the meeting by outlining the role and function of a network in H&I. Highlighting the aptness of the acronym CHAIN, she spoke of the benefits a network can bring in delivering team working, uniformity of approach and in driving forward developments in H&I to enhance clinical practice across Scotland. Mr Derek Bishop, the Network Lead of the Scottish Pathology Network (SPAN), a collaborative group consisting of all NHS Pathology services in Scotland, then shared the experience of the SPAN. SPAN’s achievements have included the delivery of electronic image sharing and remote reporting, as well as collaboration in the requisitioning of new equipment. Benchmarking and the analysis of activity have enabled laboratories to learn from each other and have promoted efficiency to the benefit of the service. SPAN has played a key role in securing Government support for initiatives to develop services, such as tumour DNA testing to predict responses to therapy. Derek identified the key factors in SPAN’s success as Pathology ownership, Government buy‐ in, providing patient benefits, delivering service change and redesign and improving quality. The rest of the morning was devoted to an educational session on HLA antibodies, in which Craig Taylor, Marc Clancy and Rob Higgins gave expert accounts of relevant HLA antibodies, the surgeon’s perspective and the modulation of HLA antibodies after antibody incompatible transplantation (AIT) respectively. Dr Craig Taylor, H&I Consultant Clinical Scientist at Addenbrooke’s Hospital, Cambridge, discussed the relevance of allosensitisation, specifically the role of HLA‐specific antibodies in solid organ transplantation. Craig started his presentation highlighting that hyperacute

rejection has been listed as a “Never Event” by the Department of Health as the technology is now available to prevent this. Whilst CDC and flow crossmatching are key tools in assessing the safety of a transplant, it is the CHAIN meeting report David McKenzie/Victoria Robertson Page 1 of 6 advent of single antigen beads and Luminex technology which has driven a revisit of the dogma surrounding antibodies. The clinical significance of antibodies was reviewed in terms of timings (should historical samples still be considered?), antibody class (IgM vs IgG), antibody specificity and antibody strength. Finally, the impact of Luminex single antigen bead technology in the identification of de novo donor specific antibodies, which are associated with poor outcomes, was also reviewed. Mr Marc Clancy, Transplant Surgeon, Glasgow Renal and Transplant Unit, then gave a renal surgeon’s perspective on transplantation. Marc gave a comprehensive overview of the practicalities of transplantation, including the increasing demand for transplantation and the benefits it brings, surgical procedures, immunosuppressive protocols and post‐transplant complications. The aim is to perform a transplant with acceptable immunological risk, informed by advice from the H&I laboratory and clinical colleagues. Risks need to be explained to and accepted by the patient. Immediate and early complications can include bleeding, thrombosis, wound infections and ureteric leaks. Few patients have a smooth path after transplantation, with common problems including delayed graft function, acute rejection, side‐ effects of immunosuppressive drugs and infections, though many of these initial problems resolve within the first few months post‐transplant. Chronic allograft nephropathy remains the main cause of

graft failure with increasing evidence for the involvement of donor‐specific antibodies. Finally, Marc described developments in surgical techniques, antibody removal and paired and pooled donation that are benefitting patients. By the end of his talk Marc had achieved his aim of convincing us that surgeons really are nice people and encouraged the audience to approach and interact with surgical colleagues. Dr Rob Higgins, Consultant Nephrologist, Coventry, then spoke of his centre’s experience of the modulation of HLA antibodies in over 100 renal transplants after antibody‐incompatible transplantation (AIT). After describing the process of antibody removal by double filtration plasmapheresis and transplant outcomes, Rob spoke in some detail about the kinetics of antibody production after AIT. There is an immediate post‐transplant decrease in donor‐specific antibody (DSA), followed by an increase and a subsequent decrease. Kinetics of antibody production and removal can be expressed as antibody half‐life and doubling time. In responsive patients, whose peak post‐transplant DSA was 20% higher than pre‐treatment levels, the doubling time was not associated with the starting DSA level, but the half‐life of decay was strongly associated with late DSA levels. Modulation of HLA antibodies is normal, especially in patients whose DSA levels peak earlier, and may be long lasting. However there is a period of 5 – 6 days when the graft is at risk because of high antibody levels. Antibody may be absorbed by the graft, so at Rob’s centre treatment is guided by creatinine levels and biopsy results rather than by antibody levels alone. Post‐transplant treatment is by ATG or OKT3 rather than plasmapheresis. Following the three talks there were questions from the audience and

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British Society for Histocompatibility and Immunogenetics

CHAIN meeting report continued

discussion of the differences of approach between centres. The networking theme continued over lunch in the Corinthian’s Brasserie, where delegates were encouraged to mix and become better acquainted with their colleagues. After lunch a series of case studies were presented from the Belfast, Edinburgh, Glasgow and Newcastle H&I laboratories. For the opening case presentation, Helen McFarlane from Glasgow discussed the identification of a rare HLA‐DP allele, HLA‐DPB1*64:01N in a renal patient following a failed transplant. This rare allele was registered with the Allele Frequency Net Database (www. allelefrequencies.net) and highlighted the importance of considering rare alleles

when determining patient HLA types. David McKenzie, also from Glasgow, described the case of a Goodpasture’s syndrome patient with an unexplained antibody screening reaction and inconclusive single antigen bead Luminex assay. No test issues could be identified and it was hypothesized that these unexplained results may be due to the patient’s autoimmune condition. This case highlights some potential limitations of the current technology. In the third case presentation, Stephanie Cairns from Edinburgh discussed the prozone effect in single antigen bead testing for the detection of HLA‐specific antibodies. A prozone effect can be observed when the concentration of the antibody(‐ies) is high and inhibits its own

detection. In the context of single antigen bead testing, dilution or the addition of EDTA to the sample in five patients led to the detection of antibodies not previously identified suggestive of a prozone effect. The impact of this effect may be clinically significant both in the pre‐ and post‐ transplant setting. The second presentation from Edinburgh was by Angie Abel on the Fluogene, a new fluorescence‐based gel electrophoresis‐ free PCR‐SSP system. This new system aims to reduce the time taken to generate an HLA type in the out‐of‐hours setting by nearly one hour therefore contributing to an overall reduction in organ allocation time. Bernie Magee from Belfast discussed the clinical relevance of donor‐specific

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British Society for Histocompatibility and Immunogenetics

CHAIN meeting report continued antibodies, illustrating this with the case of a renal transplant patient with an HLA‐ A11 specific antibody who received a transplant from a donor expressing HLA‐ A11. The graft survived 11 years indicating that whilst the patient had a donor‐ specific antibody, this antibody was not immediately detrimental to the graft. This raises important questions over which antibodies are clinically relevant and which detection method should be used to define this as for this patient the cross‐match by complement‐dependent cytotoxicity was negative but was positive by flow cytometry. The final case study was presented by Fotini Partheniou from Newcastle. Fotini’s presentation discussed the case of a 6‐month old baby girl with hypoplastic left heart listed for transplant. As part of the pre‐transplant workup, three unacceptable HLA‐specific antibodies – HLA‐DQ7, ‐DP2, ‐DP3 – were identified. A donor heart was offered six days after listing; the donor was HLA‐DP2 and ‐DP3 positive. Plasma exchange was carried out peri‐transplant, however DSAs rose post‐transplant but the patient remained well. The role of HLA‐DP but also ‐DQ antibodies in cardiothoracic transplants is not yet clear which is supported by the findings presented by Fotini. The case presentations were very well received and highlighted the diversity and challenges of H&I work but also the technological advances which have changed H&I.

Claire Burt and Claire Cryer provided an overview of their training as clinical scientists in H&I in Scotland. They discussed the similarities and differences in working practices across the different H&I laboratories in Scotland as well as detailing the activities of each of these laboratories. The guest lecture was given by Dr Paul Shiels, Senior Lecturer in Transplantation, University of Glasgow, on his work on biomarkers of ageing for use in transplantation. One such marker is telomere length which is predictive of mortality to an accuracy of about 5 years. telomere shortening is increased in the presence of disease. This is seen in patients with chronic renal disease who have shorter telomeres, more DNA deamination and more inflammation (increased IL‐6). The use of older donors for transplantation is increasing but biological age may be a better predictor of outcome than chronological age. Paul’s group have examined if post‐transplant renal function correlates with markers of biological age by measuring markers of cellular damage and biological age in pre‐ implantation biopsies. Serum creatinine levels at 6 months and 1 year were associated with donor age, urinary protein to creatinine ratios, CDKN2A levels and telomere length, with CDKN2A levels and donor age together accounting for about 40% of the observed variation in creatinine. Markers of biological age can be tested by PCR in about 3 – 4 hours, making this feasible in routine transplantation, permitting early intervention when risk is increased. Increased biological age is associated with socioeconomic factors such as low income and poor diet, and the group is involved in the study of psychological, social and biological determinants of ill health in Glasgow, where disparities in socioeconomic status are particularly marked.

In a concluding discussion, Prof Phil Dyer, H&I Director, Scottish National Blood Transfusion Service, Edinburgh, thanked the speakers, meeting organisers and NHS Education Scotland and commercial partners for their support. Suggestions for projects for the next year included a survey of services provided by H&I labs in Scotland and their research interests, the development of a website, harmonisation of working practices including common procedures for listing unacceptable antigens for transplantation, shared validation of new technologies and audit. The meeting was considered a great success and plans are underway for a second meeting next year in Edinburgh.

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British Society for Histocompatibility and Immunogenetics

Dear Colleagues It gives me great pleasure to invite you to participate in the joint conference of: - International HLA and Immunogenetics Workshop Conference - 26th European Immunogenetics and Histocompatibility Conference (EFI) - 23rd British Society of Histocompatibility and Immunogenetics Conference (BSHI) Abstract submission is now open Abstract Submission Deadline: 1st February 2012 An outline programme and abstract submission details can be found on the web site. The preliminary programme for the workshop is also available on the web site. http://ihiwefibshi.org/

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British Society for Histocompatibility and Immunogenetics

12th One Lambda European Clinical Workshop 21st-24th June 2011, Dubrovnik Jessica Ward, Trainee Clinical Scientist, NHSBT Filton While staying in Dubrovnik in 1929, George Bernard Shaw said: “If you want to see heaven on earth, come to Dubrovnik”. This popular Croatian city a UNESCO World Heritage Site situated on the Adriatic Sea was host to the 12th One Lambda European Clinical Workshop. Fifteen kilometers North West of the beautiful walled city is the stylish Radisson Blu Resort which provided the perfect backdrop for the workshop. A host of fifty international scientists, One Lambda representatives and distributors converged to primarily share practical experiences of emerging technologies and techniques. The workshop also provided an international forum for participants to discuss strategies employed by laboratories to overcome difficulties with current methods. I was lucky enough to have

been selected to receive the 2011 VH Bio bursary in order to attend the workshop and present my BSHI diploma research project, an exciting yet daunting privilege. Upon arrival we were treated to a welcome cocktail and an al fresco dinner at the hotel giving everyone a chance to meet prior to the first session. The workshop began the following day with an introduction and welcome from George Ayoub, CEO One Lambda. The session was then opened by Dr. Henny Otten of the Netherlands who gave an insightful talk on the clinical relevance of Luminex-defined complement fixing HLAantibodies in kidney transplantation. This theme continued throughout the fist session. Anne Cesbron-Gautier (France) concluded that the risk to develop acute antibody mediated rejection (AAMR) in kidney transplantation is not better associated with donor specific antibody

(DSA) identification by SA C1q than by SA IgG. However, the absence of DSA C1q is more predictive of the non occurrence of AAMR. The study also showed an interest in SA C1q in the monitoring of DSA in post-transplant in kidney recipients since DSA C1q often disappeared following several plasmapheresis sessions whereas DSA IgG were still present. Other conclusions from this session supported the hypothesis of the harmful effect of complement-fixing HLA DSA on kidney graft outcome and that C1q-positive DSA, even if present at low LSA-IgG MFI values, determined restriction in transplant access due to positive CDC/FC crossmatch results (D. Caputo, Italy). C Schonemann (Germany) suggested that the estimation of the cytotoxic potential of Luminex detectable HLA antibodies would contribute to formulate an individual immunological risk score for organ transplant candidates.

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British Society for Histocompatibility and Immunogenetics

12th One Lambda..... continued Following the daytime sessions the group was sailed by a historical galleon style boat to one of the nearby Elaphiti Islands. Here the group enjoyed a roof-terrace lunch followed by some free time to explore the beautiful island.

The second session began with Luis Ramalhete (Portugal) presenting three cases relating to patient-specific antibodies (PSA’s) highlighting issues with the LSA kit and suggesting the C1q kit may resolve such cases. This session also included a talk concluding that intragraft DSA detection could constitute an additional marker of actively evolving graft lesions with a humoral immune component (J-L Taupin, France). Following the daytime sessions the group was taken for lunch in the historic city followed by a tour of city’s beautiful streets and monuments. There was also a chance for those willing to brave the afternoon sun to walk the two kilometers of city walls. The evening speaker for Wednesday was Dr Milagros Samaniego, Michigan USA who talked about the challenges and goals associated with screening for de novo DSA’s. The presentation highlighted the need for long term/multi centre study and the need for guidelines and standardisation prior to mainstream participation. Cost implications and timescale required to see the impact of any early intervention made following antibody detection were also discussed. Thursday’s morning session was opened by Nancy Reinsmoen, Los Angeles, California. This presentation focused on

the role of antibody assessment riskstratification of HLA specific antibodies in heart and lung transplantation. Problems arising from antigen density on beads not reflecting that on cells, calculated PRA and virtual crossmatching were all discussed. Other talks in this session included the use of Luminex technology to enable transplant of a hypersensitised patient following a decrease in MFI of donor HLA antibodies following desensitisation with IA and i.v. Igs (M. Lopez-Hoyos). Derek O’Neill (Ireland) presented an evaluation of the single antigen screening assays with regard to establishing a ‘cut-off’ that would define clinically relevant antibodies. Concluding that both One Lambda and Genprobe kits were capable of generating spurious positives and the use of both Luminex methods proved useful in defining ‘windows’ in a patients’ antibody profile. During the next session a report from V. Dubois (Switzerland) presented two AML cases where pre-transplant HLA mistyping due to acquired uniparental disomy was detected. Dr Katy Latham, UK reported a significant increase in donor recruitment to the Anthony Nolan registry following a change in recruitment strategy to saliva collections for new volunteers. Other presentations included an interesting look at trends in the cord blood bank (G. Sanchez, Spain).

The evening talk on Thursday was delivered by Dr. Robert Higgins (UK) who presented some of his experience of how HLA antibodies behave after transplantation of pre-sensitised patients. The presentation also included snapshots and brief descriptions of some of the more charismatic wild birds of the UK ensuring everyone was fully alert following an afternoon of sunshine. Friday’s session were opened by Dr. Manuela Testi (Italy) who reported on the definition of a new strategy to solve ambiguities in high resolution HLA class I typing. High definition Labtype kits have enabled large batching of samples and therefore a faster turnaround in HLA typing for the Rome transplant network with low levels of ambiguity. During this session came my turn to present my project evaluating the use of a One Lambda kit and Luminex technology to detect and identify HNA antibodies. Although a daunting prospect I was put at ease by the warm and friendly welcome I had received throughout the workshop. This final session was closed by Dr. Paul Terasaki who reminded us of the great advances made to date in the journey of histocompatibility and immunnogenetics. Following this session the group retired in order to prepare for the Gala dinner. The evening was hosted at the stunning Sponza Palace. With its mixture of late Gothic and Renaissance styles the palace provided a wonderful setting for an evening of music, dining and the closing of a very informative and culturally insightful workshop. The good weather and beautiful surroundings provided an added bonus. End

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British Society for Histocompatibility and Immunogenetics

BSHI 29 BSHI Volume 85 – 2012 Issue 4 Š2012 The British Society for Histocompatibility & Immunogenetics

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Newsletter 85  

British Society for Histocompatibility and Immunogenetics Newsletter

Newsletter 85  

British Society for Histocompatibility and Immunogenetics Newsletter

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