Guidelines for the detection and characterisation of ... · PDF filecharacterisation of clinically relevant antibodies in ... John Smith PhD FRCPath, ... clinically relevant antibodies

Version 4.0 Revised January 2016
Guidelines for the detection and characterisation of clinically relevant
antibodies in allotransplantation

Guidelines for the detection and characterisation of
clinically relevant antibodies in allotransplantation
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A collaborative publication by:
British Society for Histocompatibility & Immunogenetics Executive Business Support Ltd, City Wharf, Davidson Road, Lichfield, Staffordshire WS14 9DZ Company No: 6078396 Registered in England and Wales, Registered Charity No: 1123760
www.bshi.org.uk
and
British Transplantation Society South Park Road, Macclesfield, Cheshire SK11 6SH Company No: 4691176 Registered in England and Wales, Registered Charity No: 1098584
www.bts.org.uk
Publication at www.bshi.org.uk & www.bts.org.uk
January 2016
Based upon a search of publications in December 2013 Revision due December 2016
The British Society for Histocompatibility & Immunogenetics (BSHI) is the professional body for healthcare and academic scientists supporting clinical transplantation and transplantation research. The British Transplantation Society (BTS) is the professional body for surgeons, physicians, specialist nurses for organ donation, nurses, healthcare scientists, allied health professionals and scientists actively working in clinical transplantation and transplantation research.
http://www.bshi.org.uk/http://www.bts.org.uk/http://www.bshi.org.uk/http://www.bts.org.uk/

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Disclaimer:
These Guidelines are guides to best practice, which inevitably change with the passage of
time. All practitioners need to undertake clinical care on an individual basis and keep
themselves up to date with changes in practice of clinical medicine. The British
Transplantation Society and The British Society for Histocompatibility & Immunogenetics
Guidelines ("the Guidelines") were compiled by a joint working party of the Societies. The
Guidelines represent the collective opinions of a number of experts in the field and do not
have the force of law. The Guidelines contain information and guidance for use by
practitioners as a best practice tool; it follows that the Guidelines should be interpreted as
such. The opinions presented in the Guidelines are subject to change and should not be
considered to be a treatment recommendation for any individual patient.
The British Transplantation Society and The British Society for Histocompatibility & Immunogenetics cannot attest to the accuracy, completeness or currency of the opinions and information contained herein and does not accept any responsibility or liability for any loss or damage caused to any practitioner or any third party as a result of any reliance being placed on the Guidelines or as a result of any
inaccurate or misleading opinion contained in the Guidelines.

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CONTENTS Page
1 ABBREVIATIONS .............................................................................................................. 5
2 PROCESS OF GUIDELINE DEVELOPMENT .......................................................... 6
3 THE EVIDENCE BASE..................................................................................................... 7
4 WRITING COMMITTEE ................................................................................................... 8
5 RECOMMENDATIONS AND BEST PRACTICE ................................................. 12
6 INTRODUCTION .............................................................................................................. 17
7 DEFINING RISK............................................................................................................... 24
8 IDENTIFICATION OF HLA SPECIFIC ANTIBODIES ......................................... 26
9 DEFINITION OF UNACCEPTABLE ANTIGENS ................................................... 35
10 CROSSMATCHING ...................................................................................................... 39
11 KIDNEY and PANCREAS TRANSPLANTATION ............................................. 44
12 ISLET TRANSPLANTATION .................................................................................... 53
13 THORACIC ORGAN TRANSPLANTATION ....................................................... 55
14 LIVER TRANSPLANTATION ................................................................................... 61
15 INTESTINAL and MULTI-VISCERAL TRANSPLANTATION ....................... 65
16 HLA-SPECIFIC ANTIBODY INCOMPATIBLE TRANSPLANTATION ........ 67
17 HAEMATOPOIETIC PROGENITOR CELL TRANSPLANTATION........... 71
18 APPENDICES ............................................................................................................. 73

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1 ABBREVIATIONS
AMR Antibody Mediated Rejection BSHI British Society for Histocompatibility & Immunogenetics BOS Bronchiolitis Obliterans Syndrome BTS British Transplantation Society CAV Cardiac Allograft Vasculopathy CBU Cord Blood Unit CDC Complement Dependent Cytotoxicity cRF Calculated Reaction Frequency DSA Donor-specific HLA antibodies DTT Dithiothreitol ELISA Enzyme Linked Immnunosorbent Assay FCXM Flow Cytometry Crossmatch HCPC Health and Care Professions Council MFI Mean Fluorescence Intensity NHSBT-ODT NHS Blood and Transplant Organ Donation and Transplantation PRA Panel Reactive Antibodies TCR T Cell Receptor PAK Pancreas After Kidney PTA Pancreas Transplant Alone SPK Simultaneous Pancreas and Kidney

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2 PROCESS OF GUIDELINE DEVELOPMENT
The histocompatibility laboratory is now able to define the presence of HLA specific
antibodies with a high degree of sensitivity, resulting in on-going re-definition of the
crossmatch boundary to allow the successful transplantation of allosensitised patients. The
introduction of solid phase assays led to the publication of the 2004 and later the 2010
Guidelines. Subsequently, technological developments continued allowing relative
quantification of HLA specific antibody levels which, combined with crossmatching results
allowed a graded assessment of the immunological risk should a transplant proceed, rather
than a simple positive or negative crossmatch assessment. This facilitated the
establishment and growth of HLA antibody incompatible living donor kidney transplantation.
Recent developments and experience have prompted a further update of these Guidelines,
so that optimum approaches can be applied to maximise safe and effective use of the
donor organ pool.
These Guidelines are written from the standpoint of ABO blood group compatible
transplantation and focus upon HLA-specific antibodies in both deceased and living donor
allotransplantation. ABO and HLA antibody incompatible kidney transplantation are covered
in a separate document:
(http://www.bts.org.uk/Documents/Guidelines/Active/AiT%20guidelines%20Jan%202011%2
0FINAL.pdf). This revision of the Guidelines includes a new chapter describing the role of
HLA antibodies in haematopoietic stem cell transplantation.
http://www.bts.org.uk/Documents/Guidelines/Active/AiT%20guidelines%20Jan%202011%20FINAL.pdfhttp://www.bts.org.uk/Documents/Guidelines/Active/AiT%20guidelines%20Jan%202011%20FINAL.pdf

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3 THE EVIDENCE BASE
The authors drew the evidence to support their recommendations from peer-reviewed
publications up to December 2013. The specialist nature of histocompatibility testing in the
context of clinical allotransplantation means that there are few large or multicentre studies
in this field and meta analyses are not frequent, but these have been referenced when
possible. Furthermore, recent changes in technology to detect and define HLA specific
sensitisation have made many historic publications less relevant or obsolete.
The recommendations are graded according to three levels following the principles outlined
in the Consensus Guidelines on the Testing and Clinical Management Issues Associated
with HLA and Non HLA Antibodies in Transplantation (Tait B et al, Transplantation 2013;
95: 19-47).
Level 1 Indicates guidance based on conclusions from peer-reviewed published data and currently proven practice
Level 2 Indicates guidance based on a consensus opinion of the authors but where
there is insufficient published evidence to support practice. Level 3 Indicates a recommendation in the absence of direct evidence but where the
authors agree there may be benefit.

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4 WRITING COMMITTEE
Executive bodies from the BSHI and the BTS invited the persons