Guidelines for the detection and characterisation of ...

1 Version Revised June 2014 Guidelines for the detection and characterisation of clinically relevant antibodies in allotransplantation Guidelines for the detection and characterisation of clinically relevant antibodies in allotransplantation Page 2 of 94 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 and British Transplantation Society South Park Road, Macclesfield, Cheshire SK11 6SH Company No: 4691176 Registered in England and Wales, Registered Charity No.

2 1098584 Publication at & September 2014 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.

3 Guidelines for the detection and characterisation of clinically relevant antibodies in allotransplantation Page 3 of 94 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.

4 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 .

5 Guidelines for the detection and characterisation of clinically relevant antibodies in allotransplantation Page 4 of 94 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 .. 24 9 CROSSMATCHING .. 35 10 KIDNEY and PANCREAS TRANSPLANTATION .. 41 11 ISLET TRANSPLANTATION .. 51 12 THORACIC ORGAN TRANSPLANTATION .. 56 13 LIVER TRANSPLANTATION.

6 65 14 INTESTINAL and MULTI-VISCERAL TRANSPLANTATION .. 72 15 HLA-SPECIFIC ANTIBODY INCOMPATIBLE TRANSPLANTATION .. 77 16 HAEMATOPOIETIC PROGENITOR CELL 82 17 APPENDICES .. 87 Guidelines for the detection and characterisation of clinically relevant antibodies in allotransplantation Page 5 of 94 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 DBD Donation After Brain Stem Death DCD Donation After Circulatory Death DSA Donor-specific HLA antibodies DTT

7 Dithiothreitol ELISA Enzyme Linked Immunosorbent 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 Guidelines for the detection and characterisation of clinically relevant antibodies in allotransplantation Page 6 of 94 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.

8 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.

9 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: ( ). This revision of the Guidelines includes a new chapter describing the role of HLA antibodies in haematopoietic stem cell transplantation.

10 Guidelines for the detection and characterisation of clinically relevant antibodies in allotransplantation Page 7 of 94 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.