Copyright ©The Author(s) 2017. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Transplant. Dec 24, 2017; 7(6): 339-348
Published online Dec 24, 2017. doi: 10.5500/wjt.v7.i6.339
Human leukocyte antigen typing and crossmatch: A comprehensive review
Mohammed Mahdi Althaf, Mohsen El Kossi, Jon Kim Jin, Ajay Sharma, Ahmed Mostafa Halawa
Mohammed Mahdi Althaf, Jack Pryor Renal Unit, Norfolk and Norwich University Hospital - NHS Foundation Trust, Norwich NR4 7UY, United Kingdom
Mohammed Mahdi Althaf, Mohsen El Kossi, Jon Kim Jin, Ajay Sharma, Ahmed Mostafa Halawa, Faculty of Health and Science, University of Liverpool, Institute of Learning and Teaching, School of Medicine, Liverpool L69 3GB, United Kingdom
Mohsen El Kossi, Doncaster Royal Infirmary, Doncaster DN2 5LT, United Kingdom
Jon Kim Jin, Nottingham Children Hospital, Nottingham NG7 2UH, United Kingdom
Ajay Sharma, Royal Liverpool University Hospitals, Liverpool L7 8XP, United Kingdom
Ahmed Mostafa Halawa, Department of Transplantation Surgery, Sheffield Teaching Hospitals, Sheffield S5 7AU, United Kingdom
Author contributions: Althaf MM performed the majority of the writing, prepared the figures and tables; Sharma A performed input to structure, content and wrote the abstract; El Kossi M and Jin JK performed input to content; Halawa AM designed the outline, performed input to content and coordinated the writing of the paper.
Conflict-of-interest statement: There is no conflict of interest associated with any of the senior author or other co-authors contributed their efforts in this manuscript.
Open-Access: This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See:
Correspondence to: Ahmed Mostafa Halawa, MSc, MD, PGCE, MEd (Higher Education), FRCS, FRCS (Gen), Senior Lecturer (Hon), Consultant Transplant Surgeon, Department of Transplantation Surgery, Sheffield Teaching Hospital, Herries Road, Sheffield S5 7AU, United Kingdom.
Telephone: +44-77-87542128 Fax: +44-11-42714604
Received: July 12, 2017
Peer-review started: July 14, 2017
First decision: August 7, 2017
Revised: August 22, 2017
Accepted: October 17, 2017
Article in press: October 17, 2017
Published online: December 24, 2017

Renal transplantation remains the best option for patients suffering from end stage renal disease (ESRD). Given the worldwide shortage of organs and growing population of patients with ESRD, those waitlisted for a transplant is ever expanding. Contemporary crossmatch methods and human leukocyte antigen (HLA) typing play a pivotal role in improving organ allocation and afford better matches to recipients. Understanding crossmatch as well as HLA typing for renal transplantation and applying it in clinical practice is the key step to achieve a successful outcome. Interpretation of crossmatch results can be quite challenging where clinicians have not had formal training in applied transplant immunology. This review aims to provide a worked example using a clinical vignette. Furthermore, each technique is discussed in detail with its pros and cons. The index case is that of a young male with ESRD secondary to Lupus nephritis. He is offered a deceased donor kidney with a 1-0-0 mismatch. His complement dependent cytotoxicity (CDC) crossmatch reported positive for B lymphocyte, but flow cytometry crossmatch (FCXM) was reported negative for both B and T lymphocytes. Luminex-SAB (single antigen bead) did not identify any donor specific antibodies (DSA). He never had a blood transfusion. The positive CDC-crossmatch result is not concordant with DSA status. These implausible results are due to underlying lupus erythematosus, leading to false-positive B-lymphocyte crossmatch as a result of binding immune complexes to Fc-receptors. False positive report of CDC crossmatch can be caused by the underlying autoimmune diseases such as lupus erythematosus, that may lead to inadvertent refusal of adequate kidney grafts. Detailed study of DSA by molecular technique would prevent wrong exclusion of such donors. Based on these investigations this patient is deemed to have “standard immunological risk” for renal transplantation.

Keywords: Human leukocyte antigen typing, Cytotoxic crossmatch, Flow cytometry crossmatch, Virtual crossmatch, Human leukocyte antigen null alleles

Core tip: Understanding crossmatch for renal transplantation and applying it in clinical practice is the fundamental step to achieve a successful outcome. At times, interpreting an ambivalent report of crossmatch can be very challenging for clinicians since they have not been trained formally in applied transplant immunology. While there are several published reviews, this is presented as a worked example and is aimed to discuss immunological risk stratification by using an example of an index case.