Human leukocyte antigen typing and crossmatch: A comprehensive review

Abstract

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.

Expression profile of HLA‐B*38:55Q allele

“…Serological methods, such as CDC microlymphocitotoxicity test and CDC‐XM with multiple polyclonal antibodies displaying anti HLA‐B38 specificity, failed to reveal the presence of the HLA‐B*38:55Q protein on the cell's surface. In addition to the standard microlymphocytotoxicity test, we analyzed the cell surface expression by means of flow cytometry (FCXM), a more sensitive and specific method, using three patient sera containing polyclonal antibodies directed against HLA‐B38. To investigate the hypothesis that the Cys101 substitution causes a temperature‐sensitive alteration, the antigen expression was studied at room temperature and 37°C.…”

Long-Term Outcomes among Kidney Transplant Recipients and after Graft Failure: A Single-Center Cohort Study in Brazil

“…As expected, and similar to that previously observed, acute rejection was the cause of earlier graft loss, with more than 60% of events occurring within the first year. However, there was a small impact on the cohort (2.2%), reflecting the improvement in the quality of immunosuppression observed in the last decades and more sensitive techniques of pretransplant immunological evaluation [31–34]. Despite this, it should be considered that late acute rejection loss still accounts for 1/3 of the losses in this category, reflecting other possible variables that have gained considerable interest in the recent transplantation era, such as adherence to immunosuppressive therapy [35, 36].…”

Epigenetički biomarkeri u presađivanju bubrega

“…Pozitivna križna proba imunološka je reakcija uzrokovana vezanjem ljudskih leukocitnih antigena (engl. human leukocyte antigen; HLA) izraženih na stanicama presatka sa specifičnim antitijelima HLA u serumu primatelja 10 . Zbog povezanosti donorspecifičnih antitijela (engl.…”