Antibodies to Non-HLA Antigens and Their Role in Organ Transplant Rejection

Antibody-mediated rejection (AMR) is a serious post-transplant complication that is associated with a worse prognosis of survival of transplanted organs. The diagnosis of AMR is based on clinical, pathological characteristics and on the detection of antibodies specific to the organ donors' mismatched human leukocyte antigens (HLA) antigens. Accumulating evidence in recent years however suggests that antibodies against antigens encoded by genes outside the HLA complex can play a role in the development of AMR. Non-HLA antigens are mostly expressed on the surface of endothelial and epithelial cells but can also be localized intracellularly and released in the bloodstream or lymph in case of cell lysis. Among these are major histocompatibility complex (MHC) Class I-related chain MICA, MICB, angiotensin II-R1 receptor (ATR1), collagen, K-α1 tubulin, cardiac myosin, vimentin and other molecules. Antibodies to non-HLA antigens can occur before transplantation but may be also produced de novo. The detection of non-HLA antibodies is carried out using the xMap (Luminex) technology, the so-called endothelial crossmatch and other techniques; however, these methodologies and interpretation of results have their pitfalls. In this short review, we briefly discuss the recent literature on the clinical role of non-HLA antibodies in organ transplant rejection and survival.