Non-HLA antibodies in transplantation: when do they matter?
A growing interest in the contribution of non-human leukocyte antigens (non-HLA) antibodies to allograft rejection has led to the identification of multiple target antigens and investigation into the possible mechanisms of injury. Although several non-HLA antibody specificities have been identified, the largest cohorts studied are those detected using commercial assays. This review focuses on the phenotypes of injury associated with non-HLA antibody and defines in-vivo environmental characteristics that may be conducive to non-HLA antibody-mediated injury.



Mechanistic studies in animal models and clinical data suggest that an inflammatory environment, increased antigen expression, and development of neoantigens through posttranslational modifications contribute to non-HLA antibody development and their subsequent contribution to allograft injury. Furthermore, many reports show worse outcomes when HLA and non-HLA antibodies are present, suggesting possible interactions between these antibodies that lead to increased injury. Plasmapheresis and intravenous immunoglobulin are currently used to reduce HLA and non-HLA antibodies; however, therapeutic strategies targeting B cells and plasma cells simultaneously may lead to more durable antibody elimination.



Immune triggers that lead to non-HLA antibody formation are complex and poorly understood. The ability of non-HLA antibodies to mediate allograft injury may depend upon their specificity and affinity, density of the target antigen, and synergy with HLA antibodies.
Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.
Mary Carmelle
MC
Philogene
Annette M
AM
Jackson
D006680:HLA Antigens / Q000276:immunology*; D006801:Humans; D007518:Isoantibodies / Q000276:immunology*; D023001:Transplantation Tolerance / Q000276:immunology*; D014184:Transplantation, Homologous / Q000379:methods*
D006680:HLA Antigens; D007518:Isoantibodies