TY - JOUR
T1 - Non-HLA antibodies in transplantation
T2 - When do they matter?
AU - Philogene, Mary Carmelle
AU - Jackson, Annette M.
N1 - Publisher Copyright:
© 2016 Wolters Kluwer Health, Inc. All rights reserved.
PY - 2016/8/1
Y1 - 2016/8/1
N2 - Purpose of review 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. Recent findings 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. Summary 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.
AB - Purpose of review 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. Recent findings 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. Summary 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.
KW - Allograft rejection
KW - antibody-mediated rejection
KW - non-HLA antibody
KW - transplantation
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U2 - 10.1097/MOT.0000000000000335
DO - 10.1097/MOT.0000000000000335
M3 - Review article
C2 - 27258575
AN - SCOPUS:84973542714
SN - 1087-2418
VL - 21
SP - 427
EP - 432
JO - Current opinion in organ transplantation
JF - Current opinion in organ transplantation
IS - 4
ER -