Antihuman leukocyte antigen antibody-induced autoimmunity: role in chronic rejection.
OBJECTIVE
We provide evidence for the role of de-novo development of immune responses to self-antigens in the posttransplant period and its possible induction by alloimmunity in the pathogenesis of chronic rejection following lung, heart and kidney transplantation. The present review details recent findings for the two distinct yet interdependent immune processes in the immunopathogenesis of chronic rejection.


RESULTS
The contribution of both humoral and cell-mediated alloimmune responses against mismatched donor histocompatibility antigens (HLA) in the pathogenesis of chronic rejection is well established. Recent studies have focused on development of immune responses to self-antigens during the posttransplant period and its correlation with chronic rejection. These self-antigens include myosin and vimentin in cardiac, K-alpha-1-tubulin and collagen-V in lung and angiotensin II type 1 receptor, collagen-IV and VI in kidney transplants. During the posttransplant period, the development of immune responses to self-antigens is facilitated by induction of a distinct subset of autoreactive T-helper cells referred to as Th17 cells.


CONCLUSIONS
Following organ transplantation, tissue injury and remodeling inflicted by antibodies (Abs) to HLA antigens is conducive to develop autoimmunity. Abs to HLA and self-antigens are detectable in the serum of transplant recipients who develop chronic rejection. Anti-HLA Abs are often present transiently but precede the development of Abs to self-antigens.
Nath
Dilip S
DS
Division of Cardiothoracic Surgery, Washington University School of Medicine, St Louis, Missouri 63110, USA.
Basha
Haseeb Illias
HI
Mohanakumar
Thalachallour
T
D000818:Animals; D001323:Autoantibodies / Q000097:blood; D001324:Autoantigens / Q000276:immunology; D015551:Autoimmunity; D002908:Chronic Disease; D006084:Graft Rejection / Q000276:immunology*; D006085:Graft Survival; D006680:HLA Antigens / Q000276:immunology*; D006801:Humans; D007111:Immunity, Cellular; D056724:Immunity, Humoral; D007518:Isoantibodies / Q000097:blood*; D016377:Organ Transplantation / Q000009:adverse effects*; D023001:Transplantation Tolerance; D016896:Treatment Outcome
D001323:Autoantibodies; D001324:Autoantigens; D006680:HLA Antigens; D007518:Isoantibodies