Alloimmunity and autoimmunity in chronic rejection.
OBJECTIVE
Recent studies demonstrate an increasing role for alloimmune responses in the disruption of self-tolerance leading to immune responses to self-antigens that play a role in the immunopathogenesis of chronic rejection following solid organ transplantation. This review summarizes recent studies and implications for the alloimmune-response-induced de-novo development of autoimmune responses following solid organ transplantations.


RESULTS
Immediately following organ transplantation, several factors lead to enduring an inflammatory milieu. Studies from our laboratory and others have demonstrated that development of antihuman leukocyte antigen antibodies precedes the development of chronic rejection. Using an in-vivo murine model, we have demonstrated that administration of anti-major histocompatibility complex (MHC) class I directly into the native lungs leads to chronic rejection pathology. Further, the in-vitro ligation of epithelial cell surface MHC class I molecules by specific anti-MHC can lead to cell activation and production of fibrinogenic growth factors.


CONCLUSIONS
On the basis of these findings, we hypothesized that alloimmune responses can lead to autoimmunity, thus playing an important role in chronic rejection. Characterization of both the temporal occurrence and functional significance of antibodies to self-antigens may provide insight into the pathogenesis of chronic rejection and these antibodies can serve as clinically useful biomarkers.
Seetharam
Anil
A
Division of Gastroenterology, Department of Surgery, Washington University School of Medicine, 660 S. Euclid Avenue, St. Louis, MO 63110, USA.
Tiriveedhi
Venkataswarup
V
Mohanakumar
T
T
D000818:Animals; D015551:Autoimmunity; D002908:Chronic Disease; D006084:Graft Rejection / Q000276:immunology* / Q000517:prevention & control; D006085:Graft Survival; D006801:Humans; D007111:Immunity, Cellular; D056724:Immunity, Humoral; D007165:Immunosuppression Therapy / Q000379:methods; D018836:Inflammation Mediators / Q000378:metabolism; D016377:Organ Transplantation / Q000009:adverse effects*; D023001:Transplantation Tolerance; D014184:Transplantation, Homologous; D016896:Treatment Outcome
D018836:Inflammation Mediators