Antibodies Reactive to Non-HLA Antigens in Transplant Glomerulopathy

Abstract

Although T and B cell alloimmunity contribute to transplant injury, autoimmunity directed at kidneyexpressed, non-HLA antigens may also participate. Because the specificity, prevalence, and importance of antibodies to non-HLA antigens in late allograft injury are poorly characterized, we used a protein microarray to compare antibody repertoires in pre-and post-transplant sera from several cohorts of patients with and without transplant glomerulopathy. Transplantation routinely induced changes in antibody repertoires, but we did not identify any de novo non-HLA antibodies common to patients with transplant glomerulopathy. The screening studies identified three reactivities present before transplantation that persisted after transplant and strongly associated with transplant glomerulopathy. ELISA confirmed that reactivity against peroxisomal-trans-2-enoyl-coA-reductase strongly associated with the development of transplant glomerulopathy in independent validation sets. In addition to providing insight into effects of transplantation on non-HLA antibody repertoires, these results suggest that pretransplant serum antibodies to peroxisomal-trans-2-enoyl-coA-reductase may predict prognosis in kidney transplantation.

Association of Early Kidney Allograft Failure with Preformed IgA Antibodies to β 2-Glycoprotein I

“…33,34 Autoantibodies that have been associated with rejection in animal models may be important in allograft loss. However, their real role in humans is still insufficiently known.…”

“…However, their real role in humans is still insufficiently known. 35,36 Dinavahi et al 33 searched for autoantibodies (IgG isotype) against graft-expressed, non-HLA antigens, including B2GPI, and did not find aB2GPI antibodies. No IgA antibodies were included in their analysis.…”

B Cells, Antibodies, and More

“…These antibodies, usually against donor HLA but sometimes directed against non-HLA epitopes, are associated with poor renal allograft outcomes because of acute or chronic antibody-mediated rejection (AMR) (115)(116)(117)(118)(119). AMR is often associated with acute or chronic cellular rejection and the presence of DSAs also correlates with increased risk of isolated cellular rejection, indicating that DSAs are a useful biomarker for heightened antidonor immunity (120)(121)(122)(123)(124).…”

The Allo-Immunological Injury in Chronic Allograft Nephropathy

“…Persistent DSA or de novo development of DSA after kidney transplant is increasingly recognized as an independent and detrimental factor for transplant glomerulopathy. Other than allo-reactivity, there are emerging data suggesting that the preexisting or de novo developing autoimmunity, mediated by either auto-antibodies and/or autoreactive T cells, may also cause post-transplant allograft injury (Dinavahi et al, 2011;Porcheray et al, 2010;Vendrame et al,2010). Therefore, to appropriately identify and address the actual disease process, knowledge of the ongoing pathogenesis is needed in order to improve the long-term graft survival.…”

“…It has been recently suggested that the autoimmunity may also contribute to the post-transplant allograft injury (Dinavahi et al, 2011;Porcheray et al, 2010;Vendrame et al,2010). Here, we will focus our discussion on the allo-immunological injury, as this mechanism has been well established and its importance has been increasingly recognized in the pathogenesis of CAN.…”