Negative Impact of Human Leukocyte Antigen Matching in the Outcome of Polyomavirus Nephropathy

Abstract

Factors dependent on the host, the virus, and the allograft affect the course of polyomavirus allograft nephropathy (PVAN). Development of specific cytotoxic antiviral immunity requires recognition of host human leukocyte antigen (HLA) molecules together with viral peptides on the target cells. We correlated the number of matched HLA-A, HLA-B, and HLA-DR antigens with graft outcome in 90 patients with PVAN. Patients that maintained graft function had significantly less degrees of HLA matching (mean 1.5) in comparison to patients with graft loss (mean 2.87, P= 0.001). Markedly reduced incidence of graft loss was observed in patients with no HLA matching whatsoever in comparison to patients with any degree of matching (P= 0.003). Lack of HLA matching may impair the host's ability to mount an effective antiviral cytotoxic immune response. An adequately developed antiviral cellular immunity may lead to significant tissue damage and graft loss even if the viral infection is eventually controlled.

Acute Rejection

“…Although early reports suggested a link with Tacrolimus and mycophenolate-based regimens, it seems likely that the risk of BKVAN relates to the total burden of immunosuppression rather than to any specific drug (Rahamimov et al, 2003, Nickeleit et al, 2000a. Some authors reported that the injury of the renal allograft may have an important role in the pathogenesis of BKVAN (Drachenberg et al, 2005). The association found between human lymphocyte antigen mismatching and BKVAN supports the hypothesis (Awadalla et al, 2004).…”

BK Virus Nephropathy and Kidney Transplantation

“…The specificity of the cellular response may also be detrimental. Recipients with greater donor and recipient HLA mismatching had an increased incidence of BKV nephropathy (70), possibly mediated by more episodes of rejection, intense immunosuppression, and impaired cytotoxicity in an allogeneic environment but less allograft loss (71). This suggests that lysis of allogeneic BKV-infected target cells is less efficient with HLA-unrestricted T cells than with HLA-restricted T cells.…”

Virus-Induced Cellular Immune Mechanisms of Injury to the Kidney

“…Under immunosuppressive drug regimens that commonly are used to prevent rejection of kidney allografts by the host, reactivated BK virus can induce cytopathic and inflammatory injury to the renal epithelium that closely mimics rejection (20,21). One recent study found that during the tapering of immunosuppression to allow adaptive immune responses to mount against reactivated virus, allografts that were more closely matched to the host at MHC class I loci fared worse than those that were not as closely matched (22). This suggested that CTL responses were more effective at killing infected renal epithelial cells and paradoxically promoting a further loss of renal function in MHC class I-matched allografts with polyomavirus (22).…”

“…One recent study found that during the tapering of immunosuppression to allow adaptive immune responses to mount against reactivated virus, allografts that were more closely matched to the host at MHC class I loci fared worse than those that were not as closely matched (22). This suggested that CTL responses were more effective at killing infected renal epithelial cells and paradoxically promoting a further loss of renal function in MHC class I-matched allografts with polyomavirus (22). This is reminiscent of immune restoration inflammatory syndromes that can occur after initiation of antiretroviral therapy in HIV-infected patients, in which reconstituted adaptive immune responses to an existing burden of foreign antigen (e.g., from mycobacterium tuberculosis) can lead to inflammatory injury to organs, including to the kidney (23).…”