HLA Susceptibility to BKV Infection

Abstract

We read with interest the article by Bohl et al. titled 'Donor origin of BK virus in renal transplantation and role of HLA C7 in susceptibility to sustained BK viremia' (Am J Transplant 2005; 5: 2213-2221. The authors' observations on the HLA C7 locus prompted us to examine the HLA typing data on our own patients with BKV nephropathy, who presented 11 ± 6.8 months after transplantation. On a retrospective review, data on HLA Cw loci were available in 31 recipients (23 Caucasians, 8 African Americans), of which 14 (45%) patients (12 Caucasians, 2 African Americans) typed as HLA C7. Donor HLA type was available for 16 patients (13 Caucasians, 3 African Americans), and 7 (44%) (6 Caucasians, 1 African American) carried an HLA C7 allele. By comparison, HLA-Cw7 is reported in 24% of healthy Caucasian subjects. Bohl et al.'s study noted absence of HLA C7 in 10 of 11 recipients with BK viremia, and 11 of 11 donors were also HLA C7 negative. Our data indicate that absence of HLA C7 is neither required nor a sufficient condition for the development of BKV nephropathy. The relationship between HLA genotype and the natural history of infection can presumably be modulated by other parameters such as the degree of immunosuppression, presence of specific cytokine gene polymorphisms, and participation by both innate and acquired immunity. It should be noted that the patients described by Bohl et al. represent self-limited episodes of BKV viremia, whereas our patients developed biopsy proven nephropathy.

Characterization of Immunodominant BK Polyomavirus 9mer Epitope T Cell Responses

“…Because BKPyV-specific T cell responses are %50to 100-fold lower than those to cytomegalovirus, these assays have not readily entered clinical practice. Moreover, the risk factors for BKPyV replication and nephropathy vary in different KT studies and include steroid pulses for acute rejection, maintenance immunosuppression such as tacrolimus-mycophenolate versus cyclosporine-mycophenolate, older age of recipients, male sex and a higher number of HLA mismatches (37)(38)(39)(40)(41)(42)(43)(44)(45). According to the recent Organ Procurement and Transplantation Network and Scientific Registry of Transplant Recipients report, these risk factors are present in a substantial number of KT patients (46).…”

“…According to the recent Organ Procurement and Transplantation Network and Scientific Registry of Transplant Recipients report, these risk factors are present in a substantial number of KT patients (46). Moreover, organs from BKPyV IgG-positive donors for recipients with low or undetectable antibodies may face an increased risk (34)(35)(36)(37)(38)(39)(40)(41)(42)(43)(44)(45)(46)(47)(48).…”

“…We and others investigated cellular immune responses to overlapping peptide pools encoded in the early viral gene region (EVGR) or the late viral gene region (LVGR) of the BKPyV DNA genome . T cell responses to the LVGR-encoded capsid viral protein VP1 were generally more pronounced than those to EVGR-encoded viral proteins (30)(31)(32)(33)(34)(35)(36)(37)(38)(39)(40)(41)(42)(43)(44)(45)(46)(47)(48)(49). Interferon c (IFN-c) responses were largely derived from CD4 + T cells and, to a lesser extent, from CD8 + T cells .…”

Role of HLA C7 in BKV Infections

“…We found the study by Awadallah et al (1), to be provocative in that it showed that the presence of the MHC class I allele, HLA C7, was not sufficient to prevent BKV nephropathy in renal transplant recipients. The authors state that this contrasts with our own study showing that persistent BK viremia correlated with the absence of HLA C7 (2).…”

BK Polyomavirus and the Transplanted Kidney

“…Matching of HLA-A2, B44, and DR15 may be protective against BK viremia, 84 and the absence of C7 in either the donor or the recipient may be a risk factor for BK infection, 17 a result that was not confirmed in another cohort. 85 …”