Role of HLA C7 in BKV Infections

Abstract

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). However, the retrospective design with limited cases, lack of controls, lack of description of immunosuppression regimen and absence of analysis of the data make their observations difficult to interpret. Of note, we found that slightly less than 50% of all our recipients and donors were HLA C7 positive, rather than 24% which Awadallah et al. (1), reported as the prevalence in Caucasians. If their Caucasian transplant population had such a low frequency, then chisquared analyses of the data show that the presence of HLA C7 in the recipient would be associated with BKV nephropathy in recipients (12 of 23 patients (53%), p = 0.002) and the presence of HLA C7 in the donors would be associated with a trend toward BKV nephropathy in the recipients (6 of 13 patients, (46%), p = 0.06). We did not observe any BKV nephropathy in our prospective, intensely monitored study because of protocol-driven preemptive withdrawal of the anti-metabolite component of the maintenance immunosuppressive regimen. Nevertheless, their findings do not negate or contradict our own. They are just different. It is conceivable that factors such as excessive immunosuppression could have overridden any protective effect of HLA C7. Thus, we agree with the assertion that the natural history of BKV can be modulated. We have shown prospectively that a strategy of frequent monitoring and judicious pre-emptive reduction in immunosuppression prevented overt BKV nephropathy in all our recipients and prevented sustained BK viremia in all but a select group, those without HLA C7.