Abstract
In this issue of the Journal, Binggeli and colleagues de-scribe a cross-sectional study of T-cell responses to 2 BKvirus (BKV) antigens correlated with plasma BKV load in42 kidney transplant recipients. Polyomavirus-associatednephropathy (PVAN) caused by BKV, or in rare cases, therelated JC virus, is one of the leading infectious causesof graft loss in renal transplantation. The consensus isthat BKV reactivation and disease in immunosuppressedpatients is largely associated with defects in cellular im-munity, and that BKV seropositivity prior to transplantationis inadequate to prevent viremia or PVAN (1). No corre-lation was found between plasma BKV levels and T-cellresponses to the VP1 capsid and large T (LT) antigen, afinding that differs from an earlier report that suggestedhigher VP1-specific responses correlated with elevatedBKV plasma load (2). However, Binggeli et al. report thatwhenthesubjectswereseparatedintotwogroupsaccord-ingtotherecentdynamicsoftheirplasmaBKVviremia,thegroup with decreasing BKV load had significantly higherT-cell responses to both viral antigens, although the datasuggested that the response to BKV-LT antigen was a bet-ter discriminator than the BKV-VP1 antigen for the groupwith falling virus load.The difficulties in conducting this type of cross-sectionalclinical immunology study are illustrated by an examinationof the history of immunosuppression in the 42 patients de-scribed in their report. One group of 20 subjects with de-creasing viral load included 7 individuals with historicallyresolved PVAN who were sampled at a much later timeafter transplant (mean of 231 days) compared with thosepatientswithoutahistoryofPVAN,andalsocontainedasig-nificant proportion (7/20) of individuals with reduced or noimmunosuppression. The other group of 22 patients withstableorincreasingBKVloadsincluded3subjectswhohadtheir immunosuppression increased and 3 in which it hadbeen decreased only within the prior 8 weeks. This chosentimeframe for consideration of alterations in immunosup-pression appears to be reasonable, given what is currentlyknown about the kinetics of BKV replication and clearancerates (3).Therapeutic tapering of immune suppression in responseto diagnosis of presumptive PVAN is currently the pri-mary mode of therapeutic intervention in many renal trans-plantation centers (1). The presumption is that reductionof immunosuppression, although increasing the risk ofallograft rejection, permits reconstitution of immune re-sponseswithconsequentclearanceofthevirus.Thisstudyextends prior evidence that tapering of immunosuppres-sion leads to an increase in BKV-specific T-cell responsesand reduction in viremia. Because of cost issues and re-sults indicating that shedding of BKV-infected decoy cellsprecedes BKV viremia and PVAN by several weeks (4,5),urine cytology is favored by some transplant centers asa screening test to detect BKV reactivation. However be-cause of its sensitivity and quantitative nature, PCR mea-surementofBKVloadinplasmaand/orurineevery2weeksis the recommended surrogate marker for monitoring viralresponse to therapy (1). Thus the findings of Binggeli et al.indicate that although plasma BKV load shows poor corre-lation with T-cell immune responses, the dynamics of viralload appear to reflect T-cell responses to two major viralantigens,andindicateaneedforserialPCRmeasurementsto guide clinical management of PVAN in renal transplantpatients. The subjects in this study were all seropositivefor both BKV and JCV, and the finding of comparable im-mune responses to JCV and BKV LT peptide libraries, butmore divergent responses to JCV and BKV VP1 peptidepools after
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