BK virus genotypes and humoral response in kidney transplant recipients with BKV associated nephropathy

Background: Among kidney transplant recipients (KTR) with BK virus associated nephropathy (BKVN), BKV genotypes' evolution and anti-BKV humoral response are not well established. We aim to analyze BKV replication and genetic evolution following transplantation, and characterize concomitant anti-BKV-VP1 humoral response.Methods: We retrospectively analyzed 32 cases of biopsy-proven BKVN. Stored plasma and kidney biopsies were tested for BKV viral load, and VP1 sequencing performed on positive samples. BKV-VP1 genotype-specific neutralizing antibodies (NAbs) titers were determined at transplantation and BKVN.Results: At the time of BKVN diagnosis, BKV viral load was 8.2 log(10)IU/10(6) cells and 5.4 log(10)IU/mL in kidney and plasma, respectively. VP1 sequencing identified the same BKV-subtype in both compartments in 31/32 cases. At the time of transplantation, 8/20 (40%) of biopsies tested positive for BKV detection, whereas concomitant BKV viremia was negative. VP1 sequencing identified a different subtype compared to BKVN in 5/6 of these samples. This was confirmed following transplantation: 8 patients had a BKV+ biopsy before BKV viremia, and VP1 sequencing identified a different subtype compared to BKVN in all of them. After the onset of BKV viremia and prior to BKVN diagnosis, the BKV subtype in BKV+ plasma and kidney biopsy was the same as the one isolated at BKVN. BKV-VP1 NAbs titers were significantly higher at the time of BKVN compared to transplantation (p = .0031), with similar titers across genotypes.Conclusion: Altogether, our data suggest that among some KTR with BKVN, the BKV genotype from the donor may not be responsible for BKVN pathogenesis.

Automated summary

This study analyzed the evolution of BK virus genotypes and the humoral response against BK virus in kidney transplant recipients with BK virus associated nephropathy. The results showed that BK virus replicated and genetically evolved following transplantation, and the level of anti-BK-VP1 antibodies also increased. The study suggests that the BK virus genotype from the donor may not be responsible for the pathogenesis of BK virus associated nephropathy in some patients.