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

Julien Gras (1, 2, 3) , Marie Laure Nere (1) , Marie Noëlle Peraldi (4, 1) , Lucie Bonnet-Madin (2, 1, 3) , Maud Salmona (4, 1) , Jean Luc Taupin (4, 1) , François Desgrandchamps (4, 1) , Jérôme Verine (1) , Etienne Brochot (5) , Ali Amara (2, 1, 3) , Jean Michel Molina (1, 2, 3) , Constance Delaugerre (2, 1, 3)

1 AP-HP - Hopital Saint-Louis [AP-HP]
2 GenCellDis (U944 / UMR7212) - Génomes, biologie cellulaire et thérapeutiques
3 IRSL - Institut de Recherche Saint-Louis - Hématologie Immunologie Oncologie (Département de recherche de l’UFR de médecine ; ex- Institut Universitaire Hématologie-IUH)
4 UPCité - Université Paris Cité
5 Laboratoire de Virologie [CHU Amiens]

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 log10 IU/106 cells and 5.4 log10 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.

Mots clés: kidney transplantation; BK virus; BKV associated nephropathy; genetics; humoral response

Domaines: Médecine humaine et pathologie

Julien Gras, Marie Laure Nere, Marie Noëlle Peraldi, Lucie Bonnet-Madin, Maud Salmona, et al.. BK virus genotypes and humoral response in kidney transplant recipients with BKV associated nephropathy. Transplant Infectious Disease, 2023, ⟨10.1111/tid.14012⟩. ⟨hal-03980734⟩