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BK virus genotypes and humoral response in kidney transplant recipients with BKV associated nephropathy |
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| Authors: | Julien Gras Marie Laure Nere Marie Noëlle Peraldi Lucie Bonnet-Madin Maud Salmona Jean Luc Taupin François Desgrandchamps Jérôme Verine Etienne Brochot Ali Amara Jean Michel Molina Constance Delaugerre |
| Affiliation: | 1. Infectious Disease Department, APHP-Saint-Louis Hospital, Paris, France;2. Virology Department, APHP-Saint Louis Hospital, Paris, France;3. Université Paris Cité, Paris, France Nephrology and Kidney Transplant Department, APHP-Saint Louis Hospital, Paris, France;4. INSERM U944, Biology of Emerging Viruses Team, Institut de Recherche Saint Louis, APHP-Saint-Louis Hospital, Paris, France;5. Université Paris Cité, Paris, France Virology Department, APHP-Saint Louis Hospital, Paris, France;6. Université Paris Cité, Paris, France;7. Université Paris Cité, Paris, France Urology Department, APHP-Saint Louis Hospital, Paris, France;8. Pathology Department, APHP-Saint Louis Hospital, Paris, France;9. Virology Department, CHU Amiens, Amiens, France;10. INSERM U944, Biology of Emerging Viruses Team, Institut de Recherche Saint Louis, APHP-Saint-Louis Hospital, Paris, France Université Paris Cité, Paris, France;11. Infectious Disease Department, APHP-Saint-Louis Hospital, Paris, France INSERM U944, Biology of Emerging Viruses Team, Institut de Recherche Saint Louis, APHP-Saint-Louis Hospital, Paris, France Université Paris Cité, Paris, France;12. INSERM U944, Biology of Emerging Viruses Team, Institut de Recherche Saint Louis, APHP-Saint-Louis Hospital, Paris, France Université Paris Cité, Paris, France Virology Department, APHP-Saint Louis Hospital, Paris, France |
| Abstract: | BackgroundAmong 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.MethodsWe 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.ResultsAt the time of BKVN diagnosis, BKV viral load was 8.2 log10IU/106 cells and 5.4 log10IU/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.ConclusionAltogether, our data suggest that among some KTR with BKVN, the BKV genotype from the donor may not be responsible for BKVN pathogenesis.
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| Keywords: | BK virus BKV associated nephropathy kidney transplantation genetics humoral response |