Gras Julien, Nere Marie Laure, Peraldi Marie Noëlle, Bonnet-Madin Lucie, Salmona Maud, Taupin Jean Luc, Desgrandchamps François, Verine Jérôme, Brochot Etienne, Amara Ali, Molina Jean Michel, Delaugerre Constance
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.
Transpl Infect Dis. 2023 Apr;25(2):e14012. doi: 10.1111/tid.14012. Epub 2023 Feb 7.
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.
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.
At the time of BKVN diagnosis, BKV viral load was 8.2 log IU/10 cells and 5.4 log 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.
Altogether, our data suggest that among some KTR with BKVN, the BKV genotype from the donor may not be responsible for BKVN pathogenesis.
在患有BK病毒相关性肾病（BKVN）的肾移植受者（KTR）中，BK病毒基因型的演变和抗BK病毒体液反应尚未完全明确。我们旨在分析移植后BK病毒的复制和基因演变，并描述伴随的抗BK病毒VP1体液反应。
我们回顾性分析了32例经活检证实的BKVN病例。对储存的血浆和肾活检组织进行BK病毒载量检测，并对阳性样本进行VP1测序。在移植时和诊断为BKVN时测定BKV-VP1基因型特异性中和抗体（NAbs）滴度。
在诊断为BKVN时，肾组织和血浆中的BK病毒载量分别为8.2 log IU/10细胞和5.4 log IU/mL。VP1测序在31/32例病例的两个样本中鉴定出相同的BK病毒亚型。在移植时，20份活检样本中有8份（40%）检测出BK病毒阳性，而同时期的BK病毒血症为阴性。在这些样本中的5/6中，VP1测序鉴定出与BKVN不同的亚型。移植后得到证实：8例患者在出现BK病毒血症之前肾活检为BK病毒阳性，且VP1测序在所有这些患者中均鉴定出与BKVN不同的亚型。在BK病毒血症出现后且在诊断为BKVN之前，BK病毒阳性血浆和肾活检中的BK病毒亚型与在BKVN时分离出的亚型相同。与移植时相比，BKVN时BKV-VP1 NAbs滴度显著更高（p = 0.0031），各基因型的滴度相似。
总体而言，我们的数据表明，在一些患有BKVN的KTR中，供体的BK病毒基因型可能与BKVN的发病机制无关。
