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 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.

Conclusion

Altogether, our data suggest that among some KTR with BKVN, the BKV genotype from the donor may not be responsible for BKVN pathogenesis.

     

血栓弹力图评价抗血小板药物疗效对颅内外动脉支架术后再狭窄的影响

目的分析血栓弹力图仪（TEG）检测颅内外动脉支架置人术（PTAS）后患者服用阿司匹林和氯吡格雷后血小板聚集的抑制率，了解其疗效对PTAS术后支架内再狭窄（ISR）的影响。方法收集颅内外动脉TAS术后因缺血性中风复发或者术后6～12个月常规行脑动脉数字减影血管造影（DSA）随访且行TEG检测的49例患者（64处病变血管）的临床资料。根据DsA结果分为ISR组和对照组（无ISk），比较两组间的各种血管病危险因素、血清超敏C反应蛋白（hs-CRP）水平、花生四烯酸（AA）途径和腺苷二磷酸（ADP）受体途径诱导血小板抑制率间的差异，探讨影响ISR形成的因素。结果（1）卒中复发组与无复发组比较：复发组（男：女=1：5）与无复发组（男：女=39：4）组间性别组成的差异有统计学意义（P〈0．01）；复发组血清hs—CRP水平显著高于无复发组[（8．9±11．0）VS（2．9±4．1）mg／L，P〈0．05]；而其余各变量间差异均无统计学意义（P〉0．05）。（2）ISR兰且与对照组比较：ISR组患病年龄显著小于对照组[（58．0±12．8）VS（64．6±9．8）岁；P〈0．051；两组间糖尿病患者的比例差异具有统计学意义（P〈0．05）；ISR-C-R颅内外支架再狭窄比例（6／14VS8／14）与对照组（7／50VS43／50）间的差异有统计学意义（P〈0．05）；IS咄血清hs—CRP浓度显著高于对照组[（6．1±7．6）VS（2．1±2．1）mg／L，P=0．028]；ISR组AA和ADP平均抑制率分别为（58．0±43．8）％和（28．1±26．1）％，显著低于对照组的（83．4±23．1）％和（52．8±29．5）％（均P〈0．01）。（3）Logistic~归分析显示，在校正了其他因素的影响后，仅ADP抑制率（氯吡格雷疗效）与ISR的形成呈负相关（HR=0．959；95％C10．921～0．998；P：0．039）。结论氯吡格雷抗血小板聚集的疗效与ISR的形成呈负相关，即氯吡咯雷抵抗在ISR的形成中起非常重要的作用。