Chong Stephanie M Y, Hung Rachel K Y, Yuen Chang Fernando, Atkinson Claire, Fernando Raymond, Harber Mark, Magee Ciara N, Salama Alan D, Reeves Matthew
University College London Institute of Immunity and Transplantation, Royal Free Hospital, London, UK.
Kings College London, London, UK.
EBioMedicine. 2024 Dec;110:105430. doi: 10.1016/j.ebiom.2024.105430. Epub 2024 Nov 15.
BK polyomavirus (BKV) DNAaemia occurs in 10% of recipients of kidney transplants, contributing to premature allograft failure. Evidence suggests disease is donor derived. Hypothetically, recipient infection with a different BKV serotype increases risk due to poorer immunological control. Thus, understanding the composition and activity of the humoral anti-BKV responses in donor/recipient (D/R) pairs is critical.
Using 224 paired pre-transplant D/R samples, BKV VP1 genotype-specific pseudoviruses were employed to define the breadth of the antibody response against different serotypes (ELISA) and, to characterise specific neutralising activity (nAb) using the 50% inhibitory concentration (LogIC50). Mismatch (MM) ratios were calculated using the ratio of recipient ELISA or nAb reactive BKV serotypes relative to the number of donor reactive serotypes.
BKV DNAaemia was observed in 28/224 recipients of kidney transplants. These recipients had lower nAb titres against all the serotypes, with median logIC50 values of 1.19-2.91, compared to non-viraemic recipients' median logIC50 values of 2.13-3.30. nAb D/R MM ratios >0.67 associated with significantly higher risk of BKV viraemia, with an adjusted odds ratio of 5.12 (95% CI 2.07 to 13.04; p < 0.001). Notably, a mismatch against donor serotype Ic and II associated with adjusted odds ratios of 8.12 (95% CI 2.10 to 35.61; p = 0.002) and 4.52 (95% CI 1.19 to 19.23; p = 0.03) respectively. 21 recipients demonstrated broadly neutralising responses against all the serotypes, none of whom developed BKV DNAaemia post-transplant. In contrast, there was poor concordance with PsV-specific ELISA data that quantified the total antibody response against different serotypes.
BKV nAb mismatch predicts post-transplant BKV DNAaemia. Specific mismatches in nAb, rather than total seroreactivity, are key indicators of BKV risk post-transplant. This has the potential to risk-stratify individuals and improve clinical outcomes by influencing the frequency of monitoring and individualised tailoring of immunosuppression. Furthermore, detailed examination of individuals with broadly neutralising responses may provide future therapeutic strategies.
The research was funded by St. Peters Trust, Royal Free Hospital Charity and Wellcome Trust (grant numbers RFCG1718/05, SPT97 and 204870/Z/WT_/Wellcome Trust/United Kingdom).
BK多瘤病毒（BKV）血症在10%的肾移植受者中出现，导致移植肾过早失功。有证据表明该疾病源自供体。据推测，受者感染不同的BKV血清型会因免疫控制较差而增加风险。因此，了解供体/受者（D/R）对中体液抗BKV反应的组成和活性至关重要。
使用224对移植前D/R样本，采用BKV VP1基因型特异性假病毒来确定针对不同血清型的抗体反应广度（酶联免疫吸附测定法），并使用50%抑制浓度（LogIC50）来表征特异性中和活性（中和抗体）。错配（MM）比率通过受者酶联免疫吸附测定法或中和抗体反应性BKV血清型与供体反应性血清型数量的比率来计算。
在224例肾移植受者中有28例观察到BKV血症。与非病毒血症受者的中位LogIC50值2.13 - 3.30相比，这些受者针对所有血清型的中和抗体滴度较低，中位LogIC50值为1.19 - 2.91。中和抗体D/R MM比率>0.67与BKV病毒血症风险显著升高相关，调整后的优势比为5.12（95%置信区间2.07至13.04；p < 0.001）。值得注意的是，与供体血清型Ic和II错配分别与调整后的优势比8.12（95%置信区间2.10至35.61；p = 0.002）和4.52（95%置信区间1.19至19.23；p = 0.03）相关。21例受者对所有血清型均表现出广泛的中和反应，其中无一例在移植后出现BKV血症。相比之下，与量化针对不同血清型的总抗体反应的假病毒特异性酶联免疫吸附测定数据的一致性较差。
BKV中和抗体错配可预测移植后BKV血症。中和抗体的特定错配而非总血清反应性是移植后BKV风险的关键指标。这有可能对个体进行风险分层，并通过影响监测频率和免疫抑制的个体化调整来改善临床结果。此外，对具有广泛中和反应的个体进行详细检查可能会提供未来的治疗策略。
该研究由圣彼得斯信托基金、皇家自由医院慈善机构和惠康信托基金资助（资助编号RFCG1718/05、SPT97和204870/Z/WT_/惠康信托基金/英国）。
