Cioni Michela, Muscianisi Stella, De Cicco Marica, Basso Sabrina, Hirsch Hans H, Fontana Iris, Catenacci Laura, Bagnarino Jessica, Siciliano Mariangela, Montana Lampo Oriana, Acquafredda Gloria, Boti Lou Tina Diana, Rotella Jessica, Bozza Eleonora, Zumelli Jennifer, Mebelli Kristiana, Baldanti Fausto, Cardillo Massimo, Zecca Marco, Nocera Arcangelo, Luppi Mario, Verrina Enrico, Ginevri Fabrizio, Comoli Patrizia
Fondazione Malattie Renali del Bambino, IRCCS G. Gaslini Institute, 16147 Genova, Italy.
Transfusion Service, IRCCS G. Gaslini Institute, 16147 Genova, Italy.
Microorganisms. 2024 Dec 30;13(1):48. doi: 10.3390/microorganisms13010048.
Polyomavirus BK (BKPyV)-associated nephropathy (BKPyV-nephropathy) remains a significant cause of premature kidney allograft failure. In the absence of effective antiviral treatments, current therapeutic approaches rely on immunosuppression (IS) reduction, possibly at the risk of inducing alloimmunity. Therefore, we sought to explore the long-term effects of a tailored viro-immunologic surveillance and treatment program for BKPyV on the development of alloimmunity and kidney graft outcome. Forty-five pediatric kidney transplant recipients were longitudinally monitored for BKPyV replication, virus-specific immunity, and donor-specific HLA antibodies (DSAs). DNAemia developed in 15 patients who were treated with stepwise IS reduction. Among the other 30 patients, 17 developed DNAuria without DNAemia and 13 always resulted as BKPyV-negative. All patients with DNAemia cleared BKPyV after having mounted a virus-specific cellular immune response, and no biopsy-proven BKPyV-nephropathy was observed. The presence of cytotoxic populations directed to the BKPyV Large-T (LT) antigen early after transplantation protected kidney recipients from developing BKPyV replication, and the appearance of LT-specific T cells in viruric patients prevented the development of BKPyV-DNAemia. In our cohort, no significant correlation was observed between BKPyV-DNAemia and the development of DSA and antibody-mediated rejection. However, patients who experienced and cleared BKPyV-DNAemia had a worse allograft survival at a median follow-up of 18.9 years ( = 0.048). These data need to be confirmed in larger cohorts.
多瘤病毒BK（BKPyV）相关性肾病（BKPyV肾病）仍是肾移植过早失败的一个重要原因。在缺乏有效抗病毒治疗的情况下，目前的治疗方法依赖于降低免疫抑制（IS），但这可能有诱发同种免疫的风险。因此，我们试图探讨针对BKPyV的定制化病毒免疫监测和治疗方案对同种免疫发展和肾移植结局的长期影响。对45名儿童肾移植受者进行了纵向监测，观察BKPyV复制、病毒特异性免疫和供体特异性HLA抗体（DSA）情况。15名接受逐步降低IS治疗的患者出现了病毒血症。在其他30名患者中，17名出现了无病毒血症的病毒尿，13名一直检测为BKPyV阴性。所有出现病毒血症的患者在产生病毒特异性细胞免疫反应后均清除了BKPyV，且未观察到经活检证实的BKPyV肾病。移植后早期针对BKPyV大T（LT）抗原的细胞毒性群体的存在可保护肾移植受者不发生BKPyV复制，病毒血症患者中LT特异性T细胞的出现可防止BKPyV病毒血症的发生。在我们的队列中，未观察到BKPyV病毒血症与DSA的产生及抗体介导的排斥反应之间存在显著相关性。然而，经历并清除BKPyV病毒血症的患者在中位随访18.9年时移植肾存活率较低（P = 0.048）。这些数据需要在更大的队列中得到证实。
