Schaenman Joanna, Rossetti Maura, Pickering Harry, Sunga Gemalene, Wilhalme Holly, Elashoff David, Zhang Qiuheng, Hickey Michelle, Reddy Uttam, Danovitch Gabriel, Reed Elaine F, Bunnapradist Suphamai
Division of Infectious Disease, Department of Medicine, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, California, USA.
Department of Pathology and Laboratory Medicine, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, California, USA.
Kidney Int Rep. 2022 Oct 20;8(1):126-140. doi: 10.1016/j.ekir.2022.10.015. eCollection 2023 Jan.
Belatacept has shown potential for prevention of rejection after kidney transplantation, given its demonstration of reduced nephrotoxicity in combination with absence of significant incidence of rejection. However, concerns have been raised regarding increased risk of viral infection.
We set out to explore the impact of the switch to belatacept on alloimmune and antiviral immunity through the study of patients switched from calcineurin inhibitor (CNI) to belatacept within 3 months of kidney transplantation compared with a matched cohort of control patients on a CNI-based regimen.
After the switch to belatacept, immune phenotyping demonstrated a decrease in naive and an increase in terminally differentiated effector memory (TMRA) T cells, with no significant difference compared with control patients. Donor-specific immune response, measured by intracellular cytokine staining (ICS), did not change significantly either by single or double cytokine secretion, but it was associated with the appearance of donor-specific antibody (DSA) in the control but not the belatacept cohort ( = 0.039 for naive and = 0.002 for TMRA subtypes). Increased incidence of DSA development was observed in the control group ( = 0.035). Virus-specific immune response, as measured by ICS in response to cytomegalovirus (CMV) or Epstein-Barr virus (EBV), was similar in both groups and stable over time.
We found that belatacept use was associated with an absence of alloreactivity without impact on immune phenotype, while preserving the antiviral immune response, for patients switched from a CNI-based regimen. In parallel, the antiviral immune response against CMV and EBV was preserved after the belatacept switch (clinicaltrials.gov: NCT01953120).
贝拉西普已显示出预防肾移植后排斥反应的潜力，因其与降低肾毒性相关且排斥反应发生率无显著增加。然而，人们对病毒感染风险增加表示担忧。
我们通过研究肾移植后3个月内从钙调神经磷酸酶抑制剂（CNI）转换为贝拉西普的患者，与接受基于CNI方案的匹配对照组患者队列相比，探讨转换为贝拉西普对同种异体免疫和抗病毒免疫的影响。
转换为贝拉西普后，免疫表型分析显示初始T细胞减少，终末分化效应记忆（TMRA）T细胞增加，与对照组患者相比无显著差异。通过细胞内细胞因子染色（ICS）测量的供体特异性免疫反应，无论是单一还是双细胞因子分泌，均无显著变化，但在对照组中与供体特异性抗体（DSA）的出现相关，而在贝拉西普组中则不然（初始亚型P = 0.039，TMRA亚型P = 0.002）。在对照组中观察到DSA发生率增加（P = 0.035）。通过ICS测量的针对巨细胞病毒（CMV）或EB病毒（EBV）的病毒特异性免疫反应在两组中相似且随时间稳定。
我们发现，对于从基于CNI方案转换过来的患者，使用贝拉西普与无同种异体反应性相关，且不影响免疫表型，同时保留抗病毒免疫反应。同时，转换为贝拉西普后，针对CMV和EBV的抗病毒免疫反应得以保留（clinicaltrials.gov：NCT01953120）。
