APHP (Assistance Publique-Hôpitaux de Paris), Hôpital H. Mondor-A. Chenevier, Centre d'Investigation Clinique Biothérapie, Créteil, France.
Université Paris-Est, UMR_S955, UPEC, Créteil, France.
Front Immunol. 2020 Jan 24;11:34. doi: 10.3389/fimmu.2020.00034. eCollection 2020.
High dose intravenous immunoglobulin (IVIG) are widely used after kidney transplantation and its biological effect on T and B cell phenotype in the context of maintenance immunosuppression was not documented yet. We designed a monocentric prospective cohort study of kidney allograft recipients with anti-HLA donor specific antibodies (DSA) without acute rejection on screening biopsies treated with prophylactic high-dose IVIG (2 g/kg) monthly for 2 months. Any previous treatment with Rituximab was an exclusion criterion. We performed an extensive analysis of phenotypic and transcriptomic T and B lymphocytes changes and serum cytokines after treatment (day 60). Twelve kidney transplant recipients who completed at least two courses of high-dose IVIG (2 g/kg) were included in a median time of 45 (12-132) months after transplant. Anti-HLA DSA characteristics were similar before and after treatment. At D60, PBMC population distribution was similar to the day before the first infusion. CD8 CD45RA T cells and naïve B-cells (Bm2) decreased ( = 0.03 and = 0.012, respectively) whereas Bm1 (mature B-cells) increased ( = 0.004). RORγt serum mRNA transcription factor and CD3 serum mRNA increased 60 days after IVIG ( = 0.02 for both). Among the 25 cytokines tested, only IL-18 serum concentration significantly decreased at D60 ( = 0.03). In conclusion, high dose IVIG induced limited B cell and T cell phenotype modifications that could lead to anti-HLA DSA decrease. However, no clinical effect has been isolated and the real benefit of prophylactic use of IVIG after kidney transplantation merits to be questioned.
高剂量静脉注射免疫球蛋白（IVIG）在肾移植后广泛应用，但在维持性免疫抑制的情况下，其对 T 细胞和 B 细胞表型的生物学作用尚未得到证实。我们设计了一项单中心前瞻性队列研究，纳入了在筛查活检中无急性排斥反应且存在抗 HLA 供体特异性抗体（DSA）的肾移植受者，这些受者在移植后接受预防性高剂量 IVIG（2 g/kg）每月 2 次，共 2 个月。任何以前使用利妥昔单抗的治疗均为排除标准。我们对治疗后（第 60 天）T 和 B 淋巴细胞表型和血清细胞因子的变化进行了广泛分析。12 例完成至少 2 个疗程高剂量 IVIG（2 g/kg）治疗的肾移植受者纳入研究，中位时间为移植后 45 个月（12-132 个月）。治疗前后抗 HLA DSA 特征相似。在第 60 天，PBMC 群体分布与首次输注前一天相似。CD8 CD45RA T 细胞和幼稚 B 细胞（Bm2）减少（=0.03 和 =0.012），而 Bm1（成熟 B 细胞）增加（=0.004）。RORγt 血清转录因子和 CD3 血清 mRNA 在 IVIG 后 60 天增加（两者均=0.02）。在测试的 25 种细胞因子中，只有 IL-18 血清浓度在第 60 天显著降低（=0.03）。总之，高剂量 IVIG 诱导了有限的 B 细胞和 T 细胞表型改变，可能导致抗 HLA DSA 减少。然而，尚未分离出临床效果，预防性使用 IVIG 后肾移植的真正获益值得质疑。
