Short-term Immunopathological Changes Associated with Pulse Steroids/IVIG/Rituximab Therapy in Late Kidney Allograft Antibody Mediated Rejection.
Short-term Immunopathological Changes Associated with Pulse Steroids/IVIG/Rituximab Therapy in Late Kidney Allograft Antibody Mediated Rejection.
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DOI：
10.34067/kid.0001082019
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发表时间：
2020-05
期刊：
影响因子：
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通讯作者：
Djamali A
中科院分区：
文献类型：
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作者：
Degner KR;Wilson NA;Reese SR;Parajuli S;Aziz F;Garg N;Mohamed M;Singh T;Mandelbrot DA;Panzer SE;Redfield RR;Van Hyfte K;Zhong W;Hidalgo LG;Djamali A
B细胞耗竭是抗体介导的排斥反应（ABMR）的常见治疗方法。我们试图确定这种治疗方法在肾移植中的特异性免疫病理学作用。这是一项对诊断为晚期ABMR（移植后>3个月）的肾移植受者的前瞻性观察研究。患者接受脉冲类固醇，IVIG和利妥昔单抗治疗。在基线和3个月时评估供体特异性HLA抗体（DSA）、肾移植病理学、肾功能、免疫细胞表型和47种循环细胞因子。我们在2015年4月至2019年3月期间入组了23例患者。大多数患者为男性（74%）和白人（78%），平均年龄为45.6±13.8岁。在移植后6.8±5.9年（4个月-25年）诊断出ABMR。与基线相比，治疗与循环HLA I类DSA（P=0.003）和II类DSA（P=0.002）以及肾小管周围毛细血管炎（ptc，P=0.04）显著下降相关。血清肌酐、BUN、eGFR和蛋白尿（UPC）保持稳定。循环B细胞消耗至几乎不可检测的水平（P≤0.001），而BAFF（P=0.001）、APRIL（P<0.001）和IL-10（P=0.02）水平在治疗后显著增加。值得注意的是，循环CD 4+（P=0.02）和CD 8 + T细胞（P=0.003）显著升高。我们还注意到循环细胞毒性CD 8 + T细胞与BAFF（P=0.05）、调节性T细胞与IL 10（P=0.002）和HLA I类DSA（P=0.005）之间存在显著相关性。短期脉冲类固醇/IVIG/利妥昔单抗治疗与ABMR（DSA和ptc）抑制、肾功能稳定以及调节性B细胞和T细胞存活细胞因子增加相关。需要进一步的研究来了解B细胞耗竭对调节ABMR的T细胞、B细胞和体液成分之间的串扰的影响。
B-cell depletion is a common treatment of antibody-mediated rejection (ABMR). We sought to determine the specific immunopathologic effects of this therapeutic approach in kidney transplantation. This was a prospective observational study of kidney transplant recipients diagnosed with late ABMR (>3 months after transplant). Patients received treatment with pulse steroids, IVIG, and rituximab. Donor specific HLA antibodies (DSA), kidney allograft pathology, renal function, immune cell phenotypes, and 47 circulating cytokines were assessed at baseline and at three months. We enrolled 23 patients in this study between April 2015 and March 2019. The majority of patients were male (74%) and Caucasian (78%) with an average age of 45.6±13.8 years. ABMR was diagnosed at 6.8±5.9 years (4 months-25 years) post-transplant. Treatment was associated with a significant decline in circulating HLA class I DSA (P=0.003) and class II DSA (P=0.002) and peritubular capillaritis (ptc, P=0.04) compared to baseline. Serum creatinine, BUN, eGFR, and proteinuria (UPC) remained stable. Circulating B-cells were depleted to barely detectable levels (P≤0.001), whereas BAFF (P=0.001), APRIL (P<0.001), and IL-10 (P=0.02), levels increased significantly post-treatment. Notably, there was a significant rise in circulating CD4+ (P=0.02) and CD8+ T-cells (P=0.003). We also noted a significant correlation between circulating cytotoxic CD8+ T-cells and BAFF (P=0.05), regulatory T-cells and IL10 (P=0.002), and HLA class I DSA (P=0.005). Short-term pulse steroids/IVIG/rituximab therapy was associated with inhibition of ABMR (DSA and ptc), stabilization of kidney function, and increased regulatory B-cell and T-cell survival cytokines. Additional studies are needed to understand the implications of B cell-depletion on the crosstalk between T-cells, B-cells, and humoral components that regulate ABMR.