C1q-Fixing De Novo Donor Specific Antibodies in Therapeutic Management of Chronic Antibody-Mediated Rejection Postkidney Transplantation.

Masayuki Tasaki, Kazuhide Saito, Masahiro Ikeda, Yoshihiko Tomita
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Abstract

Backgrounds: Evidence for C1q-fixing donor-specific antibodies (DSA) after chronic antibody-mediated rejection (CABMR) treatment is lacking. We investigated if C1q-DSA could predict therapy response in patients with biopsy-proven CABMR.

Material and methods: Twenty kidney transplant patients with late-onset DSA were enrolled. Patients with biopsy-proven CABMR received three plasma pheresis sessions, one dose of rituximab (375 mg/m2), and steroid pulse therapy. We monitored IgG-DSA, C1q-DSA, and renal graft function for >2 years post-CABMR treatment. Patients with C1q-DSA mean fluorescence intensity (MFI) decreased by less than 50% post-treatment were classified as C1q-nonresponders. We compared Banff classification scores (g, ptc, cg, c4d) before and 6 months after treatment.

Results: Fourteen (70%) of 20 patients were C1q-DSA positive. The MFIs of IgG-DSA and C1q-DSA before treatment were significantly higher in the C1q-DSA positive group than in the negative group, at 20,035 and 10,918 (P = .008) and 17,702 and 21 (P < .001), respectively. Fifteen patients (75%) were diagnosed with CABMR via biopsy, and 12 patients received rejection therapy. Five (41.7%) patients were C1q-responders and seven (58.3%) were C1q-nonresponders. The MFIs of C1q-DSA before treatment were not significantly different between the two groups (11,521 vs. 13,985). Renal graft function was stable after treatment in C1q-responders for 3 years. In contrast, renal graft function tended to deteriorate in C1q-nonresponders. Biopsy showed improvement in scores in 75% of C1q-responders while deterioration in scores in 42.9% of C1q-nonresponders.

Conclusions: C1q-DSA may be a good predictor of outcomes after CABMR treatment.

C1q-固定新供体特异性抗体在肾移植后慢性抗体相关排斥反应治疗中的应用
背景:目前尚缺乏慢性抗体介导的排斥反应(CABMR)治疗后C1q固定供体特异性抗体(DSA)的证据。我们研究了 C1q-DSA 能否预测活检证实的 CABMR 患者的治疗反应:我们招募了 20 名晚期 DSA 肾移植患者。活检证实的 CABMR 患者接受了三次血浆置换治疗、一次利妥昔单抗剂量(375 毫克/平方米)和类固醇脉冲治疗。我们在CABMR治疗后的2年多时间里对IgG-DSA、C1q-DSA和肾移植功能进行了监测。治疗后 C1q-DSA 平均荧光强度 (MFI) 下降少于 50% 的患者被归类为 C1q 无应答者。我们比较了治疗前和治疗后 6 个月的 Banff 分类评分(G、PTC、CG、C4D):20名患者中有14名(70%)C1q-DSA阳性。治疗前,C1q-DSA 阳性组的 IgG-DSA 和 C1q-DSA 的 MFIs 明显高于阴性组,分别为 20,035 和 10,918 (P = .008) 以及 17,702 和 21 (P < .001)。15名患者(75%)通过活检确诊为CABMR,12名患者接受了排斥治疗。5名患者(41.7%)为C1q应答者,7名患者(58.3%)为C1q非应答者。两组患者治疗前的 C1q-DSA MFI 无明显差异(11521 对 13985)。C1q 反应者的肾移植功能在治疗后 3 年保持稳定。相比之下,C1q 无应答者的肾移植功能趋于恶化。活组织检查显示,75% 的 C1q 反应者评分有所改善,而 42.9% 的 C1q 无反应者评分恶化:结论:C1q-DSA 可以很好地预测 CABMR 治疗后的结果。
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