Zan Jincan, Liu Lijun, Li Guisen, Zheng Hongguang, Chen Nan, Wang Caili, Xie Deqiong, Zuo Li, Li Rongshan, Zhang Pengfei, Wang Yue, Wang Wenxiang, Li Lin, Fang Jianmin, Lv Jicheng, Zhang Hong
Renal Division, Peking University First Hospital Peking University Institute of Nephrology Key Laboratory of Renal Disease, Ministry of Health of China Key Laboratory of Chronic Kidney Disease Prevention and Treatment (Peking University), Ministry of Education. Research Units of Diagnosis and Treatment of Immune-mediate Kidney Disease, Chinese Academy of Medical Sciences, Beijing, China.
Renal Division and Institute of Nephrology, Sichuan Provincial People's Hospital, School of Medicine, University of Electronic Science and Technology of China, Sichuan, China.
Kidney Int Rep. 2024 Jan 10;9(4):1067-1071. doi: 10.1016/j.ekir.2024.01.003. eCollection 2024 Apr.
Telitacicept, a transmembrane activator and cyclophilin ligand interactor (TACI) fusion protein targeting B cell activating factor and a proliferation-inducing ligand (APRIL), has proven efficacy in treating Immunoglobulin A (IgA) nephropathy (IgAN). However, serum biomarkers that could predict the clinical response during the treatment remain unclear.
Plasma samples from 24 participants in the phase 2 clinical trial were collected at baseline and after 4, 12, and 24 weeks; with 8 participants in the placebo group, 9 in the 160 mg group, and 7 in the 240 mg group. We measured the levels of galactose-deficient-IgA1 (Gd-IgA1), IgA-containing immune complexes, C3a, C5a, and sC5b-9. The association between the changes in these markers and proteinuria reduction was analyzed.
After 24 weeks of treatment, Gd-IgA1 decreased by 43.9% (95% confidence interval: 29.8%, 55.1%), IgG-IgA immune complex by 31.7% (14.4%, 45.5%), and poly-IgA immune complex by 41.3% (6.5%, 63.1%) in the 160 mg group; Gd-IgA1 decreased by 50.4% (38.6%, 59.9%), IgG-IgA immune complex decreased by 42.7% (29.5%, 53.4%), and poly-IgA immune complex decreased by 67.2% (48.5%,79.1%) in the 240 mg group. There were no significant changes in the circulatory C3a, C5a, or sC5b-9 levels during telitacicept treatment. Decreases in both plasma Gd-IgA1 and IgG-IgA or poly-IgA immune complexes were associated with proteinuria reduction. In turn, IgG-IgA or poly-IgA immune complexes showed a dose-dependent effect, consistent with proteinuria reduction during telitacicept treatment.
Telitacicept lowered both circulating Gd-IgA1 and IgA-containing immune complexes, whereas IgA immune complex levels were more consistent with decreased proteinuria.
泰利妥昔单抗是一种靶向B细胞活化因子和增殖诱导配体（APRIL）的跨膜激活剂与亲环素配体相互作用分子（TACI）融合蛋白，已被证明在治疗免疫球蛋白A（IgA）肾病（IgAN）方面具有疗效。然而，能够预测治疗期间临床反应的血清生物标志物仍不明确。
收集了24名参与2期临床试验的受试者在基线以及第4、12和24周后的血浆样本；其中安慰剂组8名受试者，160mg组9名受试者，240mg组7名受试者。我们检测了半乳糖缺陷型IgA1（Gd-IgA1）、含IgA免疫复合物、C3a、C5a和sC5b-9的水平。分析了这些标志物变化与蛋白尿减少之间的关联。
治疗24周后，160mg组中Gd-IgA1下降了43.9%（95%置信区间：29.8%，55.1%），IgG-IgA免疫复合物下降了31.7%（14.4%，45.5%），多聚IgA免疫复合物下降了41.3%（6.5%，63.1%）；240mg组中Gd-IgA1下降了50.4%（38.6%，59.9%），IgG-IgA免疫复合物下降了42.7%（29.5%，53.4%），多聚IgA免疫复合物下降了67.2%（48.5%，79.1%）。在泰利妥昔单抗治疗期间，循环中的C3a、C5a或sC5b-9水平无显著变化。血浆Gd-IgA1以及IgG-IgA或多聚IgA免疫复合物的降低均与蛋白尿减少相关。反过来，IgG-IgA或多聚IgA免疫复合物呈现出剂量依赖性效应，这与泰利妥昔单抗治疗期间蛋白尿减少情况一致。
泰利妥昔单抗降低了循环中的Gd-IgA1和含IgA免疫复合物水平，而IgA免疫复合物水平与蛋白尿减少更为一致。
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