PDF(Pubmed)
Abstract：
UNASSIGNED: 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.
UNASSIGNED: 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.
UNASSIGNED: 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.
UNASSIGNED: Telitacicept lowered both circulating Gd-IgA1 and IgA-containing immune complexes, whereas IgA immune complex levels were more consistent with decreased proteinuria.
UNASSIGNED: 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.
UNASSIGNED: 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.
UNASSIGNED: Telitacicept lowered both circulating Gd-IgA1 and IgA-containing immune complexes, whereas IgA immune complex levels were more consistent with decreased proteinuria.
摘要：
■Telitacicept,跨膜激活剂和亲环素配体相互作用剂（TACI）融合蛋白靶向B细胞活化因子和增殖诱导配体（APRIL），已证明在治疗免疫球蛋白A（IgA）肾病（IgAN）中有效。然而,能够预测治疗期间临床反应的血清生物标志物尚不清楚.
■在基线和第4、12和24周后收集2期临床试验的24名参与者的血浆样本；安慰剂组中有8名参与者，在160mg组中有9个，240mg组中为7。我们测量了半乳糖缺陷型IgA1（Gd-IgA1）的水平，含IgA的免疫复合物，C3a,C5a,和sC5b-9。分析了这些标志物的变化与蛋白尿减少之间的关联。
■治疗24周后，Gd-IgA1下降了43.9%(95%置信区间：29.8%，55.1%），IgG-IgA免疫复合物占31.7%(14.4%，45.5%），和多聚IgA免疫复合物下降41.3%(6.5%，160mg组63.1%);Gd-IgA1下降50.4%(38.6%,59.9%），IgG-IgA免疫复合物下降42.7%(29.5%,53.4%），多聚IgA免疫复合物下降了67.2%(48.5%，240mg组的79.1%)。循环C3a没有显著变化，C5a,或telitacicept治疗期间的sC5b-9水平。血浆Gd-IgA1和IgG-IgA或poly-IgA免疫复合物的减少与蛋白尿减少有关。反过来,IgG-IgA或聚IgA免疫复合物显示出剂量依赖性效应，与telitacicept治疗期间蛋白尿减少一致。
■Telitacicept降低了循环的Gd-IgA1和含IgA的免疫复合物，而IgA免疫复合物水平与蛋白尿减少更一致。
■在基线和第4、12和24周后收集2期临床试验的24名参与者的血浆样本；安慰剂组中有8名参与者，在160mg组中有9个，240mg组中为7。我们测量了半乳糖缺陷型IgA1（Gd-IgA1）的水平，含IgA的免疫复合物，C3a,C5a,和sC5b-9。分析了这些标志物的变化与蛋白尿减少之间的关联。
■治疗24周后，Gd-IgA1下降了43.9%(95%置信区间：29.8%，55.1%），IgG-IgA免疫复合物占31.7%(14.4%，45.5%），和多聚IgA免疫复合物下降41.3%(6.5%，160mg组63.1%);Gd-IgA1下降50.4%(38.6%,59.9%），IgG-IgA免疫复合物下降42.7%(29.5%,53.4%），多聚IgA免疫复合物下降了67.2%(48.5%，240mg组的79.1%)。循环C3a没有显著变化，C5a,或telitacicept治疗期间的sC5b-9水平。血浆Gd-IgA1和IgG-IgA或poly-IgA免疫复合物的减少与蛋白尿减少有关。反过来,IgG-IgA或聚IgA免疫复合物显示出剂量依赖性效应，与telitacicept治疗期间蛋白尿减少一致。
■Telitacicept降低了循环的Gd-IgA1和含IgA的免疫复合物，而IgA免疫复合物水平与蛋白尿减少更一致。
