Department of Rheumatology and Immunology, Inselspital, Bern University Hospital, University of Bern, Bern, Switzerland.
Department of General Internal Medicine, Inselspital, Bern University Hospital, University of Bern, Bern, Switzerland.
Front Immunol. 2023 May 23;14:1165758. doi: 10.3389/fimmu.2023.1165758. eCollection 2023.
Proteome analyses in patients with newly diagnosed, untreated giant cell arteritis (GCA) have not been reported previously, nor are changes of protein expression upon treatment with glucocorticoids (GC) and/or tocilizumab (TCZ) known. The GUSTO trial allows to address these questions, provides the opportunity to learn about the differential effects of GC and TCZ on proteomics and may help to identify serum proteins to monitor disease activity.
Serum samples obtained from 16 patients with new-onset GCA at different time points (day 0, 3, 10, and week 4, 24, 52) during the GUSTO trial (NCT03745586) were examined for 1436 differentially expressed proteins (DEPs) based on proximity extension assay technology. The patients received 500 mg methylprednisolone intravenously for 3 consecutive days followed by TCZ monotherapy.
When comparing day 0 (before the first GC infusion) with week 52 (lasting remission), 434 DEPs (213↑, 221↓) were identified. In response to treatment, the majority of changes occurred within 10 days. GC inversely regulated 25 proteins compared to remission. No difference was observed between weeks 24 and 52 during established remission and ongoing TCZ treatment. Expression of CCL7, MMP12, and CXCL9 was not regulated by IL6.
Disease-regulated serum proteins improved within 10 days and were normalized within 24 weeks, showing a kinetic corresponding to the gradual achievement of clinical remission. The proteins inversely regulated by GC and TCZ shed light on the differential effects of the two drugs. CCL7, CXCL9, and MMP12 are biomarkers that reflect disease activity despite normalized C-reactive protein levels.
以前从未报道过新诊断、未经治疗的巨细胞动脉炎（GCA）患者的蛋白质组分析，也不知道糖皮质激素（GC）和/或托珠单抗（TCZ）治疗时蛋白质表达的变化。GUSTO 试验允许解决这些问题，提供了解 GC 和 TCZ 对蛋白质组学的差异影响的机会，并有助于确定监测疾病活动的血清蛋白。
根据邻近延伸分析技术，对 GUSTO 试验（NCT03745586）中不同时间点（第 0、3、10 天和第 4、24、52 周）的 16 例新发病 GCA 患者的血清样本进行了 1436 种差异表达蛋白（DEPs）的检测。患者接受 500mg 甲基强的松龙静脉滴注 3 天，然后单独使用 TCZ 治疗。
与第 52 周（持续缓解）相比，在第 0 天（第一次 GC 输注前）比较了 434 个 DEPs（213↑，221↓）。治疗后，大多数变化发生在 10 天内。GC 与缓解相比，反向调节了 25 个蛋白。在建立缓解和持续 TCZ 治疗期间，第 24 周和第 52 周之间没有差异。IL6 对 CCL7、MMP12 和 CXCL9 的表达没有调节作用。
疾病调节的血清蛋白在 10 天内得到改善，并在 24 周内恢复正常，表现出与逐渐达到临床缓解相对应的动力学。GC 和 TCZ 反向调节的蛋白阐明了两种药物的差异作用。CCL7、CXCL9 和 MMP12 是反映疾病活动的生物标志物，尽管 C 反应蛋白水平正常。
