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B 细胞在自身免疫性疾病治疗后再群体化轨迹:一项纵向观察研究。

B cell repopulation trajectory after rituximab treatment in autoimmune diseases: a longitudinal observational study.

机构信息

Department of Rheumatology, National Clinical Research Center for Dermatologic and Immunologic Diseases, State Key Laboratory of Complex Severe and Rare Diseases, Key Laboratory of Rheumatology and Clinical Immunology, Ministry of Education, Peking Union Medical College Hospital, Chinese Academy of Medical Science and Peking Union Medical College, Beijing, China.

出版信息

Clin Exp Med. 2023 Dec;23(8):4787-4795. doi: 10.1007/s10238-023-01186-y. Epub 2023 Sep 26.

Abstract

To investigate B-cell repopulation trajectory and the associated factors in patients with autoimmune diseases (AIDs) who underwent rituximab (RTX) treatment. This is a retrospective study in a large tertiary medical center. Kaplan-Meier analysis and Cox regression were used to investigate factors associated with B-cell repopulation. Latent class trajectory modeling (LCTM) was employed to identify distinct B-cell repopulation trajectory longitudinally. A total of 224 patients were included, with a cumulative follow-up time of 193.6 person-years. Patients with antineutrophil cytoplasm antibody-associated vasculitis (AAV), connective tissue disease, and IgG4-related disease exhibited significant differences in B-cell repopulation time (p = 0.0055 by log-rank test). Multivariate Cox regression identified that higher levels of IgA (HR 1.21, 95%CI 1.01-1.45, p = 0.040) and concurrent glucocorticoid use (HR = 0.37,95%CI 0.20-0.67, p = 0.001) were associated with B-cell repopulation. The cluster showing prolonged B-cell depletion, identified by LCTM, had lower proportions of male (27% vs. 48.5%, p = 0.033), smoke history (17.6% vs. 38.7%, p = 0.025), higher proportions of AAV (44.3% vs. 15.2%, p = 0.004), RTX dose (p = 0.042), history of cyclophosphamide use (70.4% vs. 48.5%, p = 0.003), meanwhile glucocorticoid use (94.8% vs. 72.7%, p = 0.001). The trajectory of B-cell repopulation after RTX infusion in AIDs was heterogeneous. Certain factors were associated with B-cell repopulation, and a specific cluster of patients demonstrated prolonged B-cell depletion after RTX treatment.

摘要

研究接受利妥昔单抗(RTX)治疗的自身免疫性疾病(AIDs)患者 B 细胞再增殖轨迹及其相关因素。这是一项在大型三级医疗中心进行的回顾性研究。采用 Kaplan-Meier 分析和 Cox 回归分析探讨与 B 细胞再增殖相关的因素。采用潜在类别轨迹建模(LCTM)从纵向角度确定不同的 B 细胞再增殖轨迹。共纳入 224 例患者,累积随访时间为 193.6 人年。抗中性粒细胞胞质抗体相关性血管炎(AAV)、结缔组织病和 IgG4 相关疾病患者的 B 细胞再增殖时间存在显著差异(log-rank 检验,p=0.0055)。多变量 Cox 回归分析确定,较高的 IgA 水平(HR 1.21,95%CI 1.01-1.45,p=0.040)和同时使用糖皮质激素(HR=0.37,95%CI 0.20-0.67,p=0.001)与 B 细胞再增殖相关。通过 LCTM 确定的 B 细胞耗竭时间延长的聚类,男性比例较低(27%比 48.5%,p=0.033),吸烟史比例较低(17.6%比 38.7%,p=0.025),AAV 比例较高(44.3%比 15.2%,p=0.004),RTX 剂量较高(p=0.042),环磷酰胺使用史比例较高(70.4%比 48.5%,p=0.003),同时糖皮质激素使用率较高(94.8%比 72.7%,p=0.001)。RTX 输注后 AIDs 患者 B 细胞再增殖轨迹存在异质性。某些因素与 B 细胞再增殖相关,并且特定的患者聚类在接受 RTX 治疗后表现出 B 细胞耗竭延长。

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