期刊
FRONTIERS IN IMMUNOLOGY
卷 13, 期 -, 页码 -出版社
FRONTIERS MEDIA SA
DOI: 10.3389/fimmu.2022.842354
关键词
multiple sclerosis; demyelinating diseases; ocrelizumab; B cells; biomarkers
类别
资金
- Red Espanola de Esclerosis Multiple (REEM) [RD16/0015/0001, RD16/0015/0002, RD16/0015/0003, RD16/0015/0008, RD16/0015/0013, PI18/00572]
- ISCIII-Subdireccion General de Evaluacion
- Fondo Europeo de Desarrollo Regional (FEDER, Una manera de hacer Europa)
This study aimed to investigate the role of inflammation in the response to ocrelizumab in patients with PPMS. The findings showed that over 60% of patients achieved no evidence of disease activity (NEDA) after one year of treatment, regardless of their baseline characteristics. The baseline inflammation influenced the predominant immunological pathways, with inflammatory B cells playing a pivotal role in Gd+ patients and inflammatory T and innate immune cells in Gd- patients.
Objective: To ascertain the role of inflammation in the response to ocrelizumab in primary-progressive multiple sclerosis (PPMS). Methods: Multicenter prospective study including 69 patients with PPMS who initiated ocrelizumab treatment, classified according to baseline presence [Gd+, n=16] or absence [Gd-, n=53] of gadolinium-enhancing lesions in brain MRI. Ten Gd+ (62.5%) and 41 Gd- patients (77.4%) showed non-evidence of disease activity (NEDA) defined as no disability progression or new MRI lesions after 1 year of treatment. Blood immune cell subsets were characterized by flow cytometry, serum immunoglobulins by nephelometry, and serum neurofilament light-chains (sNfL) by SIMOA. Statistical analyses were corrected with the Bonferroni formula. Results: More than 60% of patients reached NEDA after a year of treatment, regardless of their baseline characteristics. In Gd+ patients, it associated with a low repopulation rate of inflammatory B cells accompanied by a reduction of sNfL values 6 months after their first ocrelizumab dose. Patients in Gd- group also had low B cell numbers and sNfL values 6 months after initiating treatment, independent of their treatment response. In these patients, NEDA status was associated with a tolerogenic remodeling of the T and innate immune cell compartments, and with a clear increase of serum IgA levels. Conclusion: Baseline inflammation influences which immunological pathways predominate in patients with PPMS. Inflammatory B cells played a pivotal role in the Gd+ group and inflammatory T and innate immune cells in Gd- patients. B cell depletion can modulate both mechanisms.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据