Journal
FRONTIERS IN IMMUNOLOGY
Volume 13, Issue -, Pages -Publisher
FRONTIERS MEDIA SA
DOI: 10.3389/fimmu.2022.842354
Keywords
multiple sclerosis; demyelinating diseases; ocrelizumab; B cells; biomarkers
Categories
Funding
- 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)
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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.
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