AI Article Synopsis
- The study aimed to understand how inflammation affects the response to ocrelizumab treatment in patients with primary-progressive multiple sclerosis (PPMS).
- Researchers followed 69 patients, looking at those with and without gadolinium-enhancing lesions on MRI, finding that over 60% achieved "no evidence of disease activity" (NEDA) after one year.
- The results suggested that in patients with Gd+ lesions, a low rate of inflammatory B cells and decreased serum neurofilament levels were significant, while in Gd- patients, NEDA was associated with changes in other immune cells and increased serum IgA levels.
Article Abstract
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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| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8977599 | PMC |
| http://dx.doi.org/10.3389/fimmu.2022.842354 | DOI Listing |
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