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Related Concept Videos

T Cell Types and Functions01:24

T Cell Types and Functions

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When T cells with CD4 markers are activated, they give rise to two types of effector cells: helper T cells and regulatory T cells. Meanwhile, T cells with CD8 markers differentiate into effector cytotoxic T cells. The differentiation of CD4 T cells into helper T cell subsets, such as Th1, Th2, and Th17 cells, is dependent on the antigen type, antigen-presenting cell, and regulatory cytokines.
Th1 cells stimulate dendritic cells to express necessary co-stimulatory molecules on their surfaces for...
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Determining Immune System Suppression versus CNS Protection for Pharmacological Interventions in Autoimmune Demyelination
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Baseline Inflammatory Status Reveals Dichotomic Immune Mechanisms Involved In Primary-Progressive Multiple Sclerosis

José I Fernández-Velasco1, Enric Monreal2, Jens Kuhle3

  • 1Immunology Department, Ramon y Cajal University Hospital, Madrid, Spain.

Frontiers in Immunology
|April 7, 2022
PubMed
Summary

Inflammation influences ocrelizumab response in primary-progressive multiple sclerosis (PPMS). Baseline inflammation type dictates immune cell activity, but B cell depletion may modulate these pathways for treatment effectiveness.

Keywords:
B cellsbiomarkersdemyelinating diseasesmultiple sclerosisocrelizumab

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Area of Science:

  • Neuroimmunology
  • Inflammation and Autoimmunity
  • Therapeutic Response Biomarkers

Background:

  • Primary-progressive multiple sclerosis (PPMS) is a debilitating neurodegenerative disease.
  • Ocrelizumab is a B-cell depleting therapy approved for PPMS.
  • Understanding treatment response mechanisms is crucial for optimizing patient outcomes.

Purpose of the Study:

  • To investigate the role of baseline inflammation in predicting response to ocrelizumab in PPMS patients.
  • To identify immunological markers associated with treatment response and disease activity.

Main Methods:

  • Prospective multicenter study of 69 PPMS patients initiating ocrelizumab.
  • Classification based on baseline MRI gadolinium-enhancing lesions (Gd+ vs. Gd-).
  • Assessment of immune cell subsets, serum immunoglobulins, and neurofilament light-chains (sNfL).

Main Results:

  • Over 60% of patients achieved non-evidence of disease activity (NEDA) after one year.
  • Gd+ patients with NEDA showed reduced B-cell repopulation and decreased sNfL.
  • Gd- patients with NEDA exhibited tolerogenic immune remodeling and increased IgA.

Conclusions:

  • Baseline inflammation dictates distinct immunological pathways in PPMS patients treated with ocrelizumab.
  • Inflammatory B cells are key in Gd+ patients, while T and innate cells are crucial in Gd- patients.
  • B-cell depletion offers a potential mechanism to modulate these diverse inflammatory pathways.