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Determining Immune System Suppression versus CNS Protection for Pharmacological Interventions in Autoimmune Demyelination

Determining Immune System Suppression versus CNS Protection for Pharmacological Interventions in Autoimmune Demyelination

Published on: September 12, 2016

B cell depletion therapy does not resolve chronic active multiple sclerosis lesions.

Pietro Maggi¹, Colin Vanden Bulcke², Edoardo Pedrini³

¹Cliniques Universitaires Saint-Luc, Université Catholique de Louvain, Brussels, Belgium; Neuroinflammation Imaging Lab (NIL), Université Catholique de Louvain, Brussels, Belgium; Centre Hospitalier Universitaire Vaudois, Université de Lausanne, Lausanne, Switzerland.

|July 12, 2023

Summary

Anti-CD20 therapies show limited effect on chronic active lesions in multiple sclerosis (MS). These treatments did not resolve paramagnetic rims (PRL) and did not prevent progression independent of relapse activity (PIRA).

Keywords:

Anti-CD20 treatment Machine learning Paramagnetic rims Single cell RNA sequencing Susceptibility-based MRI

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Flow Cytometric Analysis of Lymphocyte Infiltration in Central Nervous System during Experimental Autoimmune Encephalomyelitis

Flow Cytometric Analysis of Lymphocyte Infiltration in Central Nervous System during Experimental Autoimmune Encephalomyelitis

Published on: November 17, 2020

Area of Science:

Neuroimmunology
Multiple Sclerosis Pathogenesis
Therapeutic Development

Background:

Chronic active lesions (CAL) in multiple sclerosis (MS) contribute to disease progression, including progression independent of relapse activity (PIRA).
Understanding the impact of targeting specific lymphocyte populations is crucial for developing advanced MS therapies to manage chronic inflammation.

Purpose of the Study:

To bioinformatically predict the effects of lymphocyte depletion in CAL.
To assess the in vivo MRI changes in paramagnetic rims (PRL) in MS patients treated with anti-CD20 antibodies compared to untreated patients.

Main Methods:

Analysis of published lymphocyte single-cell transcriptomes from MS lesions.
Gene-regulatory-network machine-learning to predict effects of lymphocyte subpopulation depletion.
In vivo MRI assessment of PRL changes over approximately 2 years in treated and untreated MS patients.

Main Results:

CD20 B-cells constituted only 4.3% of lymphocytes in CAL, but their depletion was predicted to impact microglial genes related to iron metabolism, hypoxia, and antigen presentation.
No disappearance of treated PRL was observed over follow-up; no treatment effect on PRL volume, magnetic susceptibility, or T1 time.
Progression independent of relapse activity (PIRA) occurred in 20% of treated patients, more frequently in those with four or more PRL.

Conclusions:

Anti-CD20 therapies did not fully resolve paramagnetic rims (PRL) after 2-year MRI follow-up, despite predicted effects on microglia-mediated inflammatory networks.
Potential reasons for limited efficacy include low B-cell turnover in MS lesions, inefficient blood-brain barrier penetration of anti-CD20 antibodies, and a scarcity of B-cells within CAL.