Phenotypic Changes in a Monocyte Cluster with High Interleukin-1 Beta Expression during Long-Term Anti-CD20 Therapy

Area of Science:

• Immunology
• Neuroscience
• Genomics

Background:

• Multiple sclerosis (MS) is a chronic inflammatory disease of the central nervous system (CNS).
• Peripheral blood mononuclear cells (PBMCs) play a role in MS pathogenesis.
• Anti-CD20 therapies target B cells but may have non-B cell effects.

Purpose of the Study:

• To investigate disease- and anti-CD20 therapy-related changes in PBMCs from MS patients versus healthy controls (HC).
• To utilize multi-omics single-cell analysis for detailed cellular profiling.

Main Methods:

• Targeted single-cell sequencing of transcriptomes and epitopes on PBMCs from 64 MS patients and HC.
• Analysis of samples at baseline and multiple time points post-anti-CD20 treatment.
• Multicolor spectral flow cytometry on a subset of samples.

Main Results:

• A pro-inflammatory monocyte subpopulation with high IL1B expression (IL1Bhigh) was identified.
• IL1Bhigh monocytes were reduced in untreated MS patients compared to HC.
• These monocytes exhibited CNS-infiltrating potential and increased significantly after anti-CD20 therapy.

Conclusions:

• A distinct peripheral IL1Bhigh monocyte cluster with CNS-infiltrating potential was found.
• Reduced abundance in untreated MS patients may be linked to CNS infiltration.
• Treatment-induced changes in IL1Bhigh monocytes could explain non-B cell effects of anti-CD20 therapy.