Фенотипические изменения в клетке Моноцита с высоким интерлейкин-1 Бета экспресс во время долгосрочной анти-CD20 терапии.
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Waede Mie, Kingo Christina, Damsbo Karina, Joergensen Maiken Uhrbrand, Oubounyt Mhaned, Gjerstorff Morten, Thomassen Mads, Baumbach Jan, Moeller Jesper B, Elkjaer Maria L, Illes Zsolt
Аннотация
Оригинал публикации
Phenotypic Changes in a Monocyte Cluster with High Interleukin-1 Beta Expression during Long-Term Anti-CD20 Therapy.
OBJECTIVE: We aimed to investigate disease-related and anti-CD20 therapy-related changes in peripheral blood mononuclear cells (PBMCs) from multiple sclerosis (MS) patients compared to healthy controls (HC) using multi-omics single-cell analysis.
METHODS: Targeted single-cell sequencing of transcriptomes and epitopes was performed on PBMCs isolated from 64 blood samples collected from MS patients at baseline and at 3 time points following anti-CD20 treatment, alongside HC. Multicolor spectral flow cytometry was performed on 15 of the samples.
RESULTS: Cell cluster analysis identified a subpopulation of classical monocytes with significantly high interleukin-1 beta (IL1B) expression and a pro-inflammatory profile compared to other monocyte clusters. This monocyte cluster expressed genes of pro-inflammatory chemokines and cytokines, such as CXCL8, CCL3, CCL4, and TNFα and was a major cell transmitter subset within the intercellular communication network. The IL1Bhigh monocyte cluster was prevalent in HC (8.1% of PBMCs), but reduced in untreated MS patients (0.8% of PBMCs). High CXCR4 expression and Gene Ontology-term analysis indicated that IL1Bhigh monocytes from MS patients had central nervous system (CNS)-infiltrating abilities in contrast to HC, likely regulated by LEF1. After anti-CD20 treatment, IL1Bhigh monocytes showed changes in pro-inflammatory gene expression and MYC-associated regulatory networks, and their abundance increased 6-fold in the blood.
INTERPRETATION: Our single-cell analysis identified a unique peripheral IL1Bhigh monocyte cluster with a suggested CNS-infiltrating cellular phenotype that may explain its lower abundance in the blood of untreated compared to anti-CD20 treated MS patients. Treatment-associated changes in this population may contribute to the non-B cell related effects of anti-CD20 therapy. ANN NEUROL 2025;98:1283-1298.