Dataset Information

Diminished LAG3⁺ B cells correlate with exacerbated rheumatoid arthritis.

ABSTRACT:

Background

Lymphocyte activation gene-3 (LAG3) positive B cells have been identified as a novel regulatory B cell subset, while the role of LAG3⁺ B cells in the pathogenesis of rheumatoid arthritis (RA) remains elusive.

Materials and methods

Peripheral blood mononuclear cells (PBMCs) from RA, osteoarthritis (OA) patients and healthy volunteers were collected for flow cytometry staining of LAG3⁺ B cells. Their correlation with RA patient clinical and immunological features were analyzed. Moreover, the frequencies of LAG3⁺ B cells in collagen-induced arthritis (CIA) mice and naive mice were also detected.

Results

A significant decrease of LAG3⁺ B cells was observed in RA patients as compared with healthy individuals and OA patients. Notably, the frequencies of LAG3⁺ B cells were negatively correlated with tender joint count (r = -0.4301, p = .0157) and DAS28-ESR (r = -0.4018, p = .025) in RA patients. In CIA mice, LAG3⁺ B cell frequencies were also decreased and negatively correlated with the CIA arthritis score.

Conclusions

Impairment of LAG3⁺ B cells potentially contributes to RA development. Reconstituting LAG3⁺ B cells might provide novel therapeutic strategies for the persistent disease.Key messagesLAG3⁺ B cells have been identified as a novel regulatory B cell subset. However, its role in the pathogenesis of RA remains unknown.This study revealed the decreased frequency of LAG3⁺ B cells in RA patients. Notably, LAG3⁺ B cells were negatively correlated with RA disease activity including the tender joint count and DAS28-ESR.In CIA mice, LAG3⁺ B cell frequencies were also decreased and negatively correlated with the CIA arthritis score.Reconstitution of LAG3⁺ B cells might provide novel therapeutic strategies for disease perpetuation.

SUBMITTER: Hu S

PROVIDER: S-EPMC10165927 | biostudies-literature | 2023 Dec

REPOSITORIES: biostudies-literature

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Publications

Diminished LAG3<sup>+</sup> B cells correlate with exacerbated rheumatoid arthritis.

Hu Suiyuan S Tao Yuting Y Hu Fanlei F Liu Xu X

Annals of medicine 20231201 1

<h4>Background</h4>Lymphocyte activation gene-3 (LAG3) positive B cells have been identified as a novel regulatory B cell subset, while the role of LAG3<sup>+</sup> B cells in the pathogenesis of rheumatoid arthritis (RA) remains elusive.<h4>Materials and methods</h4>Peripheral blood mononuclear cells (PBMCs) from RA, osteoarthritis (OA) patients and healthy volunteers were collected for flow cytometry staining of LAG3<sup>+</sup> B cells. Their correlation with RA patient clinical and immunolog ...[more]

PMID: 37143367

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Project description:IntroductionRheumatoid arthritis (RA) is a complex and clinically heterogeneous autoimmune disease. Currently, the relationship between pathogenic molecular drivers of disease in RA and therapeutic response is poorly understood.MethodsWe analyzed synovial tissue samples from two RA cohorts of 49 and 20 patients using a combination of global gene expression, histologic and cellular analyses, and analysis of gene expression data from two further publicly available RA cohorts. To identify candidate serum biomarkers that correspond to differential synovial biology and clinical response to targeted therapies, we performed pre-treatment biomarker analysis compared with therapeutic outcome at week 24 in serum samples from 198 patients from the ADACTA (ADalimumab ACTemrA) phase 4 trial of tocilizumab (anti-IL-6R) monotherapy versus adalimumab (anti-TNFα) monotherapy.ResultsWe documented evidence for four major phenotypes of RA synovium - lymphoid, myeloid, low inflammatory, and fibroid - each with distinct underlying gene expression signatures. We observed that baseline synovial myeloid, but not lymphoid, gene signature expression was higher in patients with good compared with poor European league against rheumatism (EULAR) clinical response to anti-TNFα therapy at week 16 (P =0.011). We observed that high baseline serum soluble intercellular adhesion molecule 1 (sICAM1), associated with the myeloid phenotype, and high serum C-X-C motif chemokine 13 (CXCL13), associated with the lymphoid phenotype, had differential relationships with clinical response to anti-TNFα compared with anti-IL6R treatment. sICAM1-high/CXCL13-low patients showed the highest week 24 American College of Rheumatology (ACR) 50 response rate to anti-TNFα treatment as compared with sICAM1-low/CXCL13-high patients (42% versus 13%, respectively, P =0.05) while anti-IL-6R patients showed the opposite relationship with these biomarker subgroups (ACR50 20% versus 69%, P =0.004).ConclusionsThese data demonstrate that underlying molecular and cellular heterogeneity in RA impacts clinical outcome to therapies targeting different biological pathways, with patients with the myeloid phenotype exhibiting the most robust response to anti-TNFα. These data suggest a path to identify and validate serum biomarkers that predict response to targeted therapies in rheumatoid arthritis and possibly other autoimmune diseases.Trial registrationClinicalTrials.gov NCT01119859

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Dataset Information

Diminished LAG3⁺ B cells correlate with exacerbated rheumatoid arthritis.

Background

Materials and methods

Results

Conclusions

Publications

Diminished LAG3<sup>+</sup> B cells correlate with exacerbated rheumatoid arthritis.

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Dataset Information

Diminished LAG3+ B cells correlate with exacerbated rheumatoid arthritis.

Background

Materials and methods

Results

Conclusions

Publications

Diminished LAG3<sup>+</sup> B cells correlate with exacerbated rheumatoid arthritis.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets

Diminished LAG3⁺ B cells correlate with exacerbated rheumatoid arthritis.