ObjectivesAge-associated B cells (ABCs) are a recently identified B cell subset, whose expansion has been increasingly linked to the pathogenesis of autoimmune disorders. This study aimed to investigate whether ABCs are involved in the pathogenesis and underlying mechanisms of rheumatoid arthritis (RA).MethodsABCs were assessed in collagen-induced arthritis (CIA) mice and patients with RA using flow cytometry. Transcriptomic features of RA ABCs were explored using RNA-seq. Primary fibroblast-like synoviocytes (FLS) derived from the synovial tissue of patients with RA were cocultured with ABCs or ABCs-conditioned medium (ABCsCM). IL-6, MMP-1, MMP-3 and MMP-13 levels in the coculture supernatant were detected by ELISA. Signalling pathways related to ABCs-induced FLS activation were examined using western blotting.ResultsIncreased ABCs levels in the blood, spleen and inflammatory joints of CIA mice were observed. Notably, ABCs were elevated in the blood, synovial fluid and synovial tissue of patients with RA and positively correlated with disease activity. RNA-seq revealed upregulated chemotaxis-related genes in RA ABCs compared with those in naive and memory B cells. Coculture of FLS with RA ABCs or ABCsCM led to an active phenotype of FLS, with increased production of IL-6, MMP-1, MMP-3 and MMP-13. Mechanistically, ABCsCM-derived TNF-α promoted the upregulation of interferon-stimulated genes in FLS, with elevated phosphorylation of ERK1/2 and STAT1. Furthermore, blockage of ERK1/2 and Janus Kinase (JAK)-STAT1 pathways inhibited the activation of FLS induced by ABCsCM.ConclusionsOur results suggest that ABCs contribute to the pathogenesis of RA by inducing the activation of FLS via TNF-α-mediated ERK1/2 and JAK-STAT1 pathways.
Eosinophils are a minor component of circulating granulocytes, which are classically viewed as end-stage effector cells in host defense against helminth infection and promoting allergic responses. However, a growing body of evidence has emerged showing that eosinophils are versatile leukocytes acting as an orchestrator in the resolution of inflammation. Rheumatoid arthritis (RA) is the most common chronic inflammatory disease characterized by persistent synovitis that hardly resolves spontaneously. Noteworthy, a specific population of eosinophils, that is, regulatory eosinophils (rEos), was identified in the synovium of RA patients, especially in disease remission. Mechanistically, the rEos in the synovium display a unique pro-resolving signature that is distinct from their counterpart in the lung. Herein, we summarize the latest understanding of eosinophils and their emerging role in promoting the resolution of arthritis. This knowledge is crucial to the design of new approaches to rebalancing immune homeostasis in RA, considering that current therapies are centered on inhibiting pro-inflammatory cytokines and mediators rather than fostering the resolution of inflammation.
Objectives The surge of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variant Omicron infections has affected most Chinese residents at the end of 2022, including a number of patients with systemic autoimmune rheumatic diseases (SARDs). Methods To investigate the antibody level of the Omicron variant in SARDs patients after SARS-CoV-2 Omicron infection, we tested BA.5.2 and BF.7 Omicron variant IgG antibody level using enzyme-linked immunosorbent assay (ELISA) from the collected blood samples from 102 SARDs patients and 19 healthy controls (HCs). The type of SARDs, demographics, concurrent treatment, doses of SARS-CoV-2 vaccines, and outcomes were also recorded. Results A total of 102 SARDs patients (mean age, 40.3 years, 89.2% female), including 60 systemic lupus erythematosus (SLE), 32 rheumatoid arthritis (RA) and 10 other SARDs, were identified. Of these, 87 (85.3%) were infected with SARS-CoV-2. We found that the BA.5.2 and BF.7 antibody levels of infected SARDs patients were lower than those of HCs (p < 0.05). 65(63.7%) patients had at least one dose of a SARS-CoV-2 vaccine. SARDs patients with at least two doses SARS-CoV-2 vaccine had a higher level of BA.5.2 and BF.7 antibody than unvaccinated group (p < 0.05). There was no evidence for significant inhibition effect of glucocorticoids (GCs) on the BA.5.2 and BF.7 Omicron variant antibody level in SARDs patients. SLE patients with bDMARDs use had a lower BA.5.2 Omicron variant antibody level than patients with GCs and/or hydroxychloroquine use. Conclusion These data suggest that patients with SARDs had a lower antibody response than healthy controls after Omicron infection. Lay summary What does this mean for patients ? SARS-CoV-2 is a type of coronavirus that causes COVID-19. Spread of SARS-CoV-2 lead to the COVID-19 pandemic and a global threat to public health. Different variants of SARS-CoV-2 have developed as the virus changes over time. Omicron is one such variant. Patients with systemic autoimmune rheumatic diseases (SARDs), such as rheumatoid arthritis, systemic lupus erythematosus and Sjögren’s syndrome, are often treated with drugs called immunosuppressants. Immunosuppressants make your immune system less active, meaning that it is harder to defend against diseases like COVID-19. As a result, SARD patients are at higher risk of developing severe COVID-19. We performed a study to describe the characteristics and immune responses of SARD patients with COVID-19 Omicron infection in China. We found that SARD patients had fewer antibodies against Omicron than healthy people. We also found that lupus patients who used biologic drugs had a lower antibody level than those using glucocorticoids (steroids) and/or hydroxychloroquine. Importantly, SARD patients who had at least two doses of SARS-CoV-2 vaccine had higher levels of antibodies than unvaccinated patients. These findings suggest that patients with SARDs have a lower antibody response after Omicron infection than healthy people, meaning that their immune systems are less able to defend against future re-infection. Our data therefore support the importance of COVID-19 booster vaccination among patients with SARDs.
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