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Anti-dsDNA IgE induces IL-4 production from basophils, potentially involved in B-cell differentiation in systemic lupus erythematosus.

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OBJECTS Recently, the involvement of basophils and IgE-type autoantibodies in the pathogenesis of systemic lupus erythematosus (SLE) has been elucidated using mouse models; however, few studies have been conducted in… Click to show full abstract

OBJECTS Recently, the involvement of basophils and IgE-type autoantibodies in the pathogenesis of systemic lupus erythematosus (SLE) has been elucidated using mouse models; however, few studies have been conducted in humans. In this study, the role of basophils and anti-double-stranded DNA (dsDNA) IgE in SLE was examined using human samples. METHODS The correlation between disease activity and serum levels of anti-dsDNA IgE in SLE was evaluated using enzyme-linked immunosorbent assay. Cytokines produced by IgE-stimulated basophils from healthy subjects were assessed using RNA sequences. The interaction of basophils and B cells to promote B cell differentiation was investigated using a co-culture system. The ability of basophils from patients with SLE with anti-dsDNA IgE to create cytokines which may be involved in B cell differentiation in response to dsDNA was examined using real-time polymerase chain reaction. RESULTS Anti-dsDNA IgE levels in the serum of patients with SLE correlated with disease activity. Healthy donor basophils produced IL-3, IL-4, and TGF-β1 after anti-IgE stimulation. Co-culture of B cells with anti-IgE-stimulated basophils increased plasmablasts which were cancelled by neutralizing IL-4. After encountering the antigen, basophils released IL-4 more quickly than follicular helper T cells. Basophils isolated from patients with anti-dsDNA IgE promoted IL-4 expression by adding dsDNA. CONCLUSIONS These results suggest that basophils contribute to the pathogenesis of SLE by promoting B cell differentiation via dsDNA-specific IgE in patients similar to the process described in mouse models.

Keywords: cell differentiation; dsdna ige; anti dsdna; dsdna

Journal Title: Rheumatology
Year Published: 2023

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