Tu142 - Investigating Autoantibody Specificities in Lupus Target Organs: A Correlation with Inflammatory Biomarkers

Abstract Text: Systemic lupus erythematosus (SLE) is characterized by dysregulated immune responses, often leading to organ damage. B cells play a key role in lupus pathogenesis, as evidenced by the success of B cell targeting therapies. While serum autoantibody profiles are well-studied and can serve as biomarkers of lupus, less is known about B cell reactivity in target organs. To address this gap, we analyzed autoantibody profiles in cerebrospinal fluid (CSF) of neuropsychiatric lupus (NPSLE) patients and interstitial skin fluid of cutaneous lupus erythematosus (CLE) patients using a human immunoglobulin isotyping panel. Our findings indicate that the CSF of NPSLE patients contains IgG1, IgG3, and IgA. We also compared the blister fluid of CLE patients and healthy patients, and found that CLE patients demonstrate higher levels of IgM in their blister fluid, but lower levels of IgG3, IgG4, and IgA as compared to healthy controls. Finally, we analyzed the cytokine expression in these fluids to identify potential factors for B cell isotype class switching. NPSLE patients had higher levels of CXCL10 and IL-8 and lower levels of IL-1β and IFN-β as compared to other neuroinflammatory conditions. CLE patients had higher levels of multiple cytokines and chemokines, most notably IFN and IFN-inducible chemokines including CXCL10. We plan to analyze which autoantigens are recognized by IgM in the skin and IgG1/3 and IgA in the CSF. This study provides novel insights into organ-specific B cell reactivity in lupus, with implications for targeted therapeutic strategies.