Identification of novel autoantibodies to GABAB receptors in patients with neuropsychiatric systemic lupus erythematosus

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Objective. The gamma-aminobutyric acid type B receptors (GABARB) are G-protein coupled receptors for GABA, the main inhibitory neurotransmitter in the brain. We identified GABARB subunits as candidate antigens in patients with SLE using a random peptide display library. The aim of this study was to investigate the possible link between anti-GABARB antibodies and disease activity and NPSLE.

Methods. ELISA was performed with recombinant proteins of GABARB1b and GABARB2 on serum samples from patients with SLE (n = 88), scleroderma (n = 20), myositis (n = 20) or vasculitis (n = 20) as well as healthy subjects (n = 20). Cerebrospinal fluid (CSF) from 23 patients with SLE was also examined.

Results. Autoantibodies to GABARBs were exclusive to patients with SLE (P < 0.001) and positively associated with SLEDAI (anti-GABARB1b, P = 0.001; anti-GABARB2, P < 0.001). Of note, autoantibodies were positively linked with NPSLE (anti-GABARB1b, P = 0.02; anti-GABARB2, P = 0.03). Moreover, anti-GABARBs was detected in 61.5% of CSF samples from patients with active NPSLE, a frequency that was significantly higher than that for patients with non-SLE syndromes.

Conclusion. Anti-GABARB antibodies could represent novel candidate markers for disease activity and NPSLE.

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