S6D:4 Antibodies to myelin oligodendrocyte glycoprotein in patients with sle are associated with central nervous system involvement: an unbiased pilot study of the swiss sle cohort study (sscs)

Abstract

Background Nervous system involvement in systemic lupus erythematosus (SLE) is mediated either through autoimmune vascular or inflammatory processes. The aetiology leading to inflammatory processes to date remains largely elusive. Given that the pathophysiologic hallmark of SLE is B cell hyperreactivity, we hypothesised that antibodies against components of the central and peripheral nervous system might be present in the serum and contribute to inflammation/demyelination in these patients. Purpose To determine the prevalence of a broad panel of novel and known nervous system (NS)-directed antibodies in a large, unbiased cohort of patients with systemic lupus erythematosus (SLE) in the Swiss Lupus Erythematosus Cohort Study (SSCS). Methods This retrospective pilot study included 174 patients in a cross-sectional analysis and 104 patients in a longitudinal study. Antibodies against 12 NS-antigens (myelin oligodendrocyte glycoprotein (MOG), neurofascin 186 (NF186), aquaporin-4 (AQP4), N-methyl-d-aspartate receptor (NMDAR), AMPA-receptor subunit 1 and 2 (AMPAR), gamma-aminobutyric acid B receptor (GABABR), Glycin-receptor (GlyR), metabolic glutamate receptor 5 (mGluR5), glutamate decarboxylase 65 (GAD65), voltage-gated potassium channel (VGKC)-complex antibodies (contactin-associated protein-like 2 (CASPR2), Leucine-rich glioma inactivated 1 (LGI1)), and dipeptidyl-peptidase-like protein 6 (DPPX) were screened with cell-based assays and correlated with clinical and diagnostic findings. Results 23/174 patients harboured antibodies against MOG (n=14), NF186 (n=6), GAD65 (n=2), AQP4 and GlyR (n=1), of which 13 showed clinical symptoms of NS involvement that resembled the syndrome associated with the antibody. Nine patients harbouring antibodies have remained clinically asymptomatic to date, while another patient was lost to follow-up. Antibodies against MOG were those found most frequently (8%) and their titer correlated with the severity of neurologic involvement. The frequency of neuropsychiatric SLE (NPSLE) was much higher in the NS-antibody-positive patients (43%, 83%, 100%, 0% versus 14%). Conclusions Antibodies against MOG, NF186, GAD65, AQP4 and GlyR are found in patients with SLE and NS involvement, of which MOG-antibodies are the most prevalent. This is the first large, unbiased study to screen for a broad panel of anti-NS antibodies. Screening for these antibodies could serve as a predictor and biomarker for inflammatory NS involvement in NPSLE and potentially aid in tailored treatment decisions.