Inflammatory Diseases Of The Central And Peripheral Nervous System In Patients With Systemic Lupus Erythematosus: Autoantibody Findings And Clinical Phenotype

Background:Systemic lupus erythematosus (SLE) is an autoimmune connective tissue disease affecting various organs including the nervous system. It is characterized by cytokine dysregulation, polyclonal B cell activation, autoantibody production, and increased immune complex formation. Cerebral involvement most frequently results from microvasculopathy. Some patients present with demyelinating lesions or encephalitis. Previous studies have pointed towards autoimmune overlap syndromes between SLE and neuromyelitis optica or encephalitis. However, the target antigens often still remain elusive.Aim:To assess the frequency of established and novel antibodies targeting CNS/PNS antigens and to correlate antibody findings to clinical, laboratory, and MRI data in a large, blinded cohort of SLE patients.Methods:Using cell-based assays, we analyzed the presence of antibodies against myelin oligodendrocyte glycoprotein (MOG), aquaporin-4 (AQP4), neurofascin 186 (NF186), NMDA-receptor, AMPA-receptor 1/2, GABAB-receptor, Glycin-receptor (GlyR), metabolic glutamate receptor 5 (mGluR5), Leucine-rich glioma inactivated 1 (LGI1), contactin-associated protein-like 2 (CASPR2), dipeptidyl-peptidase-like protein 6 (DPPX) as well as glutamic acid decarboxylase (GAD65) in 174 patients from the Swiss Lupus Cohort at baseline and follow-ups.Results:Of 174 SLE patients, anti-MOG-antibodies were identified in 15 patients (8.6[percnt]), anti-NF-antibodies in 5 patients (2.9[percnt]), and low-titer anti-GAD65-antibodies in 2 patients. One patient harbored anti-AQP4- and anti-GlyR-antibodies. Data on the correlation of autoantibody findings with clinical manifestations and MRI results will be presented.Conclusion:Antibodies associated with demyelinating CNS/PNS diseases (anti-MOG/-NF/-AQP4) are present in a subgroup of SLE patients. Ongoing analysis needs to clarify whether these autoantibodies are merely part of an unspecific, polyclonal B cell activity, or correlate with a demyelinating phenotype, which seems to be the case at least in some. The identification of these autoantibodies in SLE patients with features of demyelinating CNS/PNS disease might serve as a biomarker to differentiate them from vasculitic damage and lead to a more targeted therapy such as B cell depletion. Disclosure: Dr. Proebstel has received personal compensation for activities with Genzyme Corporation and Baxalta. Dr. Thanai has nothing to disclose. Dr. Erni has nothing to disclose. Dr. Anne-Catherine has nothing to disclose. Dr. Branco has nothing to disclose. Dr. Ribi has nothing to disclose. Dr. Koenig has nothing to disclose. Dr. Huynh-Do has nothing to disclose. Dr. Chizzolini has received personal compensation for activities with Roche, Baxter Int., and Actelion. Dr. Kappos9s institution (University Hospital Basel) has received royalty payments from Neurostatus Systems GmbH. Dr. Trendelenburg has nothing to disclose. Dr. Derfuss has received research support from Biogen Idec and Novartis Pharma.