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Background and Objectives: antibodies to CD20 efficiently reduce new relapses in multiple sclerosis (MS), and ocrelizumab has been shown to be effective also in primary progressive MS. Although anti-CD20 treatments efficiently deplete B cells in blood, some B cells and CD20(-) plasma cells persist in lymphatic organs and the inflamed CNS; their survival is regulated by the B cell-activating factor (BAFF)/A proliferation-inducing ligand (APRIL) system. The administration of a soluble receptor for BAFF and APRIL, atacicept, unexpectedly worsened MS. Here, we explored the long-term effects of ocrelizumab on immune cell subsets as well as on cytokines and endogenous soluble receptors comprising the BAFF-APRIL system.Methods: we analyzed immune cell subsets and B cell-regulating factors longitudinally for up to 2.5 years in patients with MS treated with ocrelizumab. In a second cohort, we determined B-cell regulatory factors in the CSF before and after ocrelizumab. We quantified the cytokines BAFF and APRIL along with their endogenous soluble receptors soluble B-cell maturation antigen (sBCMA) and soluble transmembrane activator and calcium-modulator and cyclophilin ligand (CAML) interactor (sTACI) using enzyme-linked immunosorbent assays (ELISAs). In addition, we established an in-house ELISA to measure sTACI-BAFF complexes.Results: ocrelizumab treatment of people with MS persistently depleted B cells and CD20(+) T cells. This treatment enhanced BAFF and reduced the free endogenous soluble receptor and decoy sTACI in both serum and CSF. Levels of sTACI negatively correlated with BAFF levels. Reduction of sTACI was associated with formation of sTACI-BAFF complexes.Discussion: we describe a novel effect of anti-CD20 therapy on the BAFF-APRIL system, namely reduction of sTACI. Because sTACI is a decoy for APRIL, its reduction may enhance local APRIL activity, thereby promoting regulatory IgA(+) plasma cells and astrocytic interleukin (IL)-10 production. Thus, reducing sTAC, This work was supported by the DFG (SFB TR128) to E.M., the Verein zur Therapieforschung f¨ur MS Kranke to E.M., by Roche to E.M. and the Else Kr¨oner-Fresenius-Stiftung (EKFS) to S.M.

Neuropsychiatric systemic lupus erythematosus is an autoimmune disorder characterized by an irregular exchange between the central nervous system and the immune system, leading to the outbreak of neurological conditions with possible disabling effects. Although neuropsychiatric systemic lupus erythematosus is the most common expression of lupus condition, it is still poorly understood. In this study, we focus on the development of an advantageous method based on the application of synthetic nucleic acids and protein-based antigen arrays in order to characterize autoreactive antibodies in neuropsychiatric systemic lupus erythematosus. We confirmed the benefits of using synthetic oligonucleotides such as assay reproducibility, elevated affinity and specificity to autoreactive antibodies. We also demonstrated presence of autoantibodies towards three particular synthetic double stranded antigens and verify similarity of antinuclear antibody patterns in ordinary lupus and neuropsychiatric systemic lupus erythematosus.

Background Anti-DNA/N-methyl-D-aspartate receptor 2 (NR2) antibodies (anti-DNA/NR2 antibodies) are a subset of anti-DNA autoantibodies that cross-react with the extracellular domain of the GluN2A/GluN2B subunits of NR2. These antibodies induce apoptosis of hippocampus neurons and psychiatric disorder in mice and humans. Neuropsychiatric system lupus erythematosus (NPSLE) can develop after initiation of corticosteroids (post-steroid neuropsychiatric manifestation: PSNP) or before treatment (de novo NPSLE); however, pathophysiological differences between these subtypes remain unclear. The objective of this study was to clarify the prevalence of anti-DNA/NR2 antibodies in patients with NPSLE. Methods This study involved a cohort of patients with NPSLE admitted to our hospital. NPSLE patients were classified into two groups, de novo NPSLE and PSNP-SLE. Serum anti-DNA antibodies and anti-DNA/NR2 antibodies were measured by enzyme-linked immunosorbent assays. Results Serum samples were obtained from 24 patients with de novo NPSLE, 25 with PSNP-SLE and 76 healthy controls (HC). The level of anti-DNA/NR2 antibodies in patients with de novo NPSLE and PSNP-SLE were also higher than those in HC. Positive correlation between anti-DNA antibodies and anti-DNA/NR2 antibodies were found in PSNP-SLE, but was not significant in de novo NPSLE. Conclusion The levels of anti-DNA/NR2 antibodies in PSNP-SLE were similar to those in de novo NPSLE. Anti-DNA/NR2 antibodies in PSNP-SLE were suggested as a dominant subset of anti-DNA antibodies, indicating that anti-DNA/NR2 antibodies may be a predictive factor in PSNP-SLE.

Este trabalho apresenta uma análise realizada na literatura acerca das Doenças Crônicas Não Transmissíveis (DCNTs) e visa analisar o risco da Apolipoproteína “E” (ApoE) e o Acidente vascular cerebral (AVC) na comunidade contemporânea. Tem seu objetivo analisar a relação entre polimorfismo da ApoE e AVC fundado na análise do risco entre o polimorfismo genético da ApoE e o AVC. Este estudo é do tipo descritivo, exploratório e com abordagem qualitativa. Conclui-se que vários autores em seu estudo relatam o risco aumentado de AVC com a ApoE e seus alelos., Este trabajo presenta un análisis realizado en la literatura acerca de las Enfermedades Crónicas no Transmisibles (DCNTs) y pretende analizar el riesgo de la Apolipoproteína "E" (ApoE) y el Accidente vascular cerebral (AVC) en la comunidad contemporánea. Tiene su objetivo analizar la relación entre polimorfismo de la ApoE y AVC fundado en el análisis del riesgo entre el polimorfismo genético de la ApoE y el AVC. Este estudio es del tipo descriptivo, exploratorio y con abordaje cualitativo Se concluye que varios autores en su estudio relatan el riesgo aumentado de AVC con la Apoy y sus alelos., This paper presents an analysis of noncommunicable chronic diseases (CDNTs) in the literature and aims to analyze the risk of Apolipoprotein E (ApoE) and stroke in the contemporary community. Its objective is to analyze the relationship between Apolipoprotein E and Stroke polymorphism based on the risk analysis between ApoE and Stroke genetic polymorphism. This is a descriptive, exploratory and qualitative study. It is concluded that several authors in their study report the increased risk of stroke with ApoE and its alleles.

Objective: to identify circulating myelin oligodendrocyte glycoprotein (MOG)-specific B cells in the blood of patients with MOG antibodies (Abs) and to determine whether circulating MOG-specific B cells are linked to levels and epitope specificity of serum anti-MOG-Abs. Methods: we compared peripheral blood from 21 patients with MOG-Abs and 26 controls for the presence of MOG-specific B cells. We differentiated blood-derived B cells in vitro in separate culture wells to Ab-producing cells via engagement of Toll-like receptors 7 and 8. We quantified the anti-MOG reactivity with a live cell-based assay by flow cytometry. We determined the recognition of MOG epitopes with a panel of mutated variants of MOG. Results: MOG-Ab-positive patients had a higher frequency of MOG-specific B cells in blood than controls, but MOG-specific B cells were only detected in about 60% of these patients. MOG-specific B cells in blood showed no correlation with anti-MOG Ab levels in serum, neither in the whole group nor in the untreated patients. Epitope analysis of MOG-Abs secreted from MOG-specific B cells cultured in different wells revealed an intraindividual heterogeneity of the anti-MOG autoimmunity. Conclusions: This study shows that patients with MOG-Abs greatly differ in the abundance of circulating MOG-specific B cells, which are not linked to levels of MOG-Abs in serum suggesting different sources of MOG-Abs. Identification of MOG-specific B cells in blood could be of future relevance for selecting patients with MOG-Abs for B cell-directed therapy., DFG; Munich Cluster for Systems Neurology EXC 1010 SyNergy and EXC 2145 SyNergy; Clinical Competence Network for Multiple Sclerosis; European Academy of Neurology; Scientific and Technological Research Council of Turkey (TÜBİTAK) 2219 Program; Alexander von Humboldt Foundation; Werner Reichenberger Stiftung; Verein zur Therapieforschung fur Multiple Sklerose-Kranke