Screening for MOG-IgG and 27 other anti-glial and anti-neuronal autoantibodies in 'pattern II multiple sclerosis' and brain biopsy findings in a MOG-IgG-positive case.

BACKGROUND: Histopathological studies have revealed four different immunopathological patterns of lesion pathology in early multiple sclerosis (MS). Pattern II MS is characterised by immunoglobulin and complement deposition in addition to T-cell and macrophage infiltration and is more likely to respond to plasma exchange therapy, suggesting a contribution of autoantibodies. OBJECTIVE: To assess the frequency of anti-myelin oligodendrocyte glycoprotein (MOG), anti-M1-aquaporin-4 (AQP4), anti-M23-AQP4, anti-N-methyl-d-aspartate-type glutamate receptors (NMDAR) and 25 other anti-neural antibodies in pattern II MS. METHODS: Thirty-nine serum samples from patients with MS who had undergone brain biopsy (n = 24; including 13 from patients with pattern II MS) and from histopathologically non-classified MS patients (n = 15) were tested for anti-MOG, anti-M1-AQP4, anti-M23-AQP4, anti-NMDAR, anti-α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor-type glutamate receptors (AMPAR), anti-gamma-aminobutyric acid receptors (GABABR), anti-leucine-rich, glioma-activated protein 1 (LGI1), anti-contactin-associated protein 2 (CASPR2), anti-dipeptidyl-peptidase-like protein-6 (DPPX), anti-Tr/Delta/notch-like epidermal growth factor-related receptor (DNER), anti-Hu, anti-Yo, anti-Ri, anti-Ma1/Ma2, anti-CV2/collapsin response mediator protein 5 (CRMP5), anti-glutamic acid decarboxylase (GAD), anti-amphiphysin, anti-Ca/RhoGTPase-activating protein 26 (ARHGAP26), anti-Sj/inositol-1,4,5-trisphosphate receptor 1 (ITPR1), anti-Homer3, anti-carbonic anhydrase-related protein (CARPVIII), anti-protein kinase gamma (PKCgamma), anti-glutamate receptor delta 2 (GluRdelta2), anti-metabotropic glutamate receptor 1 (mGluR1) and anti-mGluR5, as well as for anti-glial nuclei antibodies (AGNA) and Purkinje cell antibody 2 (PCA2). RESULTS: Antibodies to MOG belonging to the complement-activating immunoglobulin G1 (IgG1) subclass were detected in a patient with pattern II MS. Detailed brain biopsy findings are shown. CONCLUSION: This is the largest study on established anti-neural antibodies performed in MS so far. MOG-IgG may play a role in a small percentage of patients diagnosed with pattern II MS.

Vasopressin inhibits mitogen-activated protein kinases and activated protein-1 in macrophages.

OBJECTIVES: We have previously shown that vasopressin could inhibit the upregulation of inflammatory mediators. Expression of inflammatory mediators is tightly regulated by the upstream transcriptional pathway mitogen-activated protein kinases (MAPKs) and activated protein-1 (AP-1). In this study, we elucidated whether vasopressin could inhibit the upregulation of MAPKs/AP-1. METHODS: Murine macrophages (RAW264.7 cells) randomly received lipopolysaccharide (LPS; 100 ng/mL) or LPS plus vasopressin (1000 pg/mL) (designated as the LPS and the LPS+V groups, respectively). Control groups were run simultaneously. For MAPKs, cells were harvested at 0 minutes, 15 minutes, 30 minutes, 45 minutes, and 60 minutes after reaction. For AP-1, cells were harvested at 60 minutes after reaction. Between-group differences in MAPKs (i.e., extracellular regulated kinase, c-Jun N-terminal kinase, and p38 MAPK) and AP-1 expressions were compared. RESULTS: Immunoblotting assay data revealed that extracellular regulated kinase concentrations of the LPS+V group that harvested at 45 minutes and 60 minutes, but not at 15 minutes and 30 minutes, were significantly lower than those of the LPS group (p=0.005 and p=0.013). C-Jun N-terminal kinase concentrations of the LPS+V group that harvested at 15 minutes, 30 minutes, 45 minutes, and 60 minutes were also significantly lower than those of the LPS group (all p<0.001). Concentrations of p38 MAPK of the LPS+V group that harvested at 15 minutes, 30 minutes, and 45 minutes, but not at 60 minutes, were also significantly lower than those of the LPS group (all p<0.001). In addition, immunohistochemistry assay revealed that the AP-1 fluorescence signals of the LPS+V group were weaker than those of the LPS group. CONCLUSION: Vasopressin inhibits MAPKs and AP-1 in endotoxin-activated macrophages.