Background:Neuromyelitis optica spectrum disorders (NMOSDs) represent 20% of all demyelinating disorders in South India. No studies have determined the seroprevalence to both antibodies against aquaporin-4* and antimyelin oligodendrocyte glycoprotein antibody (anti-MOG+) in this population.Objective:To identify and characterize seropositive patients for anti-aquaporin-4 antibody (anti-AQP4+) and anti-MOG+ in South India.Materials and Methods:We included 125 consecutive patients (15 children) who were serologically characterized using live transfected cells to human M23-AQP4 or full-length MOG.Results:Among a total of 125 patients, 30.4% of patients were anti-AQP4+, 20% were anti-MOG+, and 49.6% were seronegative. No patient was positive for both. Anti-MOG+ patients represented 28.7% (25/87) of seronegative NMOSD. In comparison to anti-AQP4+ patients, anti-MOG+ patients were commonly male, had less frequent attacks and milder disability on expanded disability status score scale. Seronegative patients were also predominantly male, 36% (9/25) had monophasic longitudinally extensive transverse myelitis and disability was comparable with anti-AQP4+ patients. Lumbar cord involvement was common in anti-MOG+ and seronegatives, whereas anti-AQP4+ patients had more cervical lesions.Conclusion:Anti-AQP4+/anti-MOG + patients accounted for nearly half of the patients suspected of having NMOSD in South India, indicating that antibody testing may be useful on the management of subgroups with different prognosis.
The results of our study indicated that serum 25(OH)D shows an inverse relationship with MS in the Indian population. Reverse causality cannot be excluded.
ObjectiveTo understand the role of gut microbiome in influencing the pathogenesis of neuromyelitis optica spectrum disorders (NMOSDs) among patients of south Indian origin.MethodsIn this case-control study, stool and blood samples were collected from 39 patients with NMOSD, including 17 with aquaporin 4 IgG antibodies (AQP4+) and 36 matched controls. 16S ribosomal RNA (rRNA) sequencing was used to investigate the gut microbiome. Peripheral CD4+ T cells were sorted in 12 healthy controls, and in 12 patients with AQP4+ NMOSD, RNA was extracted and immune gene expression was analyzed using the NanoString nCounter human immunology kit code set.ResultsMicrobiota community structure (beta diversity) differed between patients with AQP4+ NMOSD and healthy controls (p < 0.001, pairwise PERMANOVA test). Linear discriminatory analysis effect size identified several members of the microbiota that were altered in patients with NMOSD, including an increase in Clostridium bolteae (effect size 4.23, p 0.00007). C bolteae was significantly more prevalent (p = 0.02) among patients with AQP4-IgG+ NMOSD (n = 8/17 subjects) compared with seronegative patients (n = 3/22) and was absent among healthy stool samples. C bolteae has a highly conserved glycerol uptake facilitator and related aquaporin protein (p59-71) that shares sequence homology with AQP4 peptide (p92-104), positioned within an immunodominant (AQP4 specific) T-cell epitope (p91-110). Presence of C bolteae correlated with expression of inflammatory genes associated with both innate and adaptive immunities and particularly involved in plasma cell differentiation, B cell chemotaxis, and Th17 activation.ConclusionOur study described elevated levels of C bolteae associated with AQP4+ NMOSD among Indian patients. It is possible that this organism may be causally related to the immunopathogenesis of this disease in susceptible individuals.
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