Clostridium bolteae is elevated in neuromyelitis optica spectrum disorder in India and shares sequence similarity with AQP4
| Autor: | Lekha Pandit, Hrishikesh Lokhande, Chaithra Malli, Anitha D'Cunha, Timothy Rooney, Tanuja Chitnis, Laura M. Cox, Valerie Willocq, Shrishti Saxena |
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| Jazyk: | angličtina |
| Rok vydání: | 2020 |
| Předmět: |
0301 basic medicine
Neuromyelitis optica biology business.industry RNA Ribosomal RNA medicine.disease Epitope Article Pathogenesis 03 medical and health sciences 030104 developmental biology 0302 clinical medicine Aquaporin 4 Neurology Immunology Plasma cell differentiation medicine biology.protein Neurology (clinical) Antibody business 030217 neurology & neurosurgery |
| Zdroj: | Neurology® Neuroimmunology & Neuroinflammation article-version (Version of Record) 3 |
| ISSN: | 2332-7812 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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