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Neuromyelitis optica is an HLA associated disease different from Multiple Sclerosis: a systematic review with meta-analysis.

ABSTRACT: Neuromyelitis Optica and Multiple Sclerosis are idiopathic inflammatory demyelinating diseases of the central nervous system that currently are considered distinct autoimmune diseases, so differences in genetic susceptibility would be expected. This study aimed to investigate the HLA association with Neuromyelitis Optica by a systematic review with meta-analysis. The STROBE instrument guided research paper assessments. Thirteen papers published between 2009 and 2020 were eligible. 568 Neuromyelitis Optica patients, 41.4% Asians, 32.4% Latin Americans and 26.2% Europeans were analyzed. Only alleles of the DRB1 locus were genotyped in all studies. Neuromyelitis Optica patients have 2.46 more chances of having the DRB1*03 allelic group than controls. Ethnicity can influence genetic susceptibility. The main HLA association with Neuromyelitis Optica was the DRB1*03:01 allele in Western populations and with the DPB1*05:01 allele in Asia. Differences in the Multiple Sclerosis and Neuromyelitis Optica genetic susceptibility was confirmed in Afro descendants. The DRB1*03 allelic group associated with Neuromyelitis Optica has also been described in other systemic autoimmune diseases.

SUBMITTER: Alvarenga MP

PROVIDER: S-EPMC7794341 | biostudies-literature | 2021 Jan

REPOSITORIES: biostudies-literature

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Neuromyelitis optica is an HLA associated disease different from Multiple Sclerosis: a systematic review with meta-analysis.

Alvarenga Marcos Papais MP do Carmo Luciana Ferreira LF Vasconcelos Claudia Cristina Ferreira CCF Alvarenga Marina Papais MP Alvarenga-Filho Helcio H de Melo Bento Cleonice Alves CA Paiva Carmen Lucia Antão CLA Leyva-Fernández Laura L Fernández Óscar Ó Papais-Alvarenga Regina Maria RM

Scientific reports 20210108 1

Neuromyelitis Optica and Multiple Sclerosis are idiopathic inflammatory demyelinating diseases of the central nervous system that currently are considered distinct autoimmune diseases, so differences in genetic susceptibility would be expected. This study aimed to investigate the HLA association with Neuromyelitis Optica by a systematic review with meta-analysis. The STROBE instrument guided research paper assessments. Thirteen papers published between 2009 and 2020 were eligible. 568 Neuromyeli ...[more]

PMID: 33420337

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Project description:BackgroundMultiple sclerosis (MS) and neuromyelitis optica (NMO) occasionally have an extremely aggressive and debilitating disease course; however, its molecular basis is unknown. This study aimed to determine a relationship between connexin (Cx) pathology and disease aggressiveness in Asian patients with MS and NMO.Methods/principal findingsSamples included 11 autopsied cases with NMO and NMO spectrum disorder (NMOSD), six with MS, and 20 with other neurological diseases (OND). Methods of analysis included immunohistochemical expression of astrocytic Cx43/Cx30, oligodendrocytic Cx47/Cx32 relative to AQP4 and other astrocytic and oligodendrocytic proteins, extent of demyelination, the vasculocentric deposition of complement and immunoglobulin, and lesion staging by CD68 staining for macrophages. Lesions were classified as actively demyelinating (n=59), chronic active (n=58) and chronic inactive (n=23). Sera from 120 subjects including 30 MS, 30 NMO, 40 OND and 20 healthy controls were examined for anti-Cx43 antibody by cell-based assay. Six NMO/NMOSD and three MS cases showed preferential loss of astrocytic Cx43 beyond the demyelinated areas in actively demyelinating and chronic active lesions, where heterotypic Cx43/Cx47 astrocyte oligodendrocyte gap junctions were extensively lost. Cx43 loss was significantly associated with a rapidly progressive disease course as six of nine cases with Cx43 loss, but none of eight cases without Cx43 loss regardless of disease phenotype, died within two years after disease onset (66.7% vs. 0%, P=0.0090). Overall, five of nine cases with Cx43 loss and none of eight cases without Cx43 loss had distal oligodendrogliopathy characterized by selective myelin associated glycoprotein loss (55.6% vs. 0.0%, P=0.0296). Loss of oligodendrocytic Cx32 and Cx47 expression was observed in most active and chronic lesions from all MS and NMO/NMOSD cases. Cx43-specific antibodies were absent in NMO/NMOSD and MS patients.ConclusionsThese findings suggest that autoantibody-independent astrocytic Cx43 loss may relate to disease aggressiveness and distal oligodendrogliopathy in both MS and NMO.

Dataset Information

Neuromyelitis optica is an HLA associated disease different from Multiple Sclerosis: a systematic review with meta-analysis.

Publications

Neuromyelitis optica is an HLA associated disease different from Multiple Sclerosis: a systematic review with meta-analysis.

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