Dataset Information

HLA genotype-clinical phenotype correlations in multiple sclerosis and neuromyelitis optica spectrum disorders based on Japan MS/NMOSD Biobank data.

ABSTRACT: HLA genotype-clinical phenotype correlations are not established for multiple sclerosis (MS) and neuromyelitis optica spectrum disorders (NMOSD). We studied HLA-DRB1/DPB1 genotype-phenotype correlations in 528 MS and 165 NMOSD cases using Japan MS/NMOSD Biobank materials. HLA-DRB1*04:05, DRB1*15:01 and DPB1*03:01 correlated with MS susceptibility and DRB1*01:01, DRB1*09:01, DRB1*13:02 and DPB1*04:01 were protective against MS. HLA-DRB1*15:01 was associated with increased optic neuritis and cerebellar involvement and worsened visual and pyramidal functional scale (FS) scores, resulting in higher progression index values. HLA-DRB1*04:05 was associated with younger onset age, high visual FS scores, and a high tendency to develop optic neuritis. HLA-DPB1*03:01 increased brainstem and cerebellar FS scores. By contrast, HLA-DRB1*01:01 decreased spinal cord involvement and sensory FS scores, HLA-DRB1*09:01 decreased annualized relapse rate, brainstem involvement and bowel and bladder FS scores, and HLA-DRB1*13:02 decreased spinal cord and brainstem involvement. In NMOSD, HLA-DRB1*08:02 and DPB1*05:01 were associated with susceptibility and DRB1*09:01 was protective. Multivariable analysis revealed old onset age, long disease duration, and many relapses as independent disability risks in both MS and NMOSD, and HLA-DRB1*15:01 as an independent risk only in MS. Therefore, both susceptibility and protective alleles can influence the clinical manifestations in MS, while such genotype-phenotype correlations are unclear in NMOSD.

SUBMITTER: Watanabe M

PROVIDER: S-EPMC7804194 | biostudies-literature | 2021 Jan

REPOSITORIES: biostudies-literature

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HLA genotype-clinical phenotype correlations in multiple sclerosis and neuromyelitis optica spectrum disorders based on Japan MS/NMOSD Biobank data.

Watanabe Mitsuru M Nakamura Yuri Y Sato Shinya S Niino Masaaki M Fukaura Hikoaki H Tanaka Masami M Ochi Hirofumi H Kanda Takashi T Takeshita Yukio Y Yokota Takanori T Nishida Yoichiro Y Matsui Makoto M Nagayama Shigemi S Kusunoki Susumu S Miyamoto Katsuichi K Mizuno Masanori M Kawachi Izumi I Saji Etsuji E Ohashi Takashi T Shimohama Shun S Hisahara Shin S Nishiyama Kazutoshi K Iizuka Takahiro T Nakatsuji Yuji Y Okuno Tatsusada T Ochi Kazuhide K Suzumura Akio A Yamamoto Ken K Kawano Yuji Y Tsuji Shoji S Hirata Makoto M Sakate Ryuichi R Kimura Tomonori T Shimizu Yuko Y Nagaishi Akiko A Okada Kazumasa K Hayashi Fumie F Sakoda Ayako A Masaki Katsuhisa K Shinoda Koji K Isobe Noriko N Matsushita Takuya T Kira Jun-Ichi JI

Scientific reports 20210112 1

HLA genotype-clinical phenotype correlations are not established for multiple sclerosis (MS) and neuromyelitis optica spectrum disorders (NMOSD). We studied HLA-DRB1/DPB1 genotype-phenotype correlations in 528 MS and 165 NMOSD cases using Japan MS/NMOSD Biobank materials. HLA-DRB1*04:05, DRB1*15:01 and DPB1*03:01 correlated with MS susceptibility and DRB1*01:01, DRB1*09:01, DRB1*13:02 and DPB1*04:01 were protective against MS. HLA-DRB1*15:01 was associated with increased optic neuritis and cereb ...[more]

PMID: 33436735

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Project description:BackgroundNeuromyelitis Optica Spectrum Disorder (NMOSD) is an inflammatory disease of the central nervous system with preferential involvement of the optic nerve and spinal cord. However, data on NMOSD incidences in China, a country encompassing 20% of the world's population and covering vast areas of Eastern Asia, are unknown.MethodsWe conducted the first nationwide survey of NMOSD, based on the database of the National Hospital Quality Monitoring System (HQMS) of China, which covers all 1665 tertiary hospitals. The "Medical Record Homepage" of all patients were consistently collected via a standard protocol across each tertiary hospital. The primary outcome was the incidence of NMOSD, diagnosed according to the 2015 International Panel for Neuromyelitis Optica Diagnosis criteria and identified by ICD-10 code (G36•0). Burden of hospitalization, comorbidities, and death were also evaluated.FindingsWe identified 33,489 hospital admissions for 17,416 NMOSD diagnosed patients from 2016 to 2018. 11,973 patients were newly diagnosed NMOSD. The age and sex adjusted incidence per 100,000 person years was 0•278 (95% confidence interval [CI], 0•273-0•283), with 0•075 (0•069-0•08) in child and 0•347 (0•34-0•353) in adult. The peak age of onset NMOSD is 45-65 years with an incidence 0•445/100,000 (95% CI, 0•433-0•457). The female to male ratio was 4•71 (p<0•001, 95% CI, 4•50-4•94). Geographical distribution of NMOSD is not related to the latitude gradient. Sjögren's syndrome (1,124/17,416, 6•5%) and systemic lupus erythematosus (387/17,416, 2•2%) are the most frequently autoimmune comorbidities. 106 adults and 4 children of the 17,416 NMOSD cohort died.InterpretationThe incidence of NMOSD in China per 100,000 person years was 0•278, with 0•075 in child and 0•347 in adult. The geographical distribution of NMOSD is not related to the latitude gradient.FundingNational Science Foundation of China (91949208, 91642205, and 81830038); Advanced Innovation Center for Human Brain Protection, Capital Medical University, Beijing.

Project description:BACKGROUND AND PURPOSE:Both clinical and imaging criteria must be met to diagnose neuromyelitis optica spectrum disorders and multiple sclerosis. However, neuromyelitis optica spectrum disorders are often misdiagnosed as MS because of an overlap in MR imaging features. The purpose of this study was to confirm imaging differences between neuromyelitis optica spectrum disorders and MS with visually detailed quantitative analyses of large-sample data. MATERIALS AND METHODS:We retrospectively examined 89 consecutive patients with neuromyelitis optica spectrum disorders (median age, 51 years; range, 16-85 years; females, 77; aquaporin 4 immunoglobulin G-positive, 93%) and 89 with MS (median age, 36 years; range, 18-67 years; females, 68; relapsing-remitting MS, 89%; primary-progressive MS, 7%; secondary-progressive MS, 2%) from 9 institutions across Japan (April 2008 to December 2012). Two neuroradiologists visually evaluated the number, location, and size of all lesions using the Mann-Whitney U test or the Fisher exact test. RESULTS:We enrolled 79 patients with neuromyelitis optica spectrum disorders and 87 with MS for brain analysis, 57 with neuromyelitis optica spectrum disorders and 55 with MS for spinal cord analysis, and 42 with neuromyelitis optica spectrum disorders and 14 with MS for optic nerve analysis. We identified 911 brain lesions in neuromyelitis optica spectrum disorders, 1659 brain lesions in MS, 86 spinal cord lesions in neuromyelitis optica spectrum disorders, and 102 spinal cord lesions in MS. The frequencies of periventricular white matter and deep white matter lesions were 17% and 68% in neuromyelitis optica spectrum disorders versus 41% and 42% in MS, respectively (location of brain lesions, P < .001). We found a significant difference in the distribution of spinal cord lesions between these 2 diseases (P = .024): More thoracic lesions than cervical lesions were present in neuromyelitis optica spectrum disorders (cervical versus thoracic, 29% versus 71%), whereas they were equally distributed in MS (46% versus 54%). Furthermore, thoracic lesions were significantly longer than cervical lesions in neuromyelitis optica spectrum disorders (P = .001), but not in MS (P = .80). CONCLUSIONS:Visually detailed quantitative analyses confirmed imaging differences, especially in brain and spinal cord lesions, between neuromyelitis optica spectrum disorders and MS. These observations may have clinical implications.

Dataset Information

HLA genotype-clinical phenotype correlations in multiple sclerosis and neuromyelitis optica spectrum disorders based on Japan MS/NMOSD Biobank data.

Publications

HLA genotype-clinical phenotype correlations in multiple sclerosis and neuromyelitis optica spectrum disorders based on Japan MS/NMOSD Biobank data.

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