ArticleJournal of neuroinflammation2016
Latitude and HLA-DRB1*04:05 independently influence disease severity in Japanese multiple sclerosis: a cross-sectional study.
Article in Journal of neuroinflammation, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers, 1 of them a synthesis that pooled it.
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Who cites it
17 citing papers in PubMed, 1 synthesis or guideline pooled it, 36 citations in OpenAlex.
- The HLA paradox across populations in multiple sclerosis progression: a systematic review.BMC neurology · 2026Pooled it
- The Burden of Multiple Sclerosis in Japan from 1990 to 2021 and Predictions to 2050 Based on the Global Burden of Disease Study 2021.Neuroepidemiology · 2026Article
- Oral health in professional Slovak soccer players: Assessment of dental risks, subgingival microbiota and genetic influences.PloS one · 2026Article
- Diagnosing and Managing Uveitis Associated with Immune Checkpoint Inhibitors: A Review.Diagnostics (Basel, Switzerland) · 2024Review
- Cerebrospinal fluid oligoclonal bands in Chinese patients with multiple sclerosis: the prevalence and its association with clinical features.Frontiers in immunology · 2023Article
- Genetics of neurosarcoidosis.Journal of neuroimmunology · 2022Review
- Association of Latitude and Exposure to Ultraviolet B Radiation With Severity of Multiple Sclerosis: An International Registry Study.Neurology · 2022Observational
- Genetics and functional genomics of multiple sclerosis.Seminars in immunopathology · 2022Review
- HLA genotype-clinical phenotype correlations in multiple sclerosis and neuromyelitis optica spectrum disorders based on Japan MS/NMOSD Biobank data.Scientific reports · 2021Article
- Sunlight exposure exerts immunomodulatory effects to reduce multiple sclerosis severity.Proceedings of the National Academy of Sciences of the United States of America · 2021Article
- A new clustering method identifies multiple sclerosis-specific T-cell receptors.Annals of clinical and translational neurology · 2021Article
- Association of HLA-DRB1*04:05 allele with drug-induced interstitial lung disease in Japanese population.The pharmacogenomics journal · 2020Article
- Two susceptible HLA-DRB1 alleles for multiple sclerosis differentially regulate anti-JC virus antibody serostatus along with fingolimod.Journal of neuroinflammation · 2020Article
- Contribution of cortical lesions to cognitive impairment in Japanese patients with multiple sclerosis.Scientific reports · 2020Article
- Next-generation sequencing identifies contribution of both class I and II HLA genes on susceptibility of multiple sclerosis in Japanese.Journal of neuroinflammation · 2019Article
- A comparison of brain magnetic resonance imaging lesions in multiple sclerosis by race with reference to disability progression.Journal of neuroinflammation · 2018Article
- The Rare Disease Bank of Japan: establishment, current status and future challenges.Human cell · 2018Article
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Authors and funding
17 authors at 6 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundHigher latitude and human leukocyte antigen (HLA)-DRB1*04:05 increase susceptibility to multiple sclerosis (MS) in the Japanese population, but their effects on disease severity are unknown. We aimed to clarify the effects of latitude and the HLA-DRB1 and HLA-DPB1 genes on disease severity in Japanese patients with MS.
methodsWe enrolled 247 MS patients and 159 healthy controls (HCs) from the northernmost main island of Japan, Hokkaido Island (42-45° north), and 187 MS patients and 235 HCs from the southern half (33-35° north) of the Japanese archipelago (33-45° north). We genotyped HLA-DRB1 and HLA-DPB1 alleles, compared demographic features, and analyzed factors contributing to differences in clinical and laboratory findings between MS patients from southern and northern Japan. The Multiple Sclerosis Severity Score (MSSS), which adjusts the Kurtzke's Expanded Disability Status Scale score according to disease duration, was used to estimate disease severity.
resultsThe HLA-DRB1*04:05 and DRB1*15:01 alleles conferred susceptibility to MS in our Japanese population (p (corr) = 0.0004 and p (corr) = 0.0019, respectively). Southern patients had higher MSSS scores than northern patients (p = 0.003). Northern patients had higher frequencies of brain lesions meeting the Barkhof criteria (Barkhof brain lesions) and cerebrospinal fluid (CSF) IgG abnormalities than southern patients (p = 0.0012 and p < 0.0001, respectively). DRB1*04:05-positive MS patients had lower MSSS scores and lower frequencies of Barkhof brain lesions and CSF IgG abnormalities than DRB1*04:05-negative MS patients (p = 0.0415, p = 0.0026, and p < 0.0001, respectively). Multivariate analyses revealed that latitude and DRB1*04:05 were independently associated with the lowest quartile of MSSS and that latitude was positively associated with Barkhof brain lesions and CSF IgG abnormalities. DRB1*04:05 was negatively associated with these parameters. MSSS was decreased by 0.57 per DRB1*04:05 allele (p = 0.0198).
conclusionsLiving at a higher latitude and carrying the DRB1*04:05 allele independently lessens MS symptom severity as defined by MSSS. However, these factors influence the frequency of Barkhof brain lesions and CSF IgG abnormalities in opposite ways; higher latitude increases the frequency of Barkhof brain lesions and CSF IgG abnormalities, whereas DRB1*04:05 decreases them.
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