ArticleInternational journal of immunogenetics2022
High-resolution HLA class II sequencing of Swedish multiple sclerosis patients.
Article in International journal of immunogenetics, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 3 papers.
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Who cites it
3 citing papers in PubMed, 4 citations in OpenAlex.
- Association of HLA-DRB1 pocket structures with susceptibility and prognosis of Graves' and Hashimoto's disease.Endocrine journal · 2026Article
- Human leukocyte antigen-DQA1*04:01 and rs2040406 variants are associated with elevated risk of childhood Burkitt lymphoma.Communications biology · 2024Article
- High-resolution HLA class II sequencing of Swedish multiple sclerosis patients.International journal of immunogenetics · 2022Article
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Authors and funding
4 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Multiple sclerosis (MS) is a chronic neurological disease believed to be caused by autoimmune pathogenesis. The aetiology is likely explained by a complex interplay between inherited and environmental factors. Genetic investigations into MS have been conducted for over 50 years, yielding >100 associations to date. Globally, the strongest linkage is with the human leukocyte antigen (HLA) HLA-DRB5*01:01:01-DRB1*15:01:01-DQA1*01:02:01-DQB1*06:02:01 haplotype. Here, high-resolution sequencing of HLA was used to determine the alleles of DRB3, DRB4, DRB5, DRB1, DQA1, DQB1, DPA1 and DPB1 as well as their extended haplotypes and genotypes in 100 Swedish MS patients. Results were compared to 636 population controls. The heterogeneity in HLA associations with MS was demonstrated; among 100 patients, 69 extended HLA-DR-DQ genotypes were found. Three extended HLA-DR-DQ genotypes were found to be correlated to MS; HLA-DRB5*01:01:01-DRB1*15:01:01-DQA1*01:02:01-DQB1*06:02:01 haplotype together with (A) HLA-DRB4*01:01:01//DRB4*01:01:01:01-DRB1*07:01:01-DQA1*02:01//02:01:01-DQB1*02:02:01, (B) HLA-DRBX*null-DRB1*08:01:01-DQA1*04:01:01-DQB1*04:02:01, and (C) HLA-DRB3*01:01:02-DRB1*03:01:01-DQA1*05:01:01-DQB1*02:01:01. At the allelic level, HLA-DRB3*01:01:02 was considered protective against MS. However, when combined with HLA-DRB3*01:01:02-DRB1*03:01:01-DQA1*05:01:01-DQB1*02:01:01, this extended haplotype was considered a predisposing risk factor. This highlights the limitations as included with investigations of single alleles relative to those of extended haplotypes/genotypes. In conclusion, with 69 genotypes presented among 100 patients, high-resolution sequencing was conducted to underscore the wide polymorphisms present among MS patients. Additional studies in larger cohorts will be of importance to define MS among the patient group not associated with HLA-DRB5*01:01:01-DRB1*15:01:01-DQA1*01:02:01-DQB1*06:02:01.
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