Omar Akel, Lue Ping Zhao, Daniel E Geraghty, Alexander Lind
{"title":"瑞典多发性硬化症患者的高分辨率HLAⅱ类测序","authors":"Omar Akel, Lue Ping Zhao, Daniel E Geraghty, Alexander Lind","doi":"10.1111/iji.12594","DOIUrl":null,"url":null,"abstract":"<p>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) <i>HLA-DRB5*01:01:01-DRB1*15:01:01-DQA1*01:02:01-DQB1*06:02:01</i> haplotype.</p><p>Here, high-resolution sequencing of HLA was used to determine the alleles of <i>DRB3</i>, <i>DRB4</i>, <i>DRB5</i>, <i>DRB1</i>, <i>DQA1</i>, <i>DQB1</i>, <i>DPA1</i> and <i>DPB1</i> as well as their extended haplotypes and genotypes in 100 Swedish MS patients. Results were compared to 636 population controls.</p><p>The heterogeneity in HLA associations with MS was demonstrated; among 100 patients, 69 extended <i>HLA-DR-DQ</i> genotypes were found. Three extended <i>HLA-DR-DQ</i> genotypes were found to be correlated to MS; <i>HLA-DRB5*01:01:01-DRB1*15:01:01-DQA1*01:02:01-DQB1*06:02:01</i> haplotype together with</p><p>(A) <i>HLA-DRB4*01:01:01//DRB4*01:01:01:01-DRB1*07:01:01-DQA1*02:01//02:01:01-DQB1*02:02:01</i>,</p><p>(B) <i>HLA-DRBX*null-DRB1*08:01:01-DQA1*04:01:01-DQB1*04:02:01</i>, and</p><p>(C) <i>HLA-DRB3*01:01:02-DRB1*03:01:01-DQA1*05:01:01-DQB1*02:01:01</i>.</p><p>At the allelic level, <i>HLA-DRB3*01:01:02</i> was considered protective against MS. However, when combined with <i>HLA-DRB3*01:01:02-DRB1*03:01:01-DQA1*05:01:01-DQB1*02:01:01</i>, 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.</p><p>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 <i>HLA-DRB5*01:01:01-DRB1*15:01:01-DQA1*01:02:01-DQB1*06:02:01</i>.</p>","PeriodicalId":14003,"journal":{"name":"International Journal of Immunogenetics","volume":null,"pages":null},"PeriodicalIF":2.3000,"publicationDate":"2022-08-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9545082/pdf/","citationCount":"0","resultStr":"{\"title\":\"High-resolution HLA class II sequencing of Swedish multiple sclerosis patients\",\"authors\":\"Omar Akel, Lue Ping Zhao, Daniel E Geraghty, Alexander Lind\",\"doi\":\"10.1111/iji.12594\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p>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) <i>HLA-DRB5*01:01:01-DRB1*15:01:01-DQA1*01:02:01-DQB1*06:02:01</i> haplotype.</p><p>Here, high-resolution sequencing of HLA was used to determine the alleles of <i>DRB3</i>, <i>DRB4</i>, <i>DRB5</i>, <i>DRB1</i>, <i>DQA1</i>, <i>DQB1</i>, <i>DPA1</i> and <i>DPB1</i> as well as their extended haplotypes and genotypes in 100 Swedish MS patients. Results were compared to 636 population controls.</p><p>The heterogeneity in HLA associations with MS was demonstrated; among 100 patients, 69 extended <i>HLA-DR-DQ</i> genotypes were found. Three extended <i>HLA-DR-DQ</i> genotypes were found to be correlated to MS; <i>HLA-DRB5*01:01:01-DRB1*15:01:01-DQA1*01:02:01-DQB1*06:02:01</i> haplotype together with</p><p>(A) <i>HLA-DRB4*01:01:01//DRB4*01:01:01:01-DRB1*07:01:01-DQA1*02:01//02:01:01-DQB1*02:02:01</i>,</p><p>(B) <i>HLA-DRBX*null-DRB1*08:01:01-DQA1*04:01:01-DQB1*04:02:01</i>, and</p><p>(C) <i>HLA-DRB3*01:01:02-DRB1*03:01:01-DQA1*05:01:01-DQB1*02:01:01</i>.</p><p>At the allelic level, <i>HLA-DRB3*01:01:02</i> was considered protective against MS. However, when combined with <i>HLA-DRB3*01:01:02-DRB1*03:01:01-DQA1*05:01:01-DQB1*02:01:01</i>, 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.</p><p>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 <i>HLA-DRB5*01:01:01-DRB1*15:01:01-DQA1*01:02:01-DQB1*06:02:01</i>.</p>\",\"PeriodicalId\":14003,\"journal\":{\"name\":\"International Journal of Immunogenetics\",\"volume\":null,\"pages\":null},\"PeriodicalIF\":2.3000,\"publicationDate\":\"2022-08-12\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9545082/pdf/\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"International Journal of Immunogenetics\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://onlinelibrary.wiley.com/doi/10.1111/iji.12594\",\"RegionNum\":4,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q3\",\"JCRName\":\"GENETICS & HEREDITY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"International Journal of Immunogenetics","FirstCategoryId":"3","ListUrlMain":"https://onlinelibrary.wiley.com/doi/10.1111/iji.12594","RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q3","JCRName":"GENETICS & HEREDITY","Score":null,"Total":0}
High-resolution HLA class II sequencing of Swedish multiple sclerosis patients
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
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.
期刊介绍：
The International Journal of Immunogenetics (formerly European Journal of Immunogenetics) publishes original contributions on the genetic control of components of the immune system and their interactions in both humans and experimental animals. The term ''genetic'' is taken in its broadest sense to include studies at the evolutionary, molecular, chromosomal functional and population levels in both health and disease. Examples are:
-studies of blood groups and other surface antigens-
cell interactions and immune response-
receptors, antibodies, complement components and cytokines-
polymorphism-
evolution of the organisation, control and function of immune system components-
anthropology and disease associations-
the genetics of immune-related disease: allergy, autoimmunity, immunodeficiency and other immune pathologies-
All papers are seen by at least two independent referees and only papers of the highest quality are accepted.
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