瑞典多发性硬化症患者的高分辨率HLAⅱ类测序

IF 2.3 4区医学 Q3 GENETICS & HEREDITY

International Journal of Immunogenetics Pub Date : 2022-08-12 DOI:10.1111/iji.12594

Omar Akel, Lue Ping Zhao, Daniel E Geraghty, Alexander Lind

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引用次数: 0

摘要

多发性硬化症(MS)是一种慢性神经系统疾病，被认为是由自身免疫机制引起的。病因可能是遗传和环境因素之间复杂的相互作用。对多发性硬化症的遗传研究已经进行了50多年，迄今为止产生了100种关联。在全球范围内，最强的连锁是与人类白细胞抗原(HLA) HLA- drb5 *01:01:01-DRB1*15:01:01-DQA1*01:02:01-DQB1*06:02:01单倍型。本文采用HLA高分辨率测序技术，对100例瑞典MS患者的DRB3、DRB4、DRB5、DRB1、DQA1、DQB1、DPA1和DPB1等位基因及其扩展单倍型和基因型进行了检测。结果与636例对照人群进行了比较。证实了HLA与MS的异质性;在100例患者中，发现延长HLA-DR-DQ基因型69例。发现3种扩展HLA-DR-DQ基因型与MS相关;HLA-DRB5*01:01:01- drb1 *15:01:01-DQA1*01:02:01-DQB1*06:02:01单倍型与(A) HLA-DRB4*01:01:01//DRB4*01:01:01 - drb1 *07:01:01-DQA1* 02:02:01，(B) HLA-DRBX*null-DRB1*08:01:01-DQA1*04:01:01-DQB1*04:02:01，和(C) HLA-DRB3*01:01:02-DRB1*03:01:01-DQA1*05:01:01-DQB1*02:01:01。在等位基因水平上，HLA-DRB3*01:01:02被认为对ms具有保护作用，然而，当与HLA-DRB3*01:01:02- drb1 *03:01:01-DQA1*05:01:01-DQB1*02:01:01联合使用时，该扩展单倍型被认为是易感危险因素。这突出了与扩展单倍型/基因型相比，单等位基因研究的局限性。总之，100名患者中有69个基因型，我们进行了高分辨率测序，以强调MS患者中存在的广泛多态性。在更大的队列中进行更多的研究对于在与HLA-DRB5*01:01:01-DRB1*15:01:01-DQA1*01:02:01-DQB1*06:02:01无关的患者组中定义MS将是重要的。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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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

(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

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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来源期刊

International Journal of Immunogenetics 医学-免疫学

CiteScore

4.70

自引率

0.00%

发文量

审稿时长

6-12 weeks

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.