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06.05.2022 | Original Article

HLA-DQB105:02, 05:03, and *03:01 alleles as risk factors for myasthenia gravis in a Spanish cohort

verfasst von: Maria Salvado, Jose Luis Caro, Cecilia Garcia, Francesc Rudilla, Laura Zalba-Jadraque, Eva Lopez, Elia Sanjuan, Josep Gamez, Jose Manuel Vidal-Taboada

Erschienen in: Neurological Sciences | Ausgabe 8/2022

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Abstract

Background

Myasthenia gravis (MG) is a very heterogenic chronic autoimmune disease caused by the failure of neuromuscular transmission. The HLA gene complex has conventionally been recognized as its main genetic risk and phenotype modifying factor. Our aim was to investigate the prevalence of HLA class I and II alleles and to identify possible risk factors for sporadic MG in a Spanish cohort.

Methods

We designed a clinical case–control study comparing HLA alleles and haplotype frequencies in a cohort of 234 patients with sporadic autoimmune MG with data from a group of 492 randomly selected healthy subjects. Using a high-resolution next-generation sequencing (NGS)–based HLA genotyping assay, we investigated the contribution of HLA genotypes and haplotypes in the resulting phenotype, especially, the age at onset, sex, onset MGFA class, thymic histopathology, and serological status.

Results

We found that the DQB1*05:02 and DQB1*05:03 alleles could be novel risk factors for Spanish MG cases. The HLA alleles A*01:01, B*08:01, DRB1*03:01, DRB1*14:54, and DQB1*02:01 were also risk factors for the disease. DQB1*03:01 acted as a risk factor for EOMG in women with AChR-positive antibodies and thymus hyperplasia. Additionally, several alleles were identified as potential phenotype-modifying factors that could exert a protective effect: HLA-B*35:08, DRB1*13:01, and DQB1*06:03 in MG; HLA-A*24:02 in women and DRB1*07:01 and DQB1*02:02 for early onset. HLA-C*07:01 and haplotype A1-B8-C7-DR3-DQ2 were associated with an early-onset phenotype.

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Titel: HLA-DQB1*05:02, *05:03, and *03:01 alleles as risk factors for myasthenia gravis in a Spanish cohort
verfasst von: Maria Salvado
Jose Luis Caro
Cecilia Garcia
Francesc Rudilla
Laura Zalba-Jadraque
Eva Lopez
Elia Sanjuan
Josep Gamez
Jose Manuel Vidal-Taboada
Publikationsdatum: 06.05.2022
Verlag: Springer International Publishing
Erschienen in: Neurological Sciences / Ausgabe 8/2022
Print ISSN: 1590-1874
Elektronische ISSN: 1590-3478
DOI: https://doi.org/10.1007/s10072-022-06102-y

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