The Protective Role of HLA-DRB1(∗)13 in Autoimmune Diseases.
The Protective Role of HLA-DRB1(∗)13 in Autoimmune Diseases.
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DOI：
10.1155/2015/948723
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发表时间：
2015
影响因子：
4.1
通讯作者：
da Silva BM
中科院分区：
文献类型：
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作者：
Bettencourt A;Carvalho C;Leal B;Brás S;Lopes D;Martins da Silva A;Santos E;Torres T;Almeida I;Farinha F;Barbosa P;Marinho A;Selores M;Correia J;Vasconcelos C;Costa PP;da Silva BM
自身免疫性疾病（AIDS）的特点是多因素病因和复杂的遗传背景，其中MHC区域起主要作用。我们对1228例艾滋病患者进行了HLA-DRB 1基因分型，其中213例为系统性红斑狼疮（SLE），166例为银屑病或银屑病关节炎（Ps + PsA），153例为风湿性关节炎（RA），67例为系统性硬化症（SSc），536例为多发性硬化症（MS），93例为重症肌无力（MG），282例为无关对照。我们证实了先前建立的HLA-DRB 1基因15（OR = 2.17）和HLA-DRB 1等位基因（OR = 1.81）等位基因与MS、HLA-DRB 1等位基因与SLE相关（OR = 2.49），HLA-DRB1 ≥ 01（OR = 1.79）和HLA-DRB 1等位基因04（OR = 2.81）RA、HLA-DRB1 + PsA HLA-DRB 1等位基因与SSc相关（OR = 1.79），与HLA-DRB 1等位基因相关（OR = 2.28），与HLA-DRB 1等位基因相关（OR = 3.01），与MG相关（OR = 2.98）。我们进一步观察到HLA-DRB 1等位基因与SLE、Ps + PsA、RA和SSc的一致负相关（分别为18.3%、19.3%、16.3%和11.9%，对照组为29.8%。AIDS组HLA-DRB 1等位基因频率为20.0%（OR = 0.58）。尽管不同的等位基因与特定的艾滋病相关，但同一等位基因HLA-DRB 1 - 13在所有分析的六种疾病中的代表性不足。这一观察结果表明，该等位基因可能赋予艾滋病，特别是全身性和风湿性疾病的保护。HLA-DRB 1 β 13的保护作用可以通过这些分子更有效的抗原呈递来解释，有利于胸腺选择过程中的有效克隆删除。
Autoimmune diseases (AIDs) are characterized by a multifactorial aetiology and a complex genetic background, with the MHC region playing a major role. We genotyped for HLA-DRB1 locus 1228 patients with AIDs-213 with Systemic Lupus Erythematosus (SLE), 166 with Psoriasis or Psoriatic Arthritis (Ps + PsA), 153 with Rheumatoid Arthritis (RA), 67 with Systemic Sclerosis (SSc), 536 with Multiple Sclerosis (MS), and 93 with Myasthenia Gravis (MG) and 282 unrelated controls. We confirmed previously established associations of HLA-DRB1∗15 (OR = 2.17) and HLA-DRB1∗03 (OR = 1.81) alleles with MS, HLA-DRB1∗03 with SLE (OR = 2.49), HLA-DRB1∗01 (OR = 1.79) and HLA-DRB1∗04 (OR = 2.81) with RA, HLA-DRB1∗07 with Ps + PsA (OR = 1.79), HLA-DRB1∗01 (OR = 2.28) and HLA-DRB1∗08 (OR = 3.01) with SSc, and HLA-DRB1∗03 with MG (OR = 2.98). We further observed a consistent negative association of HLA-DRB1∗13 allele with SLE, Ps + PsA, RA, and SSc (18.3%, 19.3%, 16.3%, and 11.9%, resp., versus 29.8% in controls). HLA-DRB1∗13 frequency in the AIDs group was 20.0% (OR = 0.58). Although different alleles were associated with particular AIDs, the same allele, HLA-DRB1∗13, was underrepresented in all of the six diseases analysed. This observation suggests that this allele may confer protection for AIDs, particularly for systemic and rheumatic disease. The protective effect of HLA-DRB1∗13 could be explained by a more proficient antigen presentation by these molecules, favouring efficient clonal deletion during thymic selection.