The HLA profiles of mixed connective tissue disease differ distinctly from the profiles of clinically related connective tissue diseases
The HLA profiles of mixed connective tissue disease differ distinctly from the profiles of clinically related connective tissue diseases
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DOI：
10.1093/rheumatology/keu310
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发表时间：
2015-03-01
期刊：
影响因子：
5.5
通讯作者：
Molberg, Oyvind
中科院分区：
文献类型：
--
作者：
Flam, Siri Tennebo;Gunnarsson, Ragnar;Molberg, Oyvind
客观的。挪威全国 MCTD 队列的建立是为了获得有关关键疾病问题的公正数据，从而重新评估 MCTD 的概念。在当前的研究中，目的是获得挪威大型 MCTD 队列的详细 HLA 谱数据，并将这些数据与种族匹配的健康对照和相关 CTD 对照的 HLA 谱进行比较。方法。通过基于序列的 HLA-B-star 和 DRB1(star) 分型确定的 HLA 谱在挪威血统、SLE (n = 96)、SSc (n = 95)、PM/DM (n = 84)、健康个体 (n = 282)、完整 MCTD 队列 (n = 155) 和由关键临床参数定义的 MCTD 子集的四个对照组之间进行比较。结果。 HLA-B-star 08 [比值比 (OR) 2.05, P = 1.31 x 10(-4)) 和 DRB1(star) 04: 01 (OR 2.82, P = 3.64 x 10(-8)) 被确定为 MCTD 的风险等位基因，而 DRB1(star) 04: 04, DRB1(star) 13: 01和 DRB1(star) 13: 02 具有保护作用。 SLE 和 PM/DM 的风险等位基因为 B(star)08 和 DRB1(star)03:01。 SSc 风险与 DRB1(star) 08: 01 相关。MCTD 子集的分析确定 B(star)18 [OR 3.32 (95% CI 1.38, 8.01)] 和 DRB1(star)03: 01 [OR 1.83 (95% CI 1.03, 3.25)] 是肺纤维化的独立危险因素。结论。鉴定出与 MCTD 和疾病亚群相关的新 HLA 等位基因，并确认 DRB1(star) 04: 01 为主要风险等位基因。总而言之，这些数据强化了 MCTD 作为一种不同于 SLE、SSc 和 PM/DM 的疾病实体的概念。
Objective. The Norwegian nationwide MCTD cohort was established to obtain unbiased data on key disease issues, and thereby reappraise the concept of MCTD. In the current study, the aims were to obtain detailed HLA profile data on the large Norwegian MCTD cohort and compare these with the HLA profiles of ethnically matched healthy controls and related CTD controls.Methods. HLA profiles, determined by sequence-based typing of HLA-B-star and DRB1(star), were compared between four control groups of Norwegian ancestry, SLE (n = 96), SSc (n = 95), PM/DM (n = 84), healthy individuals (n = 282), the complete MCTD cohort (n = 155) and MCTD subsets defined by key clinical parameters.Results. HLA-B-star 08 [odds ratio (OR) 2.05, P = 1.31 x 10(-4)) and DRB1(star) 04: 01 (OR 2.82, P = 3.64 x 10(-8)) were identified as risk alleles for MCTD, while DRB1(star) 04: 04, DRB1(star) 13: 01 and DRB1(star) 13: 02 were protective. Risk alleles for SLE and PM/DM were B(star)08 and DRB1(star)03:01. SSc risk was associated with DRB1(star) 08: 01. Analyses of MCTD subsets identified B(star)18 [OR 3.32 (95% CI 1.38, 8.01)] and DRB1(star)03: 01 [OR 1.83 (95% CI 1.03, 3.25)] as independent risk factors for lung fibrosis.Conclusion. Novel HLA alleles associated with MCTD and disease subsets were identified and DRB1(star) 04: 01 was confirmed as a major risk allele. Altogether, the data reinforce the notion of MCTD as a disease entity distinct from SLE, SSc and PM/DM.