Immunogenetic risk and protective factors for juvenile dermatomyositis in Caucasians
Immunogenetic risk and protective factors for juvenile dermatomyositis in Caucasians
复制标题
DOI：
10.1002/art.22216
复制
发表时间：
2006-12-01
影响因子：
--
通讯作者：
Rider, Lisa G.
中科院分区：
文献类型：
--
作者：
Mamyrova, Gulnara;O'Hanlon, Terrance P.;Rider, Lisa G.
Objective.目的明确II类主要组织相容性复合体（MHC）等位基因和肽结合基序作为青少年皮肌炎（DM）危险或保护因素的相对重要性（RI），并与成人DM中HLA相关性进行比较。方法.对142例白人青少年糖尿病患者进行DRB 1和DQA 1分型，并与193例成人糖尿病患者和797例种族匹配对照的HLA分型数据进行比较。采用随机森林分类法和多元Logistic回归分析评估HLA相关性的RI。结果HLA-DRB 1 *0301等位基因是青少年DM的主要危险因素（比值比[OR] 3.9），而DQA 1 *0301（OR 2.8）、DQA 1 *0501（OR 2.1）和DQA 1 *0501纯合性（OR 3.2）是青少年DM的额外危险因素。这些危险因素在没有明确自身抗体的成人DM患者中不存在。DQA 1等位基因 *0201（OR 0.37）、*0101（OR 0.38）和 *0102（OR 0.51）被确定为青少年DM的新的保护因子，后2个也是成年DM的保护因子。肽结合基序DRB 1（EYSTS 13）-E-9是一个风险因素，DQA 1基序F-25、S-26和（45）（V/A）W（R/K）（47）具有保护作用。随机森林分类分析显示，在已确定的青少年DM的危险因素中，DRB 1 *0301具有比DQA 1 *0301（RI 57%）、DQA 1 *0501（RI 42%）或肽结合基序更高的RI（100%）。在Logistic回归模型中，DRB 1 *0301和DQA 1 *0201分别是青少年糖尿病的最强危险因素和保护因素。结论DRB 1 *0301在RI中的排名高于DQA 1 *0501作为青少年DM的危险因素。DQA 1 *0301是一个新发现的青少年DM的HLA危险因子，而研究的3个DQA 1等位基因是新发现的青少年DM的保护因子。
Objective. To define the relative importance (RI) of class II major histocompatibility complex (MHC) alleles and peptide binding motifs as risk or protective factors for juvenile dermatomyositis (DM), and to compare these with HLA associations in adult DM. Methods. DRB1 and DQA1 typing was performed in 142 Caucasian patients with juvenile DM, and the results were compared with HLA typing data from 193 patients with adult DM and 797 race-matched controls. Random Forests classification and multiple logistic regression were used to assess the RI of the HLA associations. Results. The HLA-DRB1*0301 allele was a primary risk factor (odds ratio [OR] 3.9), while DQA1*0301 (OR 2.8), DQA1*0501 (OR 2.1), and homozygosity for DQA1*0501 (OR 3.2) were additional risk factors for juvenile DM. These risk factors were not present in patients with adult DM without defined autoantibodies. DQA1 alleles *0201 (OR 0.37), *0101 (OR 0.38), and *0102 (OR 0.51) were identified as novel protective factors for juvenile DM, the latter 2 also being protective factors in adult DM. The peptide binding motif DRB1 (EYSTS13)-E-9 was a risk factor, and DQA1 motifs F-25, S-26, and (45)(V/A)W(R/K)(47) were protective. Random Forests classification analysis revealed that among the identified risk factors for juvenile DM, DRB1*0301 had a higher RI (100%) than DQA1*0301 (RI 57%), DQA1*0501 (RI 42%), or the peptide binding motifs. In a logistic regression model, DRB1*0301 and DQA1*0201 were the strongest risk and protective factors, respectively, for juvenile DM. Conclusion. DRB1*0301 is ranked higher in RI than DQA1*0501 as a risk factor for juvenile DM. DQA1*0301 is a newly identified HLA risk factor for juvenile DM, while 3 of the DQA1 alleles studied are newly identified protective factors for juvenile DM.