四个患有不同形式肌炎的种族群体中主要组织相容性复合体II类等位基因与自身抗体的相互关系。

Interrelationship of major histocompatibility complex class II alleles and autoantibodies in four ethnic groups with various forms of myositis.

作者信息

Arnett F C, Targoff I N, Mimori T, Goldstein R, Warner N B, Reveille J D

机构信息

University of Texas-Houston Health Science Center, USA.

出版信息

Arthritis Rheum. 1996 Sep;39(9):1507-18. doi: 10.1002/art.1780390910.

DOI:10.1002/art.1780390910

PMID:8814062

Abstract

OBJECTIVE

To examine interrelationships among myositis subsets, autoantibodies, and major histocompatibility complex (MHC) class II alleles across ethnic lines, and to localize genetic susceptibility (presence of HLA-DR versus DQ) to myositis within the MHC class II region.

METHODS

MHC class II alleles (HLA-DRB1, DQA1, and DQB1, detected by DNA oligotyping) and myositis-specific autoantibodies (MSA) were determined in 224 patients with various myositis syndromes, including 89 whites, 89 African-Americans, 25 Mexican-Americans, and 21 Japanese.

RESULTS

Anti-Jo-1 (histidyl-transfer RNA [tRNA] synthetase) and other MSAs (anti-PL-12, anti-PL-7, anti-OJ, anti-EJ, anti-KJ, anti-tRNA, and anti-signal recognition particle) were equally distributed among the races, but occurred more often in patients with polymyositis (PM) than in those with dermatomyositis (DM) or other myositis syndromes. MSA frequencies were significantly positively associated with anti-Ro (SS-A) (P = 0.002), and significantly negatively associated with anti-U1 RNP (P = 0.003). Frequencies of the HLA-DRB10301 (DR3), DQA10501, and DQB10201 (DQ2) alleles (and haplotype) were each increased in white patients with myositis, especially those with PM, but most strikingly in those with MSAs. However, in the other ethnic groups, except the Japanese group, only frequencies of HLA-DQA10501 and the structurally similar DQA10401 alleles were significantly increased. The presence of HLA-DQA10501 or 0401 was most significantly associated with anti-Jo-1, anti-PL-12, and other MSAs, compared with myositis patients without MSAs (P = 0.0008, Pcorr = 0.01, odds ratio [OR] = 3.7), and with normal, ethnically matched controls (P = 3 x 10(-7), Pcorr = 1 x 10(-6), OR = 6.5). Among MSA-positive patients who were negative for HLA-DQA10501 and 0401, including Japanese patients, the HLA-DQA10102 and 0103 alleles predominated. In addition, there appeared to be a negative association of the HLA-DR2 alleles (DRB11501 and *1503) with PM (P = 0.007, Pcorr not significant, OR = 0.39), but not with DM or myositis overall.

CONCLUSION

By transracial gene mapping, genetic susceptibility to anti-Jo-1 and other MSAs in patients with myositis can be localized within the MHC region to the HLA-DQA1 locus.

摘要

目的

研究不同种族的肌炎亚型、自身抗体和主要组织相容性复合体（MHC）II类等位基因之间的相互关系，并在MHC II类区域内确定肌炎的遗传易感性（HLA - DR与DQ的存在情况）。

方法

对224例患有各种肌炎综合征的患者进行了MHC II类等位基因（通过DNA寡核苷酸分型检测的HLA - DRB1、DQA1和DQB1）和肌炎特异性自身抗体（MSA）的检测，其中包括89名白人、89名非裔美国人、25名墨西哥裔美国人以及21名日本人。

结果

抗Jo - 1（组氨酰 - 转运RNA [tRNA]合成酶）和其他MSA（抗PL - 12、抗PL - 7、抗OJ、抗EJ、抗KJ、抗tRNA和抗信号识别颗粒）在各种族中分布均匀，但在多发性肌炎（PM）患者中出现的频率高于皮肌炎（DM）或其他肌炎综合征患者。MSA频率与抗Ro（SS - A）显著正相关（P = 0.002），与抗U1 RNP显著负相关（P = 0.003）。白人肌炎患者中，尤其是PM患者，HLA - DRB10301（DR3）、DQA10501和DQB10201（DQ2）等位基因（以及单倍型）的频率均有所增加，在伴有MSA的患者中最为显著。然而，在其他种族群体中，除了日本人群体，只有HLA - DQA10501和结构相似的DQA10401等位基因的频率显著增加。与无MSA的肌炎患者相比（P = 0.0008，校正P = 0.01，优势比[OR] = 3.7），以及与种族匹配的正常对照相比（P = 3×10⁻⁷，校正P = 1×10⁻⁶，OR = 6.5），HLA - DQA10501或0401的存在与抗Jo - 1、抗PL - 12及其他MSA最为显著相关。在HLA - DQA10501和0401阴性的MSA阳性患者中，包括日本患者，HLA - DQA10102和0103等位基因占主导。此外，HLA - DR2等位基因（DRB11501和*1503）与PM似乎呈负相关（P = 0.007，校正P不显著，OR = 0.39），但与DM或总体肌炎无关。