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针对剪接体的自身免疫反应。类风湿性关节炎、混合性结缔组织病和系统性红斑狼疮之间的免疫学联系。

Autoimmune response to the spliceosome. An immunologic link between rheumatoid arthritis, mixed connective tissue disease, and systemic lupus erythematosus.

作者信息

Hassfeld W, Steiner G, Studnicka-Benke A, Skriner K, Graninger W, Fischer I, Smolen J S

机构信息

Lainz Hospital, Vienna, Austria.

出版信息

Arthritis Rheum. 1995 Jun;38(6):777-85. doi: 10.1002/art.1780380610.

DOI:10.1002/art.1780380610
PMID:7779120
Abstract

OBJECTIVE

To assess the significance of autoantibodies to RA33, the A2 protein of the heterogeneous nuclear ribonucleoproteins (hnRNP), and to the related hnRNP proteins A1, B1, and B2 in rheumatic diseases.

METHODS

Using a partially purified preparation of hnRNP-A and hnRNP-B proteins, sera from 303 patients with various rheumatic diseases were investigated by immunoblotting. For the analysis of cross-reactivities, autoantibodies were affinity purified by blot elution.

RESULTS

Anti-A2/RA33 was found in 35% of rheumatoid arthritis (RA) patients, 38% of mixed connective tissue disease (MCTD) patients, 23% of systemic lupus erythematosus (SLE) patients, and, apart from single exceptions, not in patients with other rheumatic diseases. All anti-A2/RA33-positive sera were also reactive with B1 and B2, and anti-A2/RA33 antibodies cross-reacted with both proteins. Antibodies to hnRNP-A1 were found less frequently; moreover, the majority of anti-A1-positive sera also contained anti-A2/RA33 antibodies. In anti-A1, anti-A2/RA33 double-positive sera, cross-reactivity between the 2 antibodies was generally observed. In SLE patients, the presence of anti-A2/RA33 was correlated with the presence of anti-(U1) small nuclear RNP (snRNP) and anti-Sm (P < 0.0001 and P < 0.005, respectively), but there was no evidence for cross-reactivity between antibodies to hnRNP and antibodies to snRNP antigens.

CONCLUSION

Since both hnRNPs and snRNPs are essential components of the spliceosome, the data show that the immune systems of patients with RA, SLE, and MCTD react to this functional complex. However, compared with MCTD and SLE patients, RA patients have a more restricted immune response to the spliceosome: they react to hnRNP proteins, particularly to hnRNP-A2/RA33, but not to snRNPs.

摘要

目的

评估抗RA33自身抗体、异质性核糖核蛋白(hnRNP)的A2蛋白以及相关hnRNP蛋白A1、B1和B2在风湿性疾病中的意义。

方法

使用部分纯化的hnRNP - A和hnRNP - B蛋白制剂,通过免疫印迹法检测303例各种风湿性疾病患者的血清。为分析交叉反应性,通过印迹洗脱法亲和纯化自身抗体。

结果

在35%的类风湿关节炎(RA)患者、38%的混合性结缔组织病(MCTD)患者、23%的系统性红斑狼疮(SLE)患者中发现抗A2/RA33,除个别例外,其他风湿性疾病患者中未发现。所有抗A2/RA33阳性血清也与B1和B2反应,且抗A2/RA33抗体与这两种蛋白均有交叉反应。抗hnRNP - A1抗体较少见;此外,大多数抗A1阳性血清也含有抗A2/RA33抗体。在抗A1、抗A2/RA双重阳性血清中,通常观察到两种抗体之间的交叉反应。在SLE患者中,抗A2/RA33的存在与抗(U1)小核核糖核蛋白(snRNP)和抗Sm的存在相关(分别为P < 0.0001和P < 0.005),但没有证据表明hnRNP抗体与snRNP抗原抗体之间存在交叉反应。

结论

由于hnRNP和snRNP都是剪接体的重要组成部分,数据表明RA、SLE和MCTD患者的免疫系统对这种功能复合物产生反应。然而,与MCTD和SLE患者相比,RA患者对剪接体的免疫反应更具局限性:他们对hnRNP蛋白,特别是对hnRNP - A2/RA33产生反应,但对snRNP无反应。

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