系统性红斑狼疮中抗独特型抗体与DNA的交叉反应性。

Cross-reactivity of antiidiotypic antibodies with DNA in systemic lupus erythematosus.

作者信息

Eivazova E R, McDonnell J M, Sutton B J, Staines N A

机构信息

King's College London, UK.

出版信息

Arthritis Rheum. 2000 Feb;43(2):429-39. doi: 10.1002/1529-0131(200002)43:2<429::AID-ANR25>3.0.CO;2-N.

DOI:10.1002/1529-0131(200002)43:2<429::AID-ANR25>3.0.CO;2-N

PMID:10693885

Abstract

OBJECTIVE

To assess the functional relationship between antibodies reactive with DNA and antibodies reactive with the idiotypes (idiopeptides) of anti-DNA antibodies that are associated with systemic lupus erythematosus (SLE) in mice.

METHODS

Antiidiotypic antibodies that appeared spontaneously in lupus mice, and others that were induced by immunization of normal, non-lupus mice, were analyzed for their reactivity by a range of direct binding, competition enzyme-linked immunosorbent assay (ELISA), and surface plasmon resonance (SPR) methods. Their reactions were assessed against synthetic peptides representing sequences of the V(H) region of anti-DNA monoclonal antibody (mAb) V-88, against the native mAb itself, and against mammalian DNA.

RESULTS

In lupus mice, only sera with the highest reactivity against double-stranded DNA (dsDNA) also reacted with idiopeptides in ELISA, and this showed a strong statistical correlation. However, there was no significant relationship between antiidiotypic antibodies and anti-single-stranded DNA antibodies. Immunization of (BALB/c x NZW)F1 mice with idiopeptides p64 (V(H) residues 64-80) or p92 (V(H) residues 92-105) induced antibodies that reacted not only against the respective peptides, but also against the native parent anti-DNA mAb V-88. Furthermore, the immune antiidiopeptide antibodies cross-reacted with dsDNA. Competition SPR experiments with the BIAcore system supported this observation. The binding reaction of V(H) peptide p64 (representing the CDR-H2/FR-H3 region of V-88) with antiidiopeptide antibodies was inhibited by dsDNA.

CONCLUSION

This study identified a unique set of autoantibodies in SLE. They react with both autoantibody idiotopes and with dsDNA, thus having a dual specificity for 2 autoantigens. Because these antiidiotope antibodies arise naturally during the development of lupus disease, and because they bind also to dsDNA, this provides a mechanism whereby the production of anti-dsDNA antibodies is stimulated. These idiotopes on autoantibodies in lupus act as natural mimotopes for inducing anti-dsDNA antibodies, which, due to their dual specificity, may significantly contribute to the pathology of nephritis in SLE.

摘要

目的

评估与DNA反应的抗体和与系统性红斑狼疮（SLE）小鼠中抗DNA抗体的独特型（独特肽段）反应的抗体之间的功能关系。

方法

通过一系列直接结合、竞争酶联免疫吸附测定（ELISA）和表面等离子体共振（SPR）方法，分析狼疮小鼠中自发出现的抗独特型抗体以及通过免疫正常非狼疮小鼠诱导产生的其他抗独特型抗体的反应性。针对代表抗DNA单克隆抗体（mAb）V - 88的V（H）区域序列的合成肽、天然mAb本身以及哺乳动物DNA，评估它们的反应。

结果

在狼疮小鼠中，只有对双链DNA（dsDNA）反应性最高的血清在ELISA中也与独特肽段反应，且显示出很强的统计学相关性。然而，抗独特型抗体与抗单链DNA抗体之间没有显著关系。用独特肽段p64（V（H）残基64 - 80）或p92（V（H）残基92 - 105）免疫（BALB/c×NZW）F1小鼠诱导产生的抗体不仅与各自的肽段反应，还与天然亲本抗DNA mAb V - 88反应。此外，免疫抗独特型肽抗体与dsDNA发生交叉反应。使用BIAcore系统进行的竞争SPR实验支持了这一观察结果。V（H）肽p64（代表V - 88的CDR - H2/FR - H3区域）与抗独特型肽抗体的结合反应受到dsDNA的抑制。

结论

本研究在SLE中鉴定出一组独特的自身抗体。它们与自身抗体独特型和dsDNA都发生反应，因此对两种自身抗原具有双重特异性。由于这些抗独特型抗体在狼疮疾病发展过程中自然产生，并且它们也与dsDNA结合，这提供了一种刺激抗dsDNA抗体产生的机制。狼疮中自身抗体上的这些独特型作为诱导抗dsDNA抗体的天然模拟表位，由于其双重特异性，可能对SLE肾炎的病理过程有显著贡献。