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源自类风湿性滑膜细胞的人单克隆IgM类风湿因子特异性和亲和力的同种异型依赖性

Allotypic dependency of the specificity and avidity of human monoclonal IgM rheumatoid factors derived from rheumatoid synovial cells.

作者信息

Robbins D L, Kenny T P, Snyder L L, Ermel R W, Larrick J W

机构信息

Department of Internal Medicine, School of Medicine, University of California, Davis 95616.

出版信息

Arthritis Rheum. 1993 Mar;36(3):389-93. doi: 10.1002/art.1780360315.

Abstract

OBJECTIVE

To better understand the genetic derivation and pathogenicity of rheumatoid factor (RF) molecules in rheumatoid arthritis (RA), we have focused our studies on rheumatoid synovial cells (RSC).

METHODS

Five monoclonal human IgM rheumatoid factor (mRF)-secreting hybridomas were produced from the RSC of an RA patient. Fine subclass specificities and avidities of these RSC mRFs were compared with several paraprotein monoclonal IgM RFs using direct binding (reactivity) and competitive inhibition (specificity and avidity) enzyme-linked immunosorbent assays.

RESULTS

The following observations were made: 1) RSC mRF had greater avidity for IgG than did paraprotein mRF; 2) 4 of the 5 RSC RF were highly avid for IgG3; and, 3) the avidity of RSC RF binding for IgG3 was highest for IgG molecules expressing the G3m(5) allotype.

CONCLUSION

We conclude that RSC RF have different specificities and avidities than do paraprotein RF. This may suggest an antigen-driven process in RA synovium, with the production of higher-avidity IgG3m(5)-specific RSC RF, which could have special pathogenetic importance.

摘要

目的

为了更好地理解类风湿关节炎(RA)中类风湿因子(RF)分子的遗传起源和致病性,我们将研究重点放在了类风湿滑膜细胞(RSC)上。

方法

从一名RA患者的RSC中制备了5株分泌单克隆人IgM类风湿因子(mRF)的杂交瘤。使用直接结合(反应性)和竞争性抑制(特异性和亲和力)酶联免疫吸附测定法,将这些RSC mRF的精细亚类特异性和亲和力与几种副蛋白单克隆IgM RF进行了比较。

结果

得到了以下观察结果:1)RSC mRF对IgG的亲和力高于副蛋白mRF;2)5个RSC RF中有4个对IgG3具有高亲和力;3)对于表达G3m(5)同种异型的IgG分子,RSC RF与IgG3结合的亲和力最高。

结论

我们得出结论,RSC RF与副蛋白RF具有不同的特异性和亲和力。这可能提示RA滑膜中存在抗原驱动过程,产生了高亲和力的IgG3m(5)特异性RSC RF,这可能具有特殊的致病重要性。

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