Kenny T P, Leider P, Duong P A, Robbins D L
Department of Internal Medicine, School of Medicine, University of California, Davis 95616, USA.
J Rheumatol. 1996 May;23(5):819-25.
Rheumatoid factor (RF) is the predominant autoantibody in rheumatoid arthritis (RA). but its role in the pathogenesis of RA remains unclear. We hypothesized that surface RF (sRF) expressed on antigen presenting B cells (B-APC) might have different binding specificities than secreted RF.
We examined RF binding in a novel RF antigen capture enzyme linked immunoassay (ACE) that mimicked sRF binding, and compared it with a direct binding enzyme linked immunoassay (DBE) that mimicked secreted RF.
Significant differences in binding characteristics by the same rheumatoid synovial cell (RSC) derived monoclonal RF (mRF) were observed between the ACE and the DBE. For example, several mRF that demonstrated the classical Ga binding pattern (binding to IgG1, 2, and 4) in the DBE showed considerable binding to selected IgG3 proteins in the ACE; and several mRF that bound only to rabbit IgG in DBE bound to human IgG in the ACE.
These RF reactivity differences may be attributed to conformational modifications in the RF and IgG molecules that expose different epitopes or altered binding sites depending on the physical state of the antibody and/or antigen and may be important pathogenically.
类风湿因子(RF)是类风湿关节炎(RA)中主要的自身抗体,但其在RA发病机制中的作用仍不清楚。我们推测抗原呈递B细胞(B-APC)上表达的表面RF(sRF)可能具有与分泌型RF不同的结合特异性。
我们在一种模拟sRF结合的新型RF抗原捕获酶联免疫分析(ACE)中检测RF结合,并将其与模拟分泌型RF的直接结合酶联免疫分析(DBE)进行比较。
在ACE和DBE之间观察到来自同一类风湿滑膜细胞(RSC)的单克隆RF(mRF)在结合特性上存在显著差异。例如,在DBE中表现出经典的Ga结合模式(与IgG1、2和4结合)的几种mRF在ACE中显示出与选定的IgG3蛋白有相当程度的结合;在DBE中仅与兔IgG结合的几种mRF在ACE中与人IgG结合。
这些RF反应性差异可能归因于RF和IgG分子的构象修饰,根据抗体和/或抗原的物理状态暴露不同的表位或改变结合位点,并且可能在发病机制上具有重要意义。