Gonzalez-Gronow M, Enghild J J, Pizzo S V
Department of Pathology, Duke University Medical Center Durham, NC 27710.
Biochim Biophys Acta. 1993 Jan 22;1180(3):283-8. doi: 10.1016/0925-4439(93)90051-2.
Rheumatoid arthritis is a disease characterized by a destructive inflammatory process in joints. Fibronectin (FN) is present at a high concentration in rheumatoid synovial tissue and it is a chemoattractant for inflammatory cells. FN fragments also play significant and specific roles in promoting inflammation. In the present study, we demonstrate that FN and the streptococcal plasminogen activator streptokinase (SK) share a common epitope which is recognized by both a rabbit anti-SK IgG and a human anti-SK IgG isolated from the serum of a rheumatoid arthritis patient. This cross-reactive antibody was present in the plasma of 40 patients with rheumatoid arthritis. The region of homology is present in a 90-kDa FN fragment generated by plasmin (Pm) digestion of FN. Amino terminal sequence analysis of this fragment demonstrates that it contains the cell binding domain of FN and the domain responsible for plasminogen binding. The epitope common to SK and FN is not reactive in native FN and it is exposed as a consequence of Pm digestion. It is, however, exposed in native SK. Examination of the sequences of FN and SK indicates a region of homology containing the sequence LTSRPA. This sequence, moreover, is present in the 90-kDa FN fragment generated by Pm digestion. The sequence is present in the amino terminal domain of SK which is essential for its ability to serve as a plasminogen activator. LTSPRA coupled to a carrier protein also reacts with anti-SK antibodies obtained from rabbit or the plasma of patients with rheumatoid arthritis. These studies suggest that the Pm-generated FN 90-kDa fragment may react with circulating antibodies originally elicited by streptococcal infections. These immune complexes may play a role in the etiology of rheumatoid arthritis.
类风湿性关节炎是一种以关节破坏性炎症过程为特征的疾病。纤连蛋白（FN）在类风湿性滑膜组织中高浓度存在，并且是炎症细胞的趋化因子。FN片段在促进炎症方面也发挥着重要且特定的作用。在本研究中，我们证明FN与链球菌纤溶酶原激活剂链激酶（SK）共享一个共同表位，该表位可被从类风湿性关节炎患者血清中分离出的兔抗SK IgG和人抗SK IgG识别。这种交叉反应性抗体存在于40例类风湿性关节炎患者的血浆中。同源区域存在于通过纤溶酶（Pm）消化FN产生的90-kDa FN片段中。对该片段的氨基末端序列分析表明，它包含FN的细胞结合结构域和负责纤溶酶原结合的结构域。SK和FN共有的表位在天然FN中无反应性，并且由于Pm消化而暴露。然而，它在天然SK中是暴露的。对FN和SK序列的检查表明存在一个包含LTSRPA序列的同源区域。此外，该序列存在于通过Pm消化产生的90-kDa FN片段中。该序列存在于SK的氨基末端结构域中，这对其作为纤溶酶原激活剂的能力至关重要。与载体蛋白偶联的LTSPRA也与从兔或类风湿性关节炎患者血浆中获得的抗SK抗体发生反应。这些研究表明，Pm产生的FN 90-kDa片段可能与最初由链球菌感染引发的循环抗体发生反应。这些免疫复合物可能在类风湿性关节炎的病因学中起作用。
