Streptokinase and human fibronectin share a common epitope: implications for regulation of fibrinolysis and rheumatoid arthritis.
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.
Gonzalez-Gronow
M
M
Department of Pathology, Duke University Medical Center Durham, NC 27710.
Enghild
J J
JJ
Pizzo
S V
SV
D000595:Amino Acid Sequence; D001172:Arthritis, Rheumatoid / Q000276:immunology*; D004591:Electrophoresis, Polyacrylamide Gel; D000939:Epitopes; D005342:Fibrinolysis / Q000276:immunology*; D005353:Fibronectins / Q000276:immunology*; D006801:Humans; D008969:Molecular Sequence Data; D017386:Sequence Homology, Amino Acid; D013300:Streptokinase / Q000276:immunology*
D000939:Epitopes; D005353:Fibronectins; D013300:Streptokinase