Epitopes of group A streptococcal M protein shared with antigens of articular cartilage and synovium.
Rabbit antisera evoked by purified pepsin-extracted group A streptococcal M proteins were screened for the presence of joint cross-reactive antibodies by indirect immunofluorescence using thin sections of mouse knee joints. Pep M1, M5, and M18 antisera contained antibodies that cross-reacted with chondrocytes, cartilage, and synovium. Immunofluorescence inhibition assays showed that some of the joint cross-reactive epitopes were shared among the three heterologous serotypes of M protein. The pep M5 joint cross-reactive epitopes were localized to three different synthetic peptides of the C-terminal region of pep M5. Immunoblot analyses showed that the M5 joint cross-reactive antibodies recognized two proteins of human synovium and cartilage of molecular mass 56 and 58 kDa. The cross-reactive antibodies binding to the 56-kDa protein were inhibited by purified vimentin in immunoblot inhibition experiments. M protein-specific antibodies from patients with acute rheumatic fever were also shown to cross-react with joint tissue in a pattern similar to the rabbit antisera. Rabbit and human M protein-specific antibodies that were bound to articular cartilage activated significant levels of complement when compared to control serum, suggesting that M protein joint cross-reactive antibodies could potentially be involved in the pathogenesis of ARF and arthritis.
Baird
R W
RW
Department of Veterans Affairs Medical Center, Memphis, TN 38104.
Bronze
M S
MS
Kraus
W
W
Hill
H R
HR
Veasey
L G
LG
Dale
J B
JB
D000907:Antibodies, Bacterial / Q000276:immunology*; D000942:Antigens, Bacterial / Q000276:immunology; D001172:Arthritis, Rheumatoid / Q000276:immunology*; D001425:Bacterial Outer Membrane Proteins; D001426:Bacterial Proteins / Q000276:immunology*; D015153:Blotting, Western; D002352:Carrier Proteins; D002358:Cartilage, Articular / Q000276:immunology*; D003429:Cross Reactions; D005455:Fluorescent Antibody Technique; D006801:Humans; D010455:Peptides / Q000276:immunology; D012213:Rheumatic Fever / Q000276:immunology*; D013297:Streptococcus pyogenes / Q000276:immunology*; D013583:Synovial Membrane / Q000276:immunology*
D000907:Antibodies, Bacterial; D000942:Antigens, Bacterial; D001425:Bacterial Outer Membrane Proteins; D001426:Bacterial Proteins; D002352:Carrier Proteins; D010455:Peptides; C014689:streptococcal M protein