Epitopes of Proteoglycans Eliciting an Anti-Proteoglycan Response in Chronic Immune Synovitis

• Published in: Proceedings of the National Academy of Sciences - PNAS Vol. 84; no. 3; pp. 832 - 836
• Main Authors: Yoo, Jung U., Kresina, Thomas F., Malemud, Charles J., Goldberg, Victor M.
• Format: Journal Article
• Language: English
• Published: Washington, DC National Academy of Sciences of the United States of America 01.02.1987; National Acad Sciences
• Subjects: Animals; Antibodies; Autoantibodies - analysis; Autoimmune Diseases - immunology; Autoimmune Diseases - pathology; Autoimmunity (experimental aspects and models); Biological and medical sciences; Cartilage; Chronic Disease; Disease Models, Animal; Epitopes; Epitopes - analysis; Fundamental and applied biological sciences. Psychology; Fundamental immunology; Immunoglobulin G; Mice; Molecules; Monomers; Pathology; Peptide Fragments - immunology; Proteoglycans; Proteoglycans - immunology; Rabbits; Radioimmunoassay; Sulfates; Synovitis; Synovitis - immunology; Synovitis - pathology; Human; Proteoglycan; Animal model; Synovitis; Antibody; Induction; IgG; Rabbit; Autoimmune disease; Identification; Lagomorpha; Vertebrata; Mammalia; Rheumatoid arthritis; Arthropathy
• ISSN: 0027-8424; 1091-6490
• DOI: 10.1073/pnas.84.3.832

This study details the immune response to cartilage proteoglycan in experimental chronic IgG-induced immune synovitis. Antibodies reactive with purified rabbit proteoglycan monomer were observed in nine of nine rabbits with immune synovitis. IgG-immunized but nonsynovitic control animals with no pathology showed no antibody response. A panel of murine monoclonal antibodies with defined specificity towards rabbit proteoglycan were utilized to characterize the epitope specificity of the immune synovitis polyclonal anti-proteoglycan response. One murine monoclonal antibody, 6C11, inhibited the binding of the polyclonal antisera to proteoglycan in all nine animals with significant (>40%) inhibition in six of nine rabbits. Further inhibition studies utilizing DEAE-cellulose-resolved proteoglycan tryptic peptides revealed that peptides poor in chondroitin sulfate were strong inhibitors of binding of the polyclonal antibodies to the proteoglycan substrate. In particular, keratan sulfate-containing tryptic peptides were most inhibitory on a per weight basis. These results indicate that, in chronic IgG-induced immune synovitis, anti-proteoglycan antibodies elicited are heterogeneous with regard to specificity, but a relatively large proportion predominantly recognized a portion of the proteoglycan molecule containing core protein and associated keratan sulfate.