Presence of antibodies to native G1 domain of aggrecan core protein in synovial fluids from patients with various joint diseases

Abstract

Objective. To investigate the occurrence of IgG antibodies to aggrecan in synovial fluids (SF) from patients with arthritis and various articular diseases, and to determine the nature of epitopes present within aggrecan that react with these antibodies. Methods. SF samples were reacted with native aggrecan, reduced and alkylated aggrecan, chondroitin sulfate, and keratan sulfate, using dot‐blots and a novel enzyme‐linked immunosorbent assay (ELISA). The nature of the epitopes present on aggrecan was elucidated using Western blots and a competitive inhibition ELISA. Results. IgG antibodies to aggrecan were found in >50% of the SF samples tested. No IgG antibody reactivity was observed in serum from the same patients. The antibodies appeared to react predominantly with native aggrecan, and there was no disease specificity. It was shown that the epitopes to these antibodies were located within the N‐terminal region of the core protein. Conclusion. This study demonstrates the frequent occurrence of IgG antibodies to aggrecan in human SF. The major epitope is located in the G1 domain of the aggrecan core protein. These IgG antibodies appear to be produced locally within the synovial cavity, probably in response to various articular diseases, resulting in the loss of native aggrecan from articular cartilage.

Cartilage proteoglycan aggrecan epitopes induce proinflammatory autoreactive T-cell responses in rheumatoid arthritis and osteoarthritis

“…Among others, such as collagens,9 human cartilage glycoprotein-39 (HC-gp39),10 link protein,11 12 human cartilage proteoglycan aggrecan (PG) might be an autoimmune target 13 14 15. Indeed, immune responses to PG and a few T-cell epitopes have been detected in patients with RA, juvenile idiopathic arthritis, osteoarthritis and ankylosing spondylitis12 13 14 16 17 18 19 20 supporting the hypothesis.…”

Immunopathogenesis of osteoarthritis

“…Anti-CCP antibodies were detected in 7 out of 136 OA patients [129], while another group also detected them in OA patients but at significantly lower levels compared to RA patients [130]. Antibodies against native G1 domain of aggrecan core protein were found in synovial fluid of OA patients [131]. Using proteomic approach, Xiang et al identified triosephosphate isomerase (TPI) as an important antigen with autoantibodies present specifically in OA but not in RA [127].…”

Immune responses to cartilage link protein and the G1 domain of proteoglycan aggrecan in patients with osteoarthritis

“…Cell-mediated immune reactivity to cartilage PG was shown in patients with OA (21). The frequent occurrence of IgG antibodies to the native G1 domain of PG was found in the synovial fluid of OA patients (22). Recently, we demonstrated the presence of cellular immune reactions to LP and the G1 domain in patients with different inflammatory arthritides (23)(24)(25)(26).…”