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

Objective. To determine whether patients with osteoarthritis (OA) express cellular immunity to cartilage link protein (LP) and the G1 globular domain of proteoglycan (PG) aggrecan, and whether immunity to the G1 domain is influenced by the removal of keratan sulfate (KS). Methods. LP and the G1 globular domain of PG were isolated from human and/or bovine cartilage and used in proliferation assays with peripheral blood lymphocytes (PBL) from 42 patients with OA and 40 healthy control subjects. Results. Patients with OA expressed a higher prevalence of cellular immunity to human cartilage LP (42.4%) compared with the control group (13.3%). The prevalence of immune reactivity to bovine LP in patients with OA was lower (35.7%) compared with the immunity to human LP, but remained similar in the control group (13.8%). PBL from patients with OA exhibited low reactivity to the native G1 domain of bovine PG. However, removal of KS chains from the G1 globular domain resulted in increased cellular immune responses to the G1 domain in OA patients (45.8%) compared with the control group (7.7%). Conclusion. These results indicate the presence of immunity to cartilage-derived LP and the G1 globular domain of PG aggrecan in patients with OA and the inhibitory effect of KS chains on the G1 domain on the expression of this immunity in OA patients. This immune reactivity is commonly observed in patients with inflammatory joint disease and can experimentally induce arthritis. Thus, it may be involved in the pathogenesis of OA.