CELLULAR-IMMUNITY TO THE G1 DOMAIN OF CARTILAGE PROTEOGLYCAN AGGRECANIS ENHANCED IN PATIENTS WITH RHEUMATOID-ARTHRITIS BUT ONLY AFTER REMOVAL OF KERATAN SULFATE

Objective. To determine whether patients with rheumatoid arthritis (RA ) express cellular immunity to the purified G1 globular domain of cart ilage proteoglycan (PG) aggrecan and whether it is influenced by the r emoval of keratan sulfate (KS) chains from the molecule. Methods. The G1 globular domain of PG was purified from mature bovine articular car tilage, digested with keratanase, and used in proliferation assays wit h peripheral blood lymphocytes (PBL) isolated from 43 patients with RA , 11 patients with nonarticular rheumatism (NAR), including soft tissu e rheumatism and mechanical back pain, and 13 healthy age- and sex-mat ched control subjects. Results. Removal of KS chains from the G1 globu lar domain resulted in significantly increased prevalence and values o f cellular immune responses to G1 in RA patients compared with the con trol and NAR groups. In the majority of RA patients, KS chains on G1 s ignificantly inhibited its immune recognition by PBL, There was no sig nificant effect of KS removal on the immunity to G1 in patients,vith N AR and in the healthy control group. Conclusion. These results reveal that immune reactivity to the G1 globular domain of the cartilage PG a ggrecan is enhanced in patients with RA but only when KS chains are re moved. Thus, KS chains inhibit immune responses to this domain of aggr ecan, Since immunity to the G1 globular domain of aggrecan induces an erosive polyarthritis in BALB/c mice after removal of KS chains, immun ity to the G1 globular domain, cleaved by proteases to remove KS chain s, may play a role in the pathogenesis of RA.