Cellular immunity to the G1 domain of cartilage proteoglycan aggrecan is 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 cartilage proteoglycan (PG) aggrecan and whether it is influenced by the removal of keratan sulfate (KS) chains from the molecule.


METHODS
The G1 globular domain of PG was purified from mature bovine articular cartilage, digested with keratanase, and used in proliferation assays with peripheral blood lymphocytes (PBL) isolated from 43 patients with RA, 11 patients with nonarticular rheumatism (NAR), including soft tissue rheumatism and mechanical back pain, and 13 healthy age- and sex-matched control subjects.


RESULTS
Removal of KS chains from the G1 globular domain resulted in significantly increased prevalence and values of cellular immune responses to G1 in RA patients compared with the control and NAR groups. In the majority of RA patients, KS chains on G1 significantly inhibited its immune recognition by PBL. There was no significant effect of KS removal on the immunity to G1 in patients with NAR and in the healthy control group.


CONCLUSIONS
These results reveal that immune reactivity to the G1 globular domain of the cartilage PG aggrecan is enhanced in patients with RA but only when KS chains are removed. Thus, KS chains inhibit immune responses to this domain of aggrecan. Since immunity to the G1 globular domain of aggrecan induces an erosive polyarthritis in BALB/c mice after removal of KS chains, immunity to the G1 globular domain, cleaved by proteases to remove KS chains, may play a role in the pathogenesis of RA.
Guerassimov
A
A
Shriners Hospital for Children, Montreal, Quebec, Canada.
Zhang
Y
Y
Banerjee
S
S
Cartman
A
A
Leroux
J Y
JY
Rosenberg
L C
LC
Esdaile
J
J
Fitzcharles
M A
MA
Poole
A R
AR
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D053674:Aggrecans; D000818:Animals; D001172:Arthritis, Rheumatoid / Q000276:immunology* / Q000378:metabolism; D002417:Cattle; D016326:Extracellular Matrix Proteins; D005260:Female; D006801:Humans; D007111:Immunity, Cellular / Q000502:physiology*; D007632:Keratan Sulfate / Q000502:physiology*; D037181:Lectins, C-Type; D008297:Male; D008875:Middle Aged; D010446:Peptide Fragments / Q000235:genetics / Q000276:immunology*; D011509:Proteoglycans / Q000235:genetics / Q000276:immunology*; D012016:Reference Values
D053674:Aggrecans; D016326:Extracellular Matrix Proteins; D037181:Lectins, C-Type; D010446:Peptide Fragments; D011509:Proteoglycans; D007632:Keratan Sulfate