Journal
ARTHRITIS AND RHEUMATISM
Volume 54, Issue 6, Pages 1759-1771Publisher
WILEY
DOI: 10.1002/art.21892
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Objective. Type II collagen (CII) is a major component of hyaline cartilage, and antibodies against CII are found in a subgroup of patients with rheumatoid arthritis. We undertook this study to investigate whether and how antibodies directed against CII can form solid-phase immune complexes (ICs) with cytokine-inducing properties in a model theoretically resembling the situation in the inflamed joint, in which CII is exposed for interaction with anti-CII antibodies during periods of inflammation. Methods. Sixty-five arthritis patients with varying levels of anti-native CII antibodies and 10 healthy controls were evaluated concerning anti-CII and cyto-kines induced in a solid-phase IC model. Monocytes were either depleted or enriched to define responder cells. Antibodies blocking Fc gamma receptors (Fc gamma R) were used to define the responsible T cell surface receptors. Results. ICs containing anti-CII from arthritis patients induced the production of tumor necrosis factor alpha(TNF alpha), interieukin-1 ss (IL-1 ss), and IL-8. We found a close correlation between enzyme-linked immunosorbent assay optical density values and induction of TNF alpha (r = 0.862, P < 0.0001), IL-1 ss (r = 0.839, P < 0.0001), and IL-8 (r = 0.547, P < 0.0001). The anti-CII-containing IC density threshold needed for cytokine induction differed among peripheral blood mononuclear cell donors. Anti-CII-containing IC-induced cytokine production was almost totally abolished (> 99%) after monocyte depletion, and receptor blocking studies showed significant decreases in the production of TNF alpha, IL-1 ss, and IL-8 after blocking Fc gamma RIIa, but not after blocking Fc gamma RIII. Conclusion. These findings represent a possible mechanism for perpetuation of joint inflammation in the subgroup of arthritis patients with high levels of anti-CII. Blockade of Fc gamma RIIa and suppression of synovial macrophages are conceivable treatment options in such patients.
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