Surface-bound anti-type II collagen-containing immune complexes induce production of tumor necrosis factor α, interleukin-1β, and interleukin-8 from peripheral blood mononuclear cells via FcγRIIa: A potential pathophysiologic mechanism for humoral anti-type II collagen immunity in arthritis
2006 (English)In: Arthritis and Rheumatism, ISSN 0004-3591, E-ISSN 1529-0131, Vol. 54, no 6, 1759-1771 p.Article in journal (Refereed) Published
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 cytokines induced in a solid-phase IC model. Monocytes were either depleted or enriched to define responder cells. Antibodies blocking Fc gamma receptors (Fc gammaR) 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 (TNFalpha), interleukin-1beta (IL-1beta), and IL-8. We found a close correlation between enzyme-linked immunosorbent assay optical density values and induction of TNFalpha (r = 0.862, P < 0.0001), IL-1beta (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 TNFalpha, IL-1beta, and IL-8 after blocking Fc gammaRIIa, but not after blocking Fc gammaRIII. 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 gammaRIIa and suppression of synovial macrophages are conceivable treatment options in such patients.
Place, publisher, year, edition, pages
2006. Vol. 54, no 6, 1759-1771 p.
Adult, Aged, Aged; 80 and over, Antigen-Antibody Complex/*immunology, Antigens; CD/*physiology, Arthritis/*immunology, Collagen Type II/*immunology, Enzyme-Linked Immunosorbent Assay, Female, Humans, Interleukin-1/*biosynthesis, Interleukin-8/*biosynthesis, Male, Middle Aged, Monocytes/immunology/*metabolism, Receptors; IgG/*physiology, Research Support; Non-U.S. Gov't, Tumor Necrosis Factor-alpha/*biosynthesis
Medical and Health Sciences
IdentifiersURN: urn:nbn:se:uu:diva-95382DOI: 10.1002/art.21892PubMedID: 16736518OAI: oai:DiVA.org:uu-95382DiVA: diva2:169567