Arthritogenic antibodies specific for a major type II collagen triple-helical epitope bind and destabilize cartilage independent of inflammationShow others and affiliations
2008 (English)In: Arthritis & Rheumatology, ISSN 2326-5191, E-ISSN 2326-5205, Vol. 58, no 1, p. 184-196Article in journal (Refereed) Published
Abstract [en]
OBJECTIVE: To investigate the significance and pathogenic potential of a highly conserved major type II collagen triple-helical epitope-specific antibody (U1; amino acids 494-504) in vivo and in vitro in patients with early rheumatoid arthritis (RA) and in experimental animal models of collagen-induced arthritis (CIA). METHODS: U1-specific antibodies in sera from patients with early RA (with or without joint erosions) were analyzed. Disease progression in the CIA models in mice and rats with anti-U1 antibodies was compared. The pathogenicity of binding of monoclonal antibodies (mAb) UL1 and CIIF4 to the U1 epitope and the F4 epitope (aa 926-936), respectively, was compared in vivo and on chondrocyte cultures and preformed cartilage in vitro, using Fourier transform infrared microspectroscopy analysis. In addition, UL1-induced proteoglycan depletion in vivo in the presence and absence of the complement factor C5 was analyzed. RESULTS: Increased levels of U1 antibodies were observed in patients with early RA, especially in association with joint erosions. A significant correlation of U1-specific antibodies with disease progression was found in rats and mice with CIA. UL1 mAb induced, whereas CIIF4 mAb inhibited, the progression of arthritis. Similarly, UL1, but not CIIF4, impaired matrix synthesis on chondrocyte cultures and adversely affected preformed cartilage. Furthermore, UL1 induced significant proteoglycan depletion in vivo 3 days after injection, even in the absence of C5. CONCLUSION: Antibody epitope specificity contributes significantly to the development of arthritis, and the early pathogenic events operate independent of inflammation both in vitro and in vivo.
Place, publisher, year, edition, pages
2008. Vol. 58, no 1, p. 184-196
Keywords [en]
Aged, Animals, Antibodies, Monoclonal/immunology, Antibody Specificity, Arthritis, Experimental/*immunology/pathology, Arthritis, Rheumatoid/*immunology/pathology, Autoantibodies/blood/*immunology, Cartilage/*immunology/pathology, Cell Line, Tumor, Chondrosarcoma, Collagen Type II/chemistry/*immunology, Complement C5/immunology, Epitopes/immunology, Extracellular Matrix/immunology/pathology, Female, Humans, Immunoglobulin G/blood/immunology, Male, Mice, Mice, Inbred BALB C, Middle Aged, Protein Structure, Tertiary, Rats, Rats, Inbred Strains
National Category
Rheumatology and Autoimmunity
Identifiers
URN: urn:nbn:se:hh:diva-48843DOI: 10.1002/art.23049PubMedID: 18163493OAI: oai:DiVA.org:hh-48843DiVA, id: diva2:1719031
2022-12-142022-12-142023-02-21Bibliographically approved