Arthritogenic antibodies specific for a major type II collagen triple-helical epitope bind and destabilize cartilage independent of inflammation

Kutty Selva Nandakumar, Estelle Bajtner, Leigh Raymond Hill, Beate Bohm, Merrill Joy Rowley, Harald Burkhardt, Rikard Holmdahl

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40 Citations (Scopus)

Abstract

Objective: To investigate the significance and pathogenic potential of a highly conserved major triple helical collagen type II epitope (U1; aa 494-504) specific antibodies in vivo and in vitro. Methods: U1-specific antibodies in early RA (with or without joint erosions) sera were analyzed. Disease progression in mouse and rat CIA with anti-U1 antibodies was compared. Pathogenicity of mAbs (UL1 and CIIF4) binding to U1 and F4 (aa 926-936) epitopes was compared in vivo, and in vitro on chondrocyte cultures and preformed cartilage (FTIRM analysis). UL1 induced proteoglycan depletion in vivo in the presence and absence of complement factor 5 (C5) was analyzed. Results: Increased levels of U1 antibodies are observed in early RA especially in association with joint erosions. A significant correlation of U1-specific antibodies with disease progression was found in experimental arthritis. UL1 induced, whereas CIIF4 inhibited 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 the injection, even in the absence of C5. Conclusions: Antibody epitope specificity contributes significantly for the development of arthritis and the early pathogenic events operate independent of inflammation both in vitro and in vivo.
Original languageEnglish
Pages (from-to)184 - 196
Number of pages12
JournalArthritis & Rheumatism
Volume58
Publication statusPublished - 2008

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