Destructive effects of murine arthritogenic antibodies to type II collagen on cartilage explants in vitro

Certain monoclonal antibodies (mAbs) to type II collagen (CII) induce arthritis in vivo after passive transfer and have adverse effects on chondrocyte cultures and inhibit self assembly of collagen fibrils in vitro. We have examined whether such mAbs have detrimental effects on pre-existing cartilag...

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Published in:	Arthritis research & therapy Vol. 7; no. 5; pp. R927 - R937
Main Authors:	Crombie, Duncan E, Turer, Muhammed, Zuasti, Beltzane Biurrun, Wood, Bayden, McNaughton, Don, Nandakumar, Kutty Selva, Holmdahl, Rikard, Van Damme, Marie-Paule, Rowley, Merrill J
Format:	Journal Article
Language:	English
Published:	England BioMed Central Ltd 01-01-2005 BioMed Central
Subjects:	Animals Antibodies Antibodies, Monoclonal - immunology Antigen-Antibody Reactions Arthritis Arthritis, Experimental - immunology Articular/immunology Autoantibodies - immunology Cartilage Cartilage, Articular - immunology Cattle Clinical Medicine Collagen Type II - immunology Coloring Agents - analysis Epitopes - immunology Experimental/immunology Extracellular Matrix - immunology Extracellular Matrix - ultrastructure Extracellular Matrix/immunology/ultrastructure Fourier Transform Infrared Immunoglobulin Fab Fragments - immunology Immunoglobulin Fc Fragments - immunology Klinisk medicin Medical and Health Sciences Medicin och hälsovetenskap Mice Monoclonal/immunology Organ Culture Techniques Protein Denaturation Proteoglycans - metabolism Reumatologi och inflammation Rheumatology and Autoimmunity Spectroscopy Spectroscopy, Fourier Transform Infrared Tolonium Chloride - analysis
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Summary:	Certain monoclonal antibodies (mAbs) to type II collagen (CII) induce arthritis in vivo after passive transfer and have adverse effects on chondrocyte cultures and inhibit self assembly of collagen fibrils in vitro. We have examined whether such mAbs have detrimental effects on pre-existing cartilage. Bovine cartilage explants were cultured over 21 days in the presence of two arthritogenic mAbs to CII (CIIC1 or M2139), a non-arthritogenic mAb to CII (CIIF4) or a control mAb (GAD6). Penetration of cartilage by mAb was determined by immunofluorescence on frozen sections and correlated with changes to the extracellular matrix and chondrocytes by morphometric analysis of sections stained with toluidine blue. The effects of mAbs on matrix components were examined by Fourier transform infrared microspectroscopy (FTIRM). A possible role of Fc-binding was investigated using F(ab)2 from CIIC1. All three mAbs to CII penetrated the cartilage explants and CIIC1 and M2139, but not CIIF4, had adverse effects that included proteoglycan loss correlating with mAb penetration, the later development in cultures of an abnormal superficial cellular layer, and an increased proportion of empty chondrons. FTIRM showed depletion and denaturation of CII at the explant surface in the presence of CIIC1 or M2139, which paralleled proteoglycan loss. The effects of F(ab)2 were greater than those of intact CIIC1. Our results indicate that mAbs to CII can adversely affect preformed cartilage, and that the specific epitope on CII recognised by the mAb determines both arthritogenicity in vivo and adverse effects in vitro. We conclude that antibodies to CII can have pathogenic effects that are independent of inflammatory mediators or Fc-binding.
Bibliography:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23
ISSN:	1478-6354 1478-6362 1478-6362 1478-6354
DOI:	10.1186/ar1766