title: Chemical changes demonstrated in cartilage by synchrotron infrared microspectroscopy in an antibody-induced murine model of rheumatoid arthritis.
abstract: Collagen antibody-induced arthritis develops in mice following passive transfer of monoclonal antibodies (mAbs) to type II collagen (CII) and is attributed to effects of proinflammatory immune complexes, but transferred mAbs may react directly and damagingly with CII. To determine whether such mAbs cause cartilage damage in vivo in the absence of inflammation, mice lacking complement factor 5 that do not develop joint inflammation were injected intravenously with two arthritogenic mAbs to CII, M2139 and CIIC1. Paws were collected at day 3, decalcified, paraffin embedded, and 5-μm sections were examined using standard histology and synchrotron Fourier-transform infrared microspectroscopy (FTIRM). None of the mice injected with mAb showed visual or histological evidence of inflammation but there were histological changes in the articular cartilage including loss of proteoglycan and altered chondrocyte morphology. Findings using FTIRM at high lateral resolution revealed loss of collagen and the appearance of a new peak at 1635 cm(-1) at the surface of the cartilage interpreted as cellular activation. Thus, we demonstrate the utility of synchrotron FTIRM for examining chemical changes in diseased cartilage at the microscopic level and establish that arthritogenic mAbs to CII do cause cartilage damage in vivo in the absence of inflammation.
authors: Monash University, Department of Biochemistry and Molecular Biology, Clayton, Victoria, Australia.
authors: Allyson M
authors: AM
authors: Croxford
authors: Kutty Selva
authors: KS
authors: Nandakumar
authors: Rikard
authors: R
authors: Holmdahl
authors: Mark J
authors: MJ
authors: Tobin
authors: Don
authors: D
authors: McNaughton
authors: Merrill J
authors: MJ
authors: Rowley
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal; D001169:Arthritis, Experimental / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D002356:Cartilage / Q000737:chemistry* / Q000473:pathology; D019902:Chondrocytes / Q000737:chemistry / Q000378:metabolism / Q000473:pathology; D016000:Cluster Analysis; D024043:Collagen Type II / Q000276:immunology; D003182:Complement C5 / Q000172:deficiency / Q000276:immunology; D004195:Disease Models, Animal; D033023:Foot Joints / Q000737:chemistry / Q000378:metabolism / Q000473:pathology; D006651:Histocytochemistry; D051379:Mice; D008822:Mice, Transgenic; D015591:Microspectrophotometry; D013055:Spectrophotometry, Infrared / Q000379:methods*; D017550:Spectroscopy, Fourier Transform Infrared; D017356:Synchrotrons
chemical_list: D000911:Antibodies, Monoclonal; D024043:Collagen Type II; D003182:Complement C5