Type II collagen-specific antibodies induce cartilage damage in mice independent of inflammation

Autor: Senga Whittingham, Merrill J. Rowley, Kutty Selva Nandakumar, Rikard Holmdahl, Allyson M. Croxford, Donald McNaughton
Jazyk: angličtina
Rok vydání: 2013
Předmět:
Cartilage
Articular
Pathology
medicine.medical_specialty
medicine.drug_class
Immunology
Type II collagen
Arthritis
Inflammation
Monoclonal antibody
Chondrocyte
Arthritis
Rheumatoid
Epitopes
Mice
Mice
Congenic
03 medical and health sciences
Chondrocytes
0302 clinical medicine
Species Specificity
Rheumatology
Antibody Specificity
Spectroscopy
Fourier Transform Infrared
medicine
Animals
Humans
Immunology and Allergy
Pharmacology (medical)
Collagen Type II
Autoantibodies
030304 developmental biology
Mice
Knockout
030203 arthritis & rheumatology
0303 health sciences
Hybridomas
business.industry
Cartilage
Autoantibody
Antibodies
Monoclonal
medicine.disease
Arthritis
Experimental
3. Good health
Disease Models
Animal
medicine.anatomical_structure
Rheumatoid arthritis
Proteoglycans
medicine.symptom
business
Zdroj: Arthritis & Rheumatism; Vol 65
Arthritis & Rheumatism
ISSN: 0004-3591
DOI: 10.1002/art.37805
Popis: Objective Murine collagen antibody–induced arthritis (CAIA), like collagen-induced arthritis, has clinical and immunopathologic features that parallel those in human rheumatoid arthritis (RA). This study was undertaken to examine the effects of autoantibodies to type II collagen (CII) on articular cartilage in the paws of mice, under conditions in which other factors that may influence joint pathology could be excluded. Methods Mice of 2 different strains, B10.QC5δ and the parental strain B10.Q, were injected intravenously with either saline or arthritogenic monoclonal antibodies (mAb) to CII. B10.QC5δ mice lack complement factor C5 and do not develop CAIA when injected with arthritogenic mAb, whereas B10.Q mice have C5 and develop CAIA when administered the mAb and a subsequent injection of lipopolysaccharide. Three days after injection the paws of the mice were examined by standard histologic methods to assess morphologic appearance and proteoglycan loss, and by synchrotron-enhanced Fourier transform infrared microspectroscopy to assess chemical evidence of structural change. Results No macroscopic or microscopic signs of inflammation were evident in the mice. However, in contrast to the saline-injected controls, all mAb-injected mice exhibited cartilage damage in all joints, with loss of proteoglycans and collagen, chondrocyte hyperplasia and/or loss, and surface damage in the interphalangeal joints. Conclusion The implication of these findings is that an autoimmune response to CII can disrupt articular cartilage, particularly that of the small joints, and the subsequent integrity of the cartilage depends on a balance between breakdown and repair. This has relevance with regard to RA, in which such autoantibodies occur but the inflammatory response may dominate clinically and mask underlying features of the autoimmune response.
Databáze: OpenAIRE
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