Arthritogenic anti-type II collagen antibodies are pathogenic for cartilage-derived chondrocytes independent of inflammatory cells

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Amirahmadi, S. F.Monash University, Clayton, Victoria, Australia (author)

Arthritogenic anti-type II collagen antibodies are pathogenic for cartilage-derived chondrocytes independent of inflammatory cells

Article/chapterEnglish2005

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2005
Wiley,2005
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LIBRIS-ID:oai:DiVA.org:hh-48818
https://urn.kb.se/resolve?urn=urn:nbn:se:hh:diva-48818URI
https://doi.org/10.1002/art.21097DOI
https://lup.lub.lu.se/record/237603URI

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Language:English
Summary in:English

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SwePubSwePub

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Subject category:ref swepub-contenttype
Subject category:art swepub-publicationtype

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OBJECTIVE: Some monoclonal antibodies (mAb) to type II collagen (CII) are arthritogenic upon passive transfer to mice. We undertook this study to investigate whether such mAb are pathogenic in the absence of mediators of inflammation. METHODS: The arthritogenic mAb CIIC1 and M2139, and the nonarthritogenic mAb CIIF4, each reactive with a distinct and well-defined conformational epitope on CII, were compared with control mAb GAD6. Bovine chondrocytes were cultured with one of the mAb, and on days 3, 6, and 9, antibody binding by chondrocytes and newly synthesized extracellular matrix (ECM) was examined by immunofluorescence, morphologic effects were studied by electron microscopy, and synthesis of matrix components was determined by metabolic labeling with (3)H-proline for collagen and (35)S-sulfate for proteoglycans. RESULTS: All 3 mAb to CII bound to the matrix. CIIC1 and M2139 adversely affected the cultures, whereas CIIF4 did not. CIIC1 caused disorganization of CII fibrils in the ECM without affecting chondrocyte morphology, and increased matrix synthesis. M2139 caused thickening and aggregation of CII fibrils in the ECM and abnormal chondrocyte morphology but matrix synthesis was unaffected. CONCLUSION: The unique arthritogenic capacity of particular anti-CII mAb upon passive transfer could be explained by their adverse, albeit differing, effects in primary cultures of chondrocytes. Such effects occur independent of inflammation mediators and are related to the epitope specificity of the mAb. Interference with the structural integrity of CII could precede, and even initiate, the inflammatory expression of disease.

Subject headings and genre

MEDICIN OCH HÄLSOVETENSKAP Klinisk medicin Reumatologi och inflammation hsv//swe
MEDICAL AND HEALTH SCIENCES Clinical Medicine Rheumatology and Autoimmunity hsv//eng
Animals
Antibodies
Monoclonal/immunology
Arthritis/*immunology
Biomarkers
Cartilage/immunology
Chondrocytes/*immunology
Collagen Type II/*immunology
Mice

Added entries (persons, corporate bodies, meetings, titles ...)

Whittingham, S.Monash University, Clayton, Victoria, Australia (author)
Crombie, D. E.Monash University, Clayton, Victoria, Australia (author)
Nandakumar, Kutty Selva,1965-Lund University, Lund, Sweden(Swepub:hh)kutnam (author)
Holmdahl, RikardLund University,Lunds universitet,Immunologi,Forskargrupper vid Lunds universitet,Immunology,Lund University Research Groups,Lund University, Lund, Sweden(Swepub:lu)infl-rho (author)
Mackay, I. R.Monash University, Clayton, Victoria, Australia (author)
van Damme, M. P.Monash University, Clayton, Victoria, Australia (author)
Rowley, M. J.Monash University, Clayton, Victoria, Australia (author)
Monash University, Clayton, Victoria, AustraliaLund University, Lund, Sweden (creator_code:org_t)

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In:Arthritis and Rheumatism: Wiley52:6, s. 1897-19060004-35911529-0131

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By the author/editor: Amirahmadi, S. F ...; Whittingham, S.; Crombie, D. E.; Nandakumar, Kutt ...; Holmdahl, Rikard; Mackay, I. R.; show more...; van Damme, M. P.; Rowley, M. J.; show less...

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MEDICAL AND HEALTH SCIENCES: MEDICAL AND HEAL ...; and Clinical Medicin ...; and Rheumatology and ...

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