Antibodies to Cartilage Oligomeric Matrix Protein Are Pathogenic in Mice and May Be Clinically Relevant in Rheumatoid Arthritis

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Antibodies to Cartilage Oligomeric Matrix Protein Are Pathogenic in Mice and May Be Clinically Relevant in Rheumatoid Arthritis

Ge, C. R. (author): Karolinska Institutet,Karolinska Inst, Sweden

Dobritzsch, Doreen, 1972- (author): Uppsala universitet,Biokemi,Uppsala Univ, Sweden

Lonnblom, E. (author): Karolinska Institutet,Karolinska Inst, Sweden

Liang, B. B. (author): Karolinska Inst, Stockholm, Sweden.;Southern Med Univ, Guangzhou, Peoples R China.

Cai, W. W. (author): Karolinska Inst, Stockholm, Sweden.

Fahlquist-Hagert, C. (author): Karolinska Inst, Stockholm, Sweden.;Univ Turku, Turku, Finland.

Li, T. T. (author): Karolinska Inst, Stockholm, Sweden.

Kastbom, Alf (author): Linköpings universitet,Avdelningen för inflammation och infektion,Medicinska fakulteten,Region Östergötland, Reumatologiska kliniken i Östergötland

Gjertsson, Inger, 1962 (author): Gothenburg University,Göteborgs universitet,Institutionen för medicin, avdelningen för reumatologi och inflammationsforskning,Institute of Medicine, Department of Rheumatology and Inflammation Research,Univ Gothenburg, Gothenburg, Sweden.

Dobritzsch, D. (author)

Holmdahl, R. (author): Karolinska Institutet,Karolinska Inst, Sweden; Southern Med Univ, Peoples R China

Tong, Dongmei (author): Karolinska Inst, Sweden

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2022-04-27
2022
English.
In: Arthritis & Rheumatology. - : Wiley. - 2326-5191 .- 2326-5205.

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Journal article (peer-reviewed)

Abstract Subject headings

Objective Cartilage oligomeric matrix protein (COMP) is an autoantigen in rheumatoid arthritis (RA) and experimental models of arthritis. This study was undertaken to investigate the structure, function, and relevance of anti-COMP antibodies. Methods We investigated the pathogenicity of monoclonal anti-COMP antibodies in mice using passive transfer experiments, and we explored the interaction of anti-COMP antibodies with cartilage using immunohistochemical staining. The interaction of the monoclonal antibody 15A11 in complex with its specific COMP epitope P6 was determined by x-ray crystallography. An enzyme-linked immunosorbent assay and a surface plasma resonance technique were used to study the modulation of calcium ion binding to 15A11. The clinical relevance and value of serum IgG specific to the COMP P6 epitope and its citrullinated variants were evaluated in a large Swedish cohort of RA patients. Results The murine monoclonal anti-COMP antibody 15A11 induced arthritis in naive mice. The crystal structure of the 15A11-P6 complex explained how the antibody could bind to COMP, which can be modulated by calcium ions. Moreover, serum IgG specific to the COMP P6 peptide and its citrullinated variants was detectable at significantly higher levels in RA patients compared to healthy controls and correlated with a higher disease activity score. Conclusion Our findings provide the structural basis for binding a pathogenic anti-COMP antibody to cartilage. The recognized epitope can be citrullinated, and levels of antibodies to this epitope are elevated in RA patients and correlate with higher disease activity, implicating a pathogenic role of anti-COMP antibodies in a subset of RA patients.

Subject headings

MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin -- Reumatologi och inflammation (hsv//swe)
MEDICAL AND HEALTH SCIENCES -- Clinical Medicine -- Rheumatology and Autoimmunity (hsv//eng)

Keyword

factor-like domain
ii collagen
disease
binding
comp
association
smoking
arrays
serum
site
Rheumatology

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ref (subject category)
art (subject category)

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By the author/editor: Ge, C. R.; Dobritzsch, Dore ...; Lonnblom, E.; Liang, B. B.; Cai, W. W.; Fahlquist-Hagert ...; show more...; Li, T. T.; Kastbom, Alf; Gjertsson, Inger ...; Dobritzsch, D.; Holmdahl, R.; Tong, Dongmei; show less...

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

Articles in the publication: Arthritis & Rheu ...

By the university: University of Gothenburg; Uppsala University; Karolinska Institutet; Linköping University

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