Cross-reactivity of a human IgG1 anticitrullinated fibrinogen monoclonal antibody to a citrullinated profilaggrin peptide

Authors

  • Nicole Hartwig Trier,

    Corresponding author
    1. Department of Clinical Biochemistry, Immunology and Genetics, Statens Serum Institut, Artillerivej 5, 2300 Copenhagen S, Denmark
    2. Department of Drug Design and Pharmacology, Faculty of Health and Medical Sciences, University of Copenhagen, Universitetsparken 2, 2100 Copenhagen Ø, Denmark
    • Department of Clinical Biochemistry, Immunology, and Genetics, Statens Serum Institut, Artillerivej 5, 2300 Copenhagen S, Denmark
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  • Maria Louise Leth,

    1. Department of Clinical Biochemistry, Immunology and Genetics, Statens Serum Institut, Artillerivej 5, 2300 Copenhagen S, Denmark
    2. Department of Drug Design and Pharmacology, Faculty of Health and Medical Sciences, University of Copenhagen, Universitetsparken 2, 2100 Copenhagen Ø, Denmark
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  • Paul Robert Hansen,

    1. Department of Drug Design and Pharmacology, Faculty of Health and Medical Sciences, University of Copenhagen, Universitetsparken 2, 2100 Copenhagen Ø, Denmark
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  • Gunnar Houen

    1. Department of Clinical Biochemistry, Immunology and Genetics, Statens Serum Institut, Artillerivej 5, 2300 Copenhagen S, Denmark
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Abstract

Rheumatoid arthritis (RA) is the most common autoimmune rheumatic disease. It is characterized by persistent joint inflammation, resulting in loss of joint function, morbidity and premature mortality. The presence of antibodies against citrullinated proteins is a characteristic feature of RA and up to 70% of RA patients are anticitrullinated protein antibody (ACPA) positive. ACPA responses have been widely studied and are suggested to be heterogeneous, favoring antibody cross-reactivity to citrullinated proteins. In this study, we examined factors that may influence cross-reactivity between a commercial human anticitrullinated fibrinogen monoclonal antibody and a citrullinated peptide. Using a citrullinated profilaggrin sequence (HQCHQEST- Cit-GRSRGRCGRSGS) as template, cyclic and linear truncated peptide versions were tested for reactivity to the monoclonal antibody. Factors such as structure, peptide length and flanking amino acids were found to have a notable impact on antibody cross-reactivity. The results achieved contribute to the understanding of the interactions between citrullinated peptides and ACPA, which may aid in the development of improved diagnostics of ACPA.

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