Cross-reactivity of a human IgG₁ anticitrullinated fibrinogen monoclonal antibody to a citrullinated profilaggrin peptide.
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.
Department of Clinical Biochemistry, Immunology and Genetics, Statens Serum Institut, Artillerivej 5, 2300 Copenhagen S, Denmark. nhp@ssi.dk
Nicole Hartwig
NH
Trier
Maria Louise
ML
Leth
Paul Robert
PR
Hansen
Gunnar
G
Houen
D000595:Amino Acid Sequence; D000911:Antibodies, Monoclonal / Q000276:immunology*; D001172:Arthritis, Rheumatoid / Q000276:immunology; D002956:Citrulline / Q000737:chemistry / Q000276:immunology*; D003429:Cross Reactions; D005340:Fibrinogen / Q000737:chemistry / Q000276:immunology*; D000091344:Filaggrin Proteins; D006801:Humans; D007074:Immunoglobulin G / Q000276:immunology*; D007381:Intermediate Filament Proteins / Q000737:chemistry / Q000276:immunology*; D008969:Molecular Sequence Data; D010456:Peptides, Cyclic / Q000737:chemistry / Q000276:immunology
D000911:Antibodies, Monoclonal; D000091344:Filaggrin Proteins; D007074:Immunoglobulin G; D007381:Intermediate Filament Proteins; D010456:Peptides, Cyclic; D002956:Citrulline; D005340:Fibrinogen