The use of chimeric vimentin citrullinated peptides for the diagnosis of rheumatoid arthritis

J Med Chem. 2011 Nov 10;54(21):7486-92. doi: 10.1021/jm200563u. Epub 2011 Oct 7.

Abstract

Rheumatoid arthritis (RA) is a chronic autoimmune disease that causes inflammation and, in many cases, destruction of the joints. To prevent progressive and irreversible structural damage, early diagnosis of RA is of paramount importance. The present study addresses the search of new RA citrullinated antigens that could supplement or complement diagnostic/prognostic existing tests. With this aim, the epitope anticitrullinated vimentin antibody response was mapped using synthetic peptides. To improve the sensitivity/specificity balance, a vimentin peptide that was selected, and its cyclic analogue, were combined with fibrin- and filaggrin-related peptides to render chimeric peptides. Our findings highlight the putative application of these chimeric peptides for the design of RA diagnosis systems and imply that more than one serological test is required to classify RA patients based on the presence or absence of ACPAs. Each of the target molecules reported here (fibrin, vimentin, filaggrin) has a specific utility in the identification of a particular subset of RA patients.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Amino Acid Sequence
  • Arthritis, Rheumatoid / blood
  • Arthritis, Rheumatoid / diagnosis*
  • Arthritis, Rheumatoid / immunology
  • Autoantibodies / blood
  • Citrulline / chemistry
  • Citrulline / immunology
  • Citrulline / metabolism*
  • Enzyme-Linked Immunosorbent Assay
  • Epitopes
  • Female
  • Fibrin / chemistry
  • Fibrin / immunology
  • Filaggrin Proteins
  • Humans
  • Intermediate Filament Proteins / chemistry
  • Intermediate Filament Proteins / immunology
  • Male
  • Middle Aged
  • Molecular Sequence Data
  • Peptide Library
  • Peptides* / chemical synthesis
  • Peptides* / immunology
  • Peptides, Cyclic / chemical synthesis
  • Peptides, Cyclic / immunology
  • Sensitivity and Specificity
  • Solid-Phase Synthesis Techniques
  • Vimentin / chemistry
  • Vimentin / immunology
  • Vimentin / metabolism*

Substances

  • Autoantibodies
  • Epitopes
  • FLG protein, human
  • Filaggrin Proteins
  • Intermediate Filament Proteins
  • Peptide Library
  • Peptides
  • Peptides, Cyclic
  • Vimentin
  • Citrulline
  • Fibrin