The use of synthetic peptides for detection of anti-citrullinated protein antibodies in rheumatoid arthritis

Nicole Hartwig Trier, Bettina Eide Holm, Julie Heiden, Ole Slot, Henning Locht, Bente Jensen, Hanne Lindegaard, Anders Svendsen, Christoffer Tandrup Nielsen, Søren Jacobsen, Elke Theander, Gunnar Houen

Research output: Contribution to journalJournal articleResearchpeer-review

Abstract

Rheumatoid arthritis (RA) is an autoimmune disease of unknown etiology. A characteristic feature of RA is the presence of anti-citrullinated protein antibodies (ACPA). Since ACPAs are highly specific for RA and are often present before the onset of RA symptoms, they have become valuable diagnostic and prognostic. As a result, several assays for detection of ACPAs exist, which vary in sensitivity and specificity. In this study, we analyzed the reactivity of RA sera to selected peptides by solid-phase immunoassays in order to develop an ACPA assay with improved sensitivity and specificity. ACPA levels were determined with respect to sensitivity and specificity in 332 serum samples using the newly developed peptide panel, which was compared to the commercial assays CCPlus (Eurodiagnostica) and CCP3.1 (Inova Diagnostics). A primary panel (peptides 814, 33062 and 33156) was identified, which obtained a sensitivity of 71%, while the complete peptide panel reacted with 79% of RA sera screened. Total specificities of 89% and 80% were obtained for the primary peptide panel and the complete peptide panel. Sensitivities for the commercial assays ranged between 71% and 76% and specificities between 88% and 90%. These findings indicate that the generated peptide panel is optimal for ACPA detection and able to compete with commercial available assays. Collectively, this study may contribute to characterize autoimmunity towards citrullinated proteins and to the development of new and improved diagnostic assays for detection of ACPA and determination of RA.

Original languageEnglish
JournalJournal of Immunological Methods
Volume454
Pages (from-to)6-14
ISSN0022-1759
DOIs
Publication statusPublished - Mar 2018

Keywords

  • Journal Article
  • Anti-citrullinated protein antibodies
  • Rheumatoid arthritis
  • Cyclic citrullinated peptides
  • Streptavidin capture enzyme-linked immunosorbent assay
  • Synthetic peptides
  • Predictive Value of Tests
  • Prognosis
  • Humans
  • Anti-Citrullinated Protein Antibodies/metabolism
  • Proteoglycans/chemical synthesis
  • Sensitivity and Specificity
  • Enzyme-Linked Immunosorbent Assay/methods
  • Peptides/chemical synthesis
  • Early Diagnosis
  • Arthritis, Rheumatoid/diagnosis

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