Anti-citrullinated protein antibodies as biomarkers in rheumatoid arthritis

ABSTRACT

Introduction

The serological biomarker anti-citrullinated protein antibodies (ACPAs) may have several functions but is especially important for the diagnosis of rheumatoid arthritis (RA) along with clinical symptoms.

Areas covered

This review provides an overview of ACPAs, which are useful in RA diagnostics and may improve our understanding of disease etiology. PubMed was searched with combinations of words related to antibodies recognizing epitopes containing the post-translationally modified amino acid citrulline in combination with rheumatoid arthritis; cyclic citrullinated peptide, CCP, anti-CCP, anti-citrullinated protein antibodies, ACPA, citrullination, peptide/protein arginine deiminase, PAD, filaggrin, vimentin, keratin, collagen, perinuclear factor, EBNA1, EBNA2, and others. From this search, we made a qualitative extract of publications relevant to the discovery, characterization, and clinical use of these antibodies in relation to RA. We highlight significant findings and identify areas for improvement.

Expert opinion

ACPAs have high diagnostic sensitivity and specificity for RA and recognize citrullinated epitopes from several proteins. The best-performing single epitope originates from Epstein–Barr Virus nuclear antigen 2 and contains a central Cit-Gly motif, which is recognized by ACPAS when located in a flexible peptide structure. In addition, ACPAs may also have prognostic value, especially in relation to early treatment, although ACPAs' main function is to aid in the diagnosis of RA.

KEYWORDS:

• Anti-citrullinated protein antibodies
• peptide backbone
• peptidyl-arginine deiminase
• rheumatoid arthritis
• rheumatoid factor

Article highlights

• Anti-citrullinated protein antibodies (ACPAs) have high diagnostic sensitivity and specificity for rheumatoid arthritis (RA)

• A major part of ACPAs is promiscuous and recognize citrulline often associated with glycine

• The best performing single ACPA substrate is derived from Epstein–Barr virus (EBV) nuclear antigen 2

• Studies support that ACPAs may have prognostic value, especially in relation to early treatment of RA

• Rheumatoid factors (RFs) and ACPAs may supplement each other in RA diagnostics, prognostics, and treatment monitoring

Declaration of interest

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Reviewers disclosure

Peer reviewers on this manuscript have no relevant financial relationships or otherwise to disclose.

Additional information

Funding

This paper was not funded.