A Systematic Review of Serum Biomarkers Anti-Cyclic Citrullinated Peptide and Rheumatoid Factor as Tests for Rheumatoid Arthritis

Abstract

This systematic review assesses the current status of anti-cyclic citrullinated peptide (anti-CCP) and rheumatoid factor (RF) tests in the diagnosis and prognosis of rheumatoid arthritis (RA). We reviewed publications on tests and biomarkers for early diagnosis of RA from English-language MEDLINE-indexed journals and non-MEDLINE-indexed sources. 85 publications were identified and reviewed, including 68 studies from MEDLINE and 17 non-MEDLINE sources. Anti-CCP2 assays provide improved sensitivity over anti-CCP assays and RF, but anti-CCP2 and RF assays in combination demonstrate a positive predictive value (PPV) nearing 100%, greater than the PPV of either of the tests alone. The combination also appears to be able to distinguish between patients whose disease course is expected to be more severe and both tests are incorporated in the 2010 ACR Rheumatoid Arthritis Classification Criteria. While the clinical value of anti-CCP tests has been established, differences in cut-off values, sensitivities and specificities exist between first-, second- and third-generation tests and harmonization efforts are under way. Anti-CCP and RF are clinically valuable biomarkers for the diagnosis and prognosis of RA patients. The combination of the two biomarkers in conjunction with other clinical measures is an important tool for the diagnosis and management of RA patients.

Interpreting Studies of Diagnostic Accuracy

“…Their results seem to be at odds with previous findings, which have shown the high diagnostic accuracy of anti-CCP tests for differential diagnosis of RA 2,3 . It is important, therefore, to consider how to appropriately interpret studies of diagnostic accuracy and assess generalizability.…”

Meta-analysis: diagnostic accuracy of anti-cyclic citrullinated peptide 2 antibody and anti-cyclic citrullinated peptide 3 antibody in rheumatoid arthritis

“…Early and accurate diagnosis of rheumatoid arthritis could decrease the morbidity of functional disability and improve quality of life. With the desire to resolve the problem, most rheumatologists recommend measuring anti-CCP antibody and RF for early rheumatoid arthritis [45,46]. Because it is costly to treat persons who were misdiagnosed with rheumatoid arthritis, we need to consider the risks and benefits of such an approach.…”

Unique Correlation Between Mutated Citrullinated Vimentine IgG Autoantibodies and Markers of Systemic Inflammation in Rheumatoid Arthritis Patients

“…However, it can be detected in other autoimmune disorders, such as Sjögren's syndrome (SS), and in various non autoimmune conditions, including infectious diseases, as well as in healthy subjects. In this setting, the deeper knowledge of the pathogenic mechanisms underlying synovial rheumatoid damage allowed the identification of a variety of citrullinated proteins that may act as potential auto antigens [8]. A true breakthrough in the RA serologic profile was the identification of amino acid citrulline as the main compound of the antigenic determinant recognized by RA specific autoantibodies [2,9].…”