Antibody Response to Cyclic Citrullinated Peptides May Predict RA Onset

blood sample for clinical test
blood sample for clinical test
Investigators found data from a Chinese cohort that showed a specific biomarker with the presence of autoantibodies to citrullinated collagen type II epitopes that predict rheumatoid arthritis in patients several years before disease onset.

According to a study published in Rheumatology (Oxford), the identification of specific anti-citrullinated peptide antibodies in the sera of patients with rheumatoid arthritis (RA), but not other joint diseases, may help with the early detection and stratification of RA years before disease onset.

The investigators of this study sought to evaluate the prevalence and specificity of autoantibody responses to citrullinated cyclic peptides derived from collagen type II (CII) as sensitive biomarkers in individuals with RA. Using sera from a Chinese cohort of confirmed RA and osteoarthritis cases, the investigators designed a library of defined cyclic peptides.

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The study included 415 patients with RA, 304 patients with osteoarthritis, and 203 healthy controls. Investigators performed a bead-based multiplex assay to analyze the binding activity of autoantibodies to 54 cyclic 17-mer citrullinated CII peptides—which encompass all citrullinated epitopes associated with CII—and unmodified peptides among the arthritic groups. For comparison, a set of the top 10 cyclic citrullinated peptides were examined for autoantibody responses in the healthy cohort.

Autoantibody responses to most cyclic citrullinated CII peptides were higher in the RA group vs the osteoarthritis group, and patterns of peptide reactivity were notably more diverse among those with RA. When the investigators examined the performance of each peptide to distinguish RA from osteoarthritis, sera from the former showed a strong reactivity toward the citrullinated C1 (19-CIT), F4 (49-CIT), U1 (25-CIT), and E10 (38-CIT) CII epitopes. Furthermore, the investigators identified novel citrullinated epitopes (2-CIT and 46-CIT) as having a high diagnostic value for RA. In healthy individuals and patients with osteoarthritis, reactivity to the top 10 epitopes (including the newly identified epitopes) was minimal, suggesting that the high specificity in antibody response toward citrullinated peptides was attributed to patients with RA.

Limitations to the study included a cohort recruited from China, in which genetic differences may lead to a different epitope profile and antibody reactivity. Some individuals who participated in the study received traditional Chinese medicine instead of standard treatment for RA.

The investigators found a high prevalence of anticitrullinated CII antibodies in the sera of individuals with RA, along with diverse binding patterns against novel citrullinated CII epitopes. The investigators suggest that detection of autoantibody reactivity to defined cyclic citrullinated peptides may be useful in predicting the onset and subtype of RA.


Liang B, Ge C, Lönnblom E, et al. The autoantibody response to cyclic citrullinated collagen type II peptides in rheumatoid arthritis [published online March 19, 2019]. Rheumatology (Oxford). doi: 10.1093/rheumatology/kez073