Anticyclic citrullinated peptide antibodies in patients with mixed connective tissue disease

Abstract

The clinical significance of anticyclic citrullinated peptide (CCP) antibodies in patients with mixed connective tissue disease (MCTD) was assessed. Altogether, 86 sera from MCTD patients, 96 from rheumatoid arthritis (RA) patients, 42 from systemic lupus erythematosus (SLE) patients, 23 from systemic sclerosis (SSc) patients, 21 from polymyositis/dermatomyositis (PM/DM) patients, and 17 from those with Sjögren's syndrome (SjS) were tested for anti-CCP antibodies using an enzyme-lined immunosorbent assay. Among the 96 RA patients, anti-CCP antibodies were detected in 85%, with the frequency being significantly higher than in MCTD, SLE, SSc, PM/DM, and SjS patients (9%, 14%, 13%, 14%, and 18%, respectively; P < 0.001). Among eight MCTD patients who fulfilled the diagnostic criteria for RA, only 50% had anti-CCP antibodies, and the prevalence was significantly lower than for all RA patients (p < 0.01). All eight patients who fulfilled the criteria for RA had overlap of SLE and SSc, except one patient, whereas the four anti-CCP-positive patients who did not fulfill the criteria for RA had SjS without overlapping features of SLE and SSc; moreover, most of their antibody titers were low. These results suggested that anti-CCP antibodies are associated with RA in MCTD patients, but careful diagnosis of RA is required if patients with low titers of anti-CCP antibodies lack overlapping SLE and SSc.

Citrulline Dependence of Anti-Cyclic Citrullinated Peptide Antibodies in Systemic Lupus Erythematosus as a Marker of Deforming/Erosive Arthritis

“…The criteria used to select subjects were quite different among the studies; deforming or erosive arthropathy was used in some18,20–22, while others were based on ACR criteria for RA13,19, suggesting that variability in patient selection criteria may be partly responsible for the inconsistent results. Two studies that used deformity or erosion as selection criteria18,22 showed low frequencies (13% and 7%, respectively) of anti-CCP, similar to our present study, whereas others that primarily used erosion20,21 reported a high prevalence (80% and 50%, respectively; Table 1).…”

“…However, a detailed description of the arthritis seen in these patients was not given16. Conversely, those studies that have described an association of deforming or erosive arthropathy in SLE with anti-CCP positivity did not verify the citrulline dependence of anti-CCP in these patients13,18–22. SLE in this subset may have a pathogenesis similar to RA and thus have citrulline-dependent anti-CCP antibodies, whereas anti-CCP in other subsets of SLE may be citrulline-independent.…”

Antibodies to Citrullinated Vimentin are a Specific and Sensitive Marker for the Diagnosis of Rheumatoid Arthritis

“…However, while IgM RF concentrations have been found to decrease with treatment (DMARDS with/out infliximab), anti-CCP antibody concentrations do not appear to change [7], limiting the use of anti-CCP as a marker of disease activity and precluding its application as an indicator of response to treatment. There is an increasing evidence that anti-CCP antibodies are also detected in patients with other connective tissue diseases including Sjögren's syndrome, systemic lupus erythematosus, systemic sclerosis, mixed connective tissue disease, and idiopathic inflammatory myositis [23,24].…”

Clinical interpretation of antinuclear antibody tests in systemic rheumatic diseases

“…The frequencies of anti-CCP and rheumatoid factor (RF) are both *70%; however, anti-CCP is much more specific for RA. Nevertheless, anti-CCP may be positive in up to 10-20% of other rheumatic diseases and associated with chronic arthritis or Jaccoud'stype arthritis in SLE [49]. Anti-CCP in nonrheumatic disease patients is less extensively studied, and one may find unexpected positives in infections, such as in patients with pulmonary tuberculosis [50].…”