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

Abstract

Objective-Anti-cyclic citrullinated peptide (CCP) antibodies are a serological marker for rheumatoid arthritis (RA); up to 10%-15% of patients with systemic lupus erythematosus (SLE) are also positive. While anti-CCP in RA is citrulline-dependent, anti-CCP in some other diseases is citrulline-independent and reacts with both CCP and the unmodified (arginine-containing) cyclic arginine peptide (CAP). We investigated the citrulline dependence of anti-CCP and its significance in the arthritis of SLE.Methods-IgG anti-CCP was compared by ELISA to anti-CAP in sera from patients with SLE (n = 335) and RA (n = 47) and healthy controls (n = 35). SLE patients were divided into 5 groups based on their joint involvement: subset I: deforming/erosive arthritis (n = 20); II: arthritis fulfilling (or likely fulfilling) American College of Rheumatology criteria for RA but without erosions (n = 18); III: joint swelling but not fulfilling RA criteria (n = 39); IV: arthritis without documented joint swelling (n = 194); and V: no arthritis (n = 58).Results-Anti-CCP (> 1.7 units) was found in 68% (32/47) of patients with RA and 17% (55/329) of those with SLE. It was more common in SLE patients with deforming/erosive arthritis (38%). High anti-CCP (> 10 units) was found in RA (26%) and deforming/erosive SLE (12%). High anti-CCP/CAP ratios (> 2, indicating a selectivity to CCP) were found in 91% of anti-CCP-positive RA and 50% of anti-CCP-positive SLE patients with deforming/erosive arthritis. Patients from subset II did not have high anti-CCP/CAP. Conclusion-Citrulline dependence or high levels (> 10) of anti-CCP were common in SLE patients with deforming/erosive arthritis, while most anti-CCP in SLE patients was citrullineindependent. This may be useful in identifying a subset of SLE patients with high risk for development of deforming/erosive arthritis.

Anti-cyclic citrullinated peptide antibodies in systemic lupus erythematosus patients with articular involvement: a predictive marker for erosive disease?

“…All patients were positive for antinuclear antibodies detected by indirect immunofluorescence on Hep2 cells. Anti-CCP antibodies were found in 15 patients (7%) and these appeared to be distributed differently among the differ-original article (6,12,13) and then confirmed in some larger samples of SLE patients with arthritis (9,(14)(15)(16)(17)(18). Two of these studies (6,17) proposed that anti-CCP antibodies Sle, systemic lupus erythematosus; n, number of patients; SD, standard deviation; anti-ccP, anti-cyclic citrullinated peptide antibodies; crP, c reactive protein; rF, rheumatoid factor; *anti-ccP, erosive vs deforming arthritis: P=0.031; erosive vs non-erosive non-deforming arthritis: P=0.002; **increased crP, erosive vs non-deforming arthritis: P<0.001, deforming vs non-erosive non-deforming arthritis: P<0.001; °rF positivity, erosive vs non-erosive non-deforming arthritis: P=0.008; °°anti-ccP and rF positivity, erosive vs non-erosive non-deforming arthritis: P=0.031; §anti-ccP and/or rF positivity, erosive vs non-erosive non-deforming arthritis: P=0.002.…”

Respiratory Distress and Nephropathy in a Young Male With Small‐Joint Polyarthritis

“…In the absence of mechanism and discerning phenotype, it is difficult to differentiate between a true overlap syndrome and a sporadic occurrence of antisynthetase syndrome and RA. The simultaneous appearance of anti-CCP antibodies and antiJo-1 antibodies has been reported only in a small group of patients with antisynthetase syndrome and arthritis (16), raising the possibility of false anti-CCP antibody positivity, reported frequently in patients with other connective tissue diseases (17). The interpretability of commercial anti-CCP assays is limited by the absence of controls for both unspecific background binding or citrulline-independent reactivity with the cyclic peptide.…”

Anticyclic Citrullinated Peptide Antibodies in Patients with Rheumatic Diseases other than Rheumatoid Arthritis: Clinical or Pathogenic Significance?

“…It should be remembered that a close association between erosions and anti-CCP has been shown not only in RA 11,12 . These observations raised the question of the diagnostic significance of these autoantibodies in CTD.…”