Elsevier

Joint Bone Spine

Volume 76, Issue 5, October 2009, Pages 501-507
Joint Bone Spine

Original article
What can we learn from the presence of anti-cyclic citrullinated peptide antibodies in systemic lupus erythematosus?

https://doi.org/10.1016/j.jbspin.2008.11.007Get rights and content

Abstract

Background

Anti-cyclic citrullinated peptide (anti-CCP) antibodies have proved to be a specific marker for the diagnosis of rheumatoid arthritis (RA). However, the antibodies can also be detected in other rheumatic diseases, especially systemic lupus erythematosus (SLE). Recent studies have shown anti-CCP antibodies are associated with erosive arthritis in SLE patients. Since erosive arthritis is not common in SLE and many patients with non-erosive arthritis also have anti-CCP antibodies, the clinical significance of anti-CCP antibodies in SLE needs to be further studied.

Objective

To investigate the prevalence and clinical significance of anti-CCP antibodies in Chinese SLE patients.

Methods

Serum samples from 138 SLE patients were examined for anti-CCP with the second generation anti-CCP detection kit. The associations of anti-CCP with clinical and laboratory features, especially arthritis, in such SLE patients were analyzed.

Results

The prevalence of anti-CCP was 13.8% (19/138) in Chinese SLE patients. Seventy of 138 SLE patients had experienced arthritis, of whom 14 patients were anti-CCP+. Significantly, anti-CCP antibodies were more frequently found in SLE patients with arthritis than without arthritis (20% vs 7.4%, P < 0.05). A statistical correlation between anti-CCP and rheumatoid factor (RF) was found in SLE patients with arthritis (r = 0.36, P = 0.002). The frequency of arthritis was significantly higher in SLE patients with anti-CCP than without (73.7% vs 47.1%,P < 0.05). Eight out of 138 SLE patients showed joint erosions on radiographs. When compared with anti-CCP− patients, erosive arthritis occurred more often in anti-CCP+ patients (35.7% vs 5.4%, P < 0.001). Interestingly, two patients without anti-CCP and RF who had erosive arthritis were anti-RA33 antibodies positive. All of 8 SLE patients with erosive arthritis in our study fulfilled 1987 ACR criteria for RA. With regard to other clinical and laboratory features, there were no differences between SLE patients with arthritis and without or between anti-CCP+ patients and anti-CCP- patients.

Conclusions

Anti-CCP antibodies have a frequency of 13.8% in Chinese SLE patients and its presence is closely associated with the onset of arthritis and bone erosion.

Introduction

Systemic lupus erythematosus (SLE) is a complex rheumatic disease characterized by multiple organ damage and the presence of autoantibodies. Among the diverse clinical manifestations, arthritis is one of the most common features. Sometimes arthritis in SLE patients as the single sign occurs in the initial stage of the disease and is very similar to rheumatoid arthritis (RA). In addition, most rheumatoid arthritis (RA) patients develop erosive arthritis over 2–3 years from the onset [1], whereas about 5% of patients with SLE also have joint erosions [2], [3]. Consequently, early diagnosis of SLE patients with arthritis is somewhat difficult and often confused with RA. Erosions can lead to joint destruction and dysfunction, which eventually affect the quality of life of the patients. Clinically, how to efficiently distinguish between the two diseases at the onset and predict the outcome of arthritis in SLE patients are questions that rheumatologists need to ask.

In the past few years, numerous studies have proved that anti-cyclic citrullinated peptide (CCP) antibodies are a diagnostic marker for RA with high sensitivity and specificity [4], [5], [6]. Additionally, the presence of this antibody is closely associated with radiographic progression and prognosis of RA [7], [8], [9]. However, recent research has shown that anti-CCP antibodies can be also detected in other autoimmune diseases including psoriatic arthritis (PsA) [10], juvenile idiopathic arthritis (JIA) [11], Sjögren’s syndrome [12] and SLE [13], [14], [15]. The presence of anti-CCP antibodies in these diseases, especially in SLE, may be helpful as a serum marker for predicting erosive arthritis [10], [11], [12], [13], [14], [15]. It is known that several antibodies are related to clinical features of SLE, such as the anti-double stranded DNA (anti-dsDNA) antibodies, which are related to lupus glomerulonephritis [16], and anti-SSA antibodies are associated with subacute cutaneous lupus and neonatal lupus [17], [18]. However, no antibodies were found to be related to SLE arthritis until anti-CCP antibodies appeared. Although it has been suggested that anti-CCP antibodies are associated with erosive arthropathy in SLE patients by several groups recently [13], [14], [15], the exact clinical significance of the presence of these antibodies in SLE remains unclear. For example, what is the association between anti-CCP antibodies and arthritis, not only erosive arthritis, in SLE patients? Are the SLE patients with anti-CCP antibodies destined to have erosive arthritis? Does the association established in the Caucasian population also exist in other ethnic groups?

With the above questions, this study was undertaken to determine the prevalence of anti-CCP antibodies and to estimate the clinical significance of anti-CCP in Chinese patients with SLE.

Section snippets

Patients and controls

One hundred and thirty-eight SLE patients, fulfilling the revised American College of Rheumatology (ACR) classification criteria (1997) for SLE [19], [20], were included in this study. The group comprised 134 women and 4 men with a median age of 36 years (range 15–83 years). The median duration of disease was 42 months (0.3–360 months). Clinical features for each patient were collected from the medical record database of Peking University People’s Hospital, including the presence of arthritis,

Prevalence of anti-CCP antibodies in SLE patients

The median levels of anti-CCP antibodies in SLE, RA and healthy individuals were 3.7 RU/ml, 55.7 RU/ml and 1.3 RU/ml, respectively. Nineteen of 138 (13.8%) SLE patients were positive for anti-CCP antibodies. As controls, anti-CCP antibodies were positive in 80% (56/70) of RA patients and none of the 100 healthy individuals. Among the three groups, the prevalence of anti-CCP was significantly different when compared with each other (P < 0.001) (Fig. 1).

Characteristics of SLE patients with arthritis

Seventy of 138 (50.7%) SLE patients had

Discussion

Anti-CCP antibodies have been considered as a high specific serologic marker for the diagnosis of RA since it was reported in 2000 [4]. Moreover, the second generation anti-CCP (anti-CCP2) assay was reported to have a higher sensitivity with similar specificity compared with the first generation assay [22]. However, it was noticed that anti-CCP antibodies could be detected in patients with non-RA diseases, including SLE, and even in normal subjects [23]. These patients or normal individuals

Acknowledgments

This study was supported by the grant from Hi-tech Research and Development Program of China (2006AA02Z4D0). We thank Dr Rulin Jia for kindly pro-viding technical assistance.

References (36)

  • L. Lutteri et al.

    Comparison of second- and third-generation anti-cyclic citrullinated peptide antibodies assays for detecting rheumatoid arthritis

    Clin Chim Acta

    (2007)
  • M. Bukhari et al.

    Time to first occurrence of erosions in inflammatory polyarthritis: results from a prospective community-based study

    Arthritis Rheum

    (2001)
  • M.G. Cohen et al.

    Concurrence of rheumatoid arthritis and systemic lupus erythematosus: report of 11 cases

    Ann Rheum Dis

    (1987)
  • A.S. Fischman et al.

    The coexistence of rheumatoid arthritis and systemic lupus erythematosus: a case report and review of the literature

    J Rheumatol

    (1981)
  • G.A. Schellekens et al.

    The diagnostic properties of rheumatoid arthritis antibodies recognizing a cyclic citrullinated peptide

    Arthritis Rheum

    (2000)
  • K. Suzuki et al.

    High diagnostic performance of ELISA detection of antibodies to citrullinated antigens in rheumatoid arthritis

    Scand J Rheumatol

    (2003)
  • X. Zeng et al.

    Diagnostic value of anti-cyclic citrullinated peptide antibody in patients with rheumatoid arthritis

    J Rheumatol

    (2003)
  • A. Kastbom et al.

    Anti-CCP antibody test predicts the disease course during 3 years in early rheumatoid arthritis (the Swedish TIRA project)

    Ann Rheum Dis

    (2004)
  • E.J. Kroot et al.

    The prognostic value of anti-cyclic citrullinated peptide antibody in patients with recent-onset rheumatoid arthritis

    Arthritis Rheum

    (2000)
  • S.M. Bongi et al.

    Anti-cyclic citrullinated peptide antibodies are highly associated with severe bone lesions in rheumatoid arthritis: anti-CCP and bone damage in RA

    Autoimmunity

    (2004)
  • E. Korendowych et al.

    The clinical and genetic associations of anti-cyclic citrullinated peptide antibodies in psoriatic arthritis

    Rheumatology (Oxford)

    (2005)
  • O. Kasapçopur et al.

    Diagnostic accuracy of anti-cyclic citrullinated peptide antibodies in juvenile idiopathic arthritis

    Ann Rheum Dis

    (2004)
  • J.E. Gottenberg et al.

    Prevalence of anti-cyclic citrullinated peptide and anti-keratin antibodies in patients with primary Sjögren’s syndrome

    Ann Rheum Dis

    (2005)
  • R. Mediwake et al.

    Use of anti-citrullinated peptide and anti-RA33 antibodies in distinguishing erosive arthritis in patients with systemic lupus erythematosus and rheumatoid arthritis

    Ann Rheum Dis

    (2001)
  • I.E. Hoffman et al.

    Presence of rheumatoid factor and antibodies to citrullinated peptides in systemic lupus erythematosus

    Ann Rheum Dis

    (2005)
  • M.T. Chan et al.

    Associations of erosive arthritis with anti-cyclic citrullinated peptide antibodies and MHC class II alleles in systemic lupus erythematosus

    J Rheumatol

    (2008)
  • Y. Renaudineau et al.

    Association of alpha-actinin-binding anti-double-stranded DNA antibodies with lupus nephritis

    Arthritis Rheum

    (2006)
  • S.M. Purcell et al.

    Relationship between circulating anti-Ro/SS-A antibody levels and skin disease activity in subacute cutaneous lupus erythematosus

    Br J Dermatol

    (1987)
  • Cited by (34)

    • Rhupus: a systematic literature review

      2020, Autoimmunity Reviews
      Citation Excerpt :

      A better dynamic knowledge of the disease course would also help to divide patients into subgroups and identify, among both SLE and RA patients, those who have risk factors for an evolution towards rhupus, thus preventing the long-term consequences of joint and extra-articular involvement. For instance, some authors reported a statistical correlation between anti-CCP antibodies and general SLE-associated arthritis (both erosive and nonerosive) [68], but how we should monitor anti-CCP-positive patients without erosive arthritis remains to be determined. Further work would help to better divide patients into subgroups and determine the place of other autoantibodies or imaging [77].

    • Diagnostic potential of ultrasound in systemic lupus erythematosus patients with joint involvement: Relation to anticyclic citrullinated peptide (anti-CCP), disease activity and functional status

      2019, Egyptian Rheumatologist
      Citation Excerpt :

      Chan et al., [15] found a positive anti-CCP in one third of SLE cases with erosive arthritis. Also, Zhao et al., [18] found erosive arthritis in 5.8% of SLE patients and more that half of them were anti-CCP positive. Among the study limitations is the small number and corss sectional study design.

    • Joint involvement in systemic lupus erythematosus: From pathogenesis to clinical assessment

      2017, Seminars in Arthritis and Rheumatism
      Citation Excerpt :

      The evaluation of ACPA antibodies in SLE sera leads to controversial results, as underlined by the systematic review conducted by Budhram et al. [88]. Table 4 summarizes data concerning the prevalence of ACPA in different SLE populations [26,89–96]. Such studies, characterized by different sample size (from 11 to 231), identified a prevalence of ACPA in SLE patients ranging from 4.4% to 27.3%.

    View all citing articles on Scopus
    View full text