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SAT0594 Will Anti-Cyclic Citrullinated Peptide Antibody-Positive Connective Tissue Disease Patients Develop Rheumatoid Arthritis? Association with HLA-DRB1 Shared Epitope
  1. S. Nakabo1,
  2. T. Iwasaki1,
  3. K. Ohmura1,
  4. C. Terao2,
  5. K. Murakami1,
  6. R. Nakashima1,
  7. M. Hashimoto3,
  8. Y. Imura1,
  9. N. Yukawa1,
  10. H. Yoshifuji1,
  11. Y. Miura4,
  12. K. Yurugi4,
  13. T. Maekawa4,
  14. T. Fujii3,
  15. T. Mimori1,3
  1. 1Department of Rheumatology and Clinical Immunology
  2. 2Center for Genomic Medicine
  3. 3Department of the Control for Rheumatic Diseases, Kyoto University
  4. 4Department of Transfusion Medicine and Cell Therapy, Kyoto University Hospital, Kyoto, Japan


Background Anti-cyclic citrullinated peptide antibody (aCCP) is a widely-used diagnostic marker for rheumatoid arthritis (RA). In spite of its very high specificity, it is also reported that 5 to 10% of non-RA connective tissue disease (CTD) patients are positive for aCCP [1]. It is unknown whether such aCCP-positive non-RA CTD patients may develop RA later. There are few reports that referred long term outcome of aCCP-positive CTD patients.

Objectives To investigate whether aCCP-positive non-RA CTD patients finally develop RA, and to find out predictive factors of RA development.

Methods Non-RA CTD patients were selected from our CTD database of Kyoto University as of December 2012. Anti-CCP was measured by the second generation ELISA kit (MESACUP-2 test CCP; MBL Inc., Japan).

HLA-DRB1 allele was typed by WakFlow system and the shared epitope (SE) was defined by the HLA-DRB1 alleles shown in the reference [2].

Clinical information was obtained from the clinical records and also the questionnaire to the attending doctors.

Results 842 CTD patients with aCCP information were enrolled. 58 patients had fulfilled the 1987 ACR revised criteria of RA and had been followed as overlap cases, of which 35 patients (60%) were positive for aCCP. On the other hand, out of 784 patients who had not fulfilled the RA criteria, 37 patients (4.7%) were positive for aCCP. Details are shown in the Table 1 and Figure 1.

During the average follow-up period of 4.8 years, none of the 37 non-RA CTD patients except one case developed RA by fulfilling the 1987 ACR revised RA criteria. Hands and feet X-ray were taken in 27 out of the 37 non-RA CTD patients, and none of them have developed bone erosions.

We compared the clinical characteristics between 36 aCCP-positive RA/CTD overlapped patients and 36 aCCP-positive non-RA CTD patients, and the former showed significantly lower rheumatoid factor (RF) positivity, lower incidence of joint symptoms, less DMARDs usage, and more glucocorticoid usage. Titer of aCCP was not significantly different between these two groups.

HLA DRB1 allele was typed in 26 out of 36 non-RA CTD patients and 28 out of 36 RA/CTD overlapped patients. The number of patients possessing SE were 8 (31%) and 18 (64%), respectively, the deference of which is statistically significant (p=0.01).

Conclusions From our retrospective observation of follow-up period of 4.8 years in average, only one of 37 aCCP-positive non-RA CTD fulfilled the 1987 ACR revised RA criteria, but without bone erosions. The frequency of SE was significantly different between non-RA CTD patients and RA/CTD overlapped patients, which may suggest the utility of HLA typing to predict the future RA development. Because SE bind to citrullinated antigens [3], these results may also suggest that the epitope of aCCP in non-RA CTD is not dependent on citrullination.


  1. Aggarwal R. Arthritis Rheum (2009) 61: 1472-1483.

  2. Terao C. Ann Rheum Dis (2011) 70: 2134-2139.

  3. Scally S W. J Exp Med (2013) 210: 2569-2582.

Disclosure of Interest None declared

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