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AB0085 Interaction of HLA-shared epitope (SE) and smoking on the development of ANTI-CCP positive rheumatoid arthritis in greek population
  1. EN Mole1,
  2. K Tarassi2,
  3. V Kitsiou2,
  4. T Athanassiades2,
  5. D Kouniaki2,
  6. K Soufleros2,
  7. C Korkou1,
  8. A Tsirogianni2,
  9. C Sfontouris1
  1. 1Department of Rheumatology
  2. 2Department of Immunology-Histocompatibility, Evangelismos General Hospital, Athens, Greece


Background Rheumatoid Arthritis (RA) is a complex, multifactorial autoimmune disease, whose etiopathogenesis involves genetic and environmental factors.

Objectives The aim of the study was the assessment of the association of HLA-DRB1*-SE in the presence/absence of anti-CCP autoimmunity in Greek patients with RA (smokers and non-smokers).

Methods Eighty-three (83) RA patients (41 smokers, 42 have never smoked) were typed for HLA-DRB1* alleles by molecular techniques (PCR-SSOP and -SSP). In 62 out of 83 (74.7%) anti-CCP abs were detected by ELISA.

Results In RA pts and in comparison to the controls, increased frequency of HLA-DRB1*01:01 (28.9% vs 6.8%, OR=4.4), *10:01 (16.9% vs 2.4%, OR=8.4), *04:01 (3.6% vs 2%, OR=1.8), *04:04 (7.2% vs 1%, OR=7.6) and *04:05 (15.7% vs 3.7%, OR=4.8), as well as decreased frequency of *04:02 (1.2% vs 2%, OR=0.6) and *04:03 (4.8% vs 6.8%, OR=0.7) were found. Among the RA patients, 77.1% possess 1SE vs 18.9% of controls (OR=14.4), whereas 10.8% possess 2SE vs 1% of controls (OR=11.8). In CCP (+) RA patients and in comparison to CCP (-) an increased frequency of HLA-DRB1*01:01 (27.4% vs 14.3%, OR=2.3) and *10:01 (21% vs 4.8%, OR=5.3) was observed. Furthermore, 88.7% of CCP (+) carry 1SE vs 42.9% of CCP (-) patients (OR=10.5). CCP (+) smokers patients in comparison to CCP (+) non-smokers are presented with an increased frequency of DRB1*01:01 (41.9% vs 12.9%, OR=4.9). Among the CCP (+) smokers, 96.8% possess 1SE vs 80.6% of CCP (+) non-smokers (OR=7.2), whereas 12.9% possess 2SE vs 12.9% of CCP (+) non-smokers (OR=1).

Conclusions a) An increased frequency of HLA-DRB1*01:01, *10:01, *04:05 alleles, as well as the protective role of *04:02, *04:03 alleles in Greek patients with RA were confirmed b) The presence of any SE, particularly *10:01 allele, strongly influences the production of anti-CCP abs and c) Interaction between smoking and any SE, particularly *01:01 allele, is associated with anti-CCP positive RA in Greek patients.


  1. Klareskog L, Stolt P, Lundberg K, Kallberg H, Bengtsson C, Grunewald J, et al. A new model for an etiology of rheumatoid arthritis: smoking may trigger HLA-DR (shared epitope)-restricted immune reactions to autoantigens modified by citrullination. Arthritis and rheumatism. 2006;54(1):38–46.

  2. Ioannidis JP, Tarassi K, Papadopoulos IA, Voulgari PV, Boki KA, Papasteriades CA, et al. Shared epitopes and rheumatoid arthritis: disease associations in Greece and meta-analysis of Mediterranean European populations. Seminars in arthritis and rheumatism. 2002;31(6):361–70.

  3. Lee YH, Bae SC, Song GG. Gene-environmental interaction between smoking and shared epitope on the development of anti-cyclic citrullinated peptide antibodies in rheumatoid arthritis: a meta-analysis. International journal of rheumatic diseases. 2014;17(5):528–35.


Disclosure of Interest None declared

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