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Background <p>Rheumatoid arthritis (RA) is a complex, multifactorial autoimmune disease, whose aetiopathogenesis involves genetic and environmental factors. It remains unclear whether these factors influence the radiographic damage in RA patients. In this study we aimed to investigate the main effects of shared epitope (SE) alleles, smoking and anti-citrullinated protein antibodies (ACPAs), as well as their possible interaction on the radiographic outcome, in Greek patients with longstanding RA.</p> Methods <p>The study comprised of 300 Greek RA patients, 150 smokers and 150 non-smokers. ACPAs were determined by ELISA, HLA-DRB1 alleles were typed by molecular techniques. Radiographs of hands and feet were scored by modified Sharp/van der Heijde score (SHS).</p> Results <p>In total, 57.7% were ACPA positive and 64% possessed at least one copy of HLA-DRB1 allele. Predictors of radiographic severity were: presence of at least one copy of SE (B: 20.82 [17.76–23.87], <i>p</i> &lt; 0.001), ACPAs (B: 14.4 [10.96–17.84], <i>p</i> &lt; 0.001) and smoking history (B: 12.8 [9.36–16.25], <i>p</i> &lt; 0.001). Presence of *01:01, *04:05 and *10:01 alleles were also significantly associated with more radiographic damage (B: 11.63 [7.36–15.88], <i>p</i> &lt; 0.001, B: 8.8 [3.69–13.91], <i>p</i> = 0.001 and B: 15.56 [11.33–19.79], <i>p</i> &lt; 0.001), respectively. Furthermore, we observed an interaction between smoking, HLA-DRB1 SE alleles in respect to radiographic outcome only in seropositive RA, B: 10.13 [2.03–18.22], <i>p</i> = 0.015, <i>p</i> = 0.01 for interaction. There was no evidence of interaction effect when we analyzed the individual SE alleles.</p> Conclusions <p>We observed a significant gene-environmental interaction that influenced the radiographic severity in seropositive RA patients, in addition to its crucial role in the pathogenesis of seropositive RA.</p> Clinical trial number <p>Not applicable.</p>

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Impact of HLA-DRB1 SE, anti-citrullinated protein antibodies and smoking on radiographic outcome in Greek patients with Rheumatoid Arthritis

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  • 发表日期：

    2025年10月31日

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  • Evangelia N. Mole,
  • Katerina Tarassi,
  • Alexandra Tsirogianni,
  • Theophilos Athanassiades,
  • Vasiliki Kitsiou,
  • Diamanto Kouniaki,
  • Sousana Gazi,
  • Panagiotis Vlachoyiannopoulos

摘要

Background

Rheumatoid arthritis (RA) is a complex, multifactorial autoimmune disease, whose aetiopathogenesis involves genetic and environmental factors. It remains unclear whether these factors influence the radiographic damage in RA patients. In this study we aimed to investigate the main effects of shared epitope (SE) alleles, smoking and anti-citrullinated protein antibodies (ACPAs), as well as their possible interaction on the radiographic outcome, in Greek patients with longstanding RA.

Methods

The study comprised of 300 Greek RA patients, 150 smokers and 150 non-smokers. ACPAs were determined by ELISA, HLA-DRB1 alleles were typed by molecular techniques. Radiographs of hands and feet were scored by modified Sharp/van der Heijde score (SHS).

Results

In total, 57.7% were ACPA positive and 64% possessed at least one copy of HLA-DRB1 allele. Predictors of radiographic severity were: presence of at least one copy of SE (B: 20.82 [17.76–23.87], p < 0.001), ACPAs (B: 14.4 [10.96–17.84], p < 0.001) and smoking history (B: 12.8 [9.36–16.25], p < 0.001). Presence of *01:01, *04:05 and *10:01 alleles were also significantly associated with more radiographic damage (B: 11.63 [7.36–15.88], p < 0.001, B: 8.8 [3.69–13.91], p = 0.001 and B: 15.56 [11.33–19.79], p < 0.001), respectively. Furthermore, we observed an interaction between smoking, HLA-DRB1 SE alleles in respect to radiographic outcome only in seropositive RA, B: 10.13 [2.03–18.22], p = 0.015, p = 0.01 for interaction. There was no evidence of interaction effect when we analyzed the individual SE alleles.

Conclusions

We observed a significant gene-environmental interaction that influenced the radiographic severity in seropositive RA patients, in addition to its crucial role in the pathogenesis of seropositive RA.

Clinical trial number

Not applicable.