FRI0413 Aryl hydrocarbon receptor expression is associated with lung involvement in systemic sclerosis
Authors: H. Takei, H. Yasuoka, K. Yoshimoto, K. Yamaoka, T. Takeuchi
Journal: Annals of the Rheumatic Diseases (2018)

<h3>Background</h3> Systemic sclerosis (SSc) is characterised by autoantibody production, microvascular injury and systemic excessive fibrosis<sup>1)</sup>. Genetic and environmental factors are thought to be important for the trigger of development of the disease, however, direct connexion between these factors and pathogenesis of SSc is not yet elucidated<sup>23</sup>. Recent reports showed that environmental toxic pollutants, such as dioxins, play a significant role in the disturbance of immune system and the trigger of autoimmunity through binding aryl hydrocarbon receptor (AhR)<sup>4)5)</sup>. However, little is known about the association between AhR and pathogenesis of SSc yet. <h3>Objectives</h3> To elucidate the association between AhR and the clinical characteristics of SSc. <h3>Methods</h3> Twenty-one patients with SSc who fulfilled 2013 ACR/EULAR classification criteria and 10 healthy controls (HC) were analysed. Peripheral blood mononuclear cells (PBMCs) were isolated from heparinized whole blood by using gradient centrifugation and total RNA was prepared from PBMCs. Expression of <i>Ahr</i> mRNA was detected by quantitative polymerase chain reaction and standardised by mRNA level of <i>18S</i> ribosomal RNA in each sample. Level of <i>Ahr</i> mRNA in the cells was compared between SSc and HC and also between SSc patients with and without various clinical features. <h3>Results</h3> The proportion of diffuse cutaneous subset (dcSSc) was 33%. Mean disease duration was 9±9 years. The positive proportion of anticentromere antibodies, anti-topoisomerase I antibodies, anti-U1 ribonucleoprotein antibody, anti-RNA polymerase III antibody and antinuclear antibody positive without SSc-specific antibodies among 21 patients were 33.3%, 33.3%, 4.8%, 9.5% and 9.5%, respectively. Antinuclear antibody was negative in 2 (9.5%) patients. <i>Ahr</i> mRNA expression level was tended to be higher in SSc compared to HC (1.7±1.1 versus 1.2±0.6, p<i>=</i>0.1). Notably, the expression level of <i>AhR</i> mRNA in dc SSc was tended to be higher than that of limited cutaneous SSc (p=0.15), whereas no significant difference was detected between with or without SSc related autoantibodies, vasculopathy such as pulmonary arterial hypertension or digital tip ulcer. Importantly, the expression level of <i>Ahr</i> mRNA was significantly higher in patients with interstitial lung disease (ILD) (n=14) than those without (n=7) (2.0±1.1 versus 1.0±0.4, p<i>&lt;</i>0.05). Furthermore, <i>AhR</i> mRNA expression level was significantly and negatively correlated with DLCO% predicted (r=−0.57, p<i>&lt;</i>0.05). <h3>Conclusions</h3> Expression level of Ahr mRNA was higher in patients with SSc, especially in SSc patients with ILD. In addition, AhR expression level was correlated with a parameter of pulmonary function test, DLCO% predicted. These results collectively suggest that AhR possibly plays an important role in the disease process of ILD in SSc. <h3>References</h3> [1] Nat Rev Rheumatol2013;9(8):451–64. [2] Nat. Rev. Rheumatol2014;10:671–681. [3] Semin. Immunopathol2015;37:463–473. [4] Annu Rev Immunol2014;32:403–32. [5] Nature. 2008;453(7191):65–71. <h3>Disclosure of Interest</h3> None declared