Session Title: Rheumatoid Arthritis - Human Etiology and Pathogenesis
Session Type: Abstract Submissions (ACR)
Smoking is an important player in the pathogenesis of rheumatoid arthritis (RA) being tightly connected to the genetic (carriage of HLA-DRB1 shared epitope) and serological (production of autoantibodies) risk factors for the development of RA. The molecular events connecting cigarette smoking to severe joint inflammation and low efficacy of anti-rheumatic drugs, are poorly understood. Adipokines is a family of signalling molecules originating from adipose tissue and regulating carbohydrate metabolism and soft tissue regeneration. In RA, adipokines are connected to the disease activity and progressive radiological joint damage. Numerous effects of adipokines are mediated through insulin receptor/insulin-like growth factor-1 receptor (IGF-1R) complex.
Here we address a potential connections between cigarette smoking and changes in IGF-1 signalling and adipokine network function in patients with RA.
543 patients from 2 independent RA cohorts (Göteborg, n=350 and Leiden, n=193) were included in this observational study. Patients were divided by their smoking habits defined as present smokers (n=126), ex smokers (n=177) and never smokers (n=240). Serum levels of total IGF-1 and adipokines (adiponectin, leptin, resistin and visfatin) were measured with sandwich ELISAs. The patient groups were compared by quantitative statistics and the association between smoking and serum parameters were evaluated by bivariate and multivariate correlation analysis.
The two studied cohorts differed in disease duration, where the Leiden cohort consisted of early RA patients (DD md 0.4 years), higher disease activity (DAS28 md 5.1) and higher VAS-pain (md 46mm), while the Göteborg cohort consisted of patients with established RA (DD md 7.5 years), low DAS28 (md 3.0) and VAS-pain (md 27mm). In both cohorts the smokers were more often men (P<0.001).
Serum levels of IGF-1 were significantly lower in the present smokers followed by ex smokers. RA patients who never smoked had significantly higher serum levels of IGF-1 (P<0.001). Levels of adiponectin were also higher in never smokers (P=0.002). The correlation between leptin and resistin observed in the whole material was significantly weaker in the present smokers (rho=0.357) compared to the never smokers (rho=0.520). The present smokers had stronger correlations between IGF-1 and leptin (rho=0.233, P=0.009), resistin (rho=0.210, P=0.018). These correlations were not observed in the never smokers or the ex smokers.
The logistic regression analysis showed that low levels of IGF-1 were associated with low levels of leptin and visfatin and with current smoking. Neither age, gender, DAS28 nor BMI was contributing significantly in the regression model. Clinical impact of low leptin levels evaluated in a different logistic regression model showed an association with high DAS28, male gender and high BMI.
Smoking is associated with lower serum levels of IGF-1 in RA patients. The link between IGF-1 and the adipokines network is dependent on the smoking habit of the patient, and potentially supporting sustained disease activity and reducing regeneration processes in the damaged arthritic joints in RA patients.
S. Töyrä Silfverswärd,
R. Doria Medina,
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ACR Meeting Abstracts - https://acrabstracts.org/abstract/smoking-functions-as-a-negative-regulator-of-igf-1-levels-and-adipokine-network-in-patients-with-rheumatoid-arthritis/