Trans-signaling through the agonistic sIL-6R and an imbalanced inflammatory response are associated with increased susceptibility to Graves' disease.

BACKGROUND

Excessive inflammatory cytokines are known to impact immune response and autoimmunity. In this study, we quantified the level of interleukin (IL)-6, soluble IL-6 receptor (sIL-6R), glycoprotein 130 (sgp130) and IL-10 to determine their involvement in the pathogenesis of Graves' disease (GD), in addition to the assessment serum cytokines IL-6, sIL-6R, sgp130, and IL-10 performance as biomarkers for the diagnosis of GD.

METHODS

A total of 20 patients with GD and 21 healthy individuals from the Indonesian population were enrolled. The serum concentrations of the selected cytokines were quantified using the ELISA method. Thyroid-stimulating hormone (TSH), free thyroxine (FT4), free triiodothyronine (FT3), and TSH receptor antibody (TSHR-Ab) were also evaluated. Comparative analysis was performed in addition to the assessment of the diagnostic performance of cytokines using receiver-operating-curve (ROC) analysis. Pearson's correlation coefficient was used to assess the relationship between 2 quantitative variables.

RESULTS

Patients with GD had a higher IL-6, sIL-6R, and IL-6/IL-10 ratio but a lower sgp130/sIL-6R/IL-6 ratio vs controls. The ROC curve analysis showed that the sgp130/sIL-6R/IL-6 ratio exhibited better performance than IL-6, sIL-6R, and IL-6/IL-10 ratio in diagnosing GD. In addition, serum levels of IL-6, sIL-6, and IL-10 were associated with thyroid parameters, including TSHR-antibody (Ab) levels.

CONCLUSION

IL-6 trans-signaling and imbalance of inflammatory response could be prominent factors in the pathogenesis of GD.