Evaluation of interleukins 37 and 38 and vitamin D status in the serum of women with Graves' disease

Abstract

Background: Graves' disease (GD) is an autoimmune thyroid disorder and recent studies have proposed a role for interleukin (IL)-37, IL-38, and vitamin D (VitD) in the pathophysiology of disease. Therefore, this study investigated the expression of IL-37, IL-38, and VitD in the serum of GD patients and correlations of their levels with some demographic and clinical characteristics.

Methods: Serum IL-37, IL-38, and VitD levels were evaluated in 90 women with GD and 93 control women using enzyme-linked immunosorbent assay kits. Depending on therapy, six patients were newly diagnosed (ND; untreated), and 50 patients were receiving only carbimazole (CMZ), while 34 patients were also on CMZ but also received one (31 patients), two (one patient), or three (two patients) doses of radioactive iodine (RAI).

Results: IL-37 levels were significantly higher in GD patients than in controls, while IL-38 and VitD levels were significantly decreased. As indicated by the area under the curve (AUC), receiver operating characteristic curve analysis demonstrated the potential of IL-37, IL-38, and VitD as biomarkers to distinguish GD patients from controls (AUC = 0.953, 0.959, and 0.793, respectively). Multinomial logistic regression analysis showed that altered levels of IL-37, IL-38, and VitD were most likely associated with the pathogenesis of GD. IL-37 was negatively correlated with IL-38 and VitD, while IL-38 and VitD were positively correlated.

Conclusion: Serum Il-37 levels were upregulated in women with GD, while IL-38 and VitD levels showed downregulated levels. The latter two were positively correlated while they showed a negative correlation with IL-37.

Keywords: Graves' disease; IL-37; IL-38; therapy; vitamin D.

FIGURE 1

Column bar graph of IL‐37 (A), IL‐38 (B) and vitamin D (C) levels in the serum of Graves' disease (GD) patients and controls (CTRL). Column represents median. Bar represents interquartile range (IQR). Significant differences between medians were assessed using Mann–Whitney U test (***p < 0.001). IL‐37 levels were significantly higher in GD patients than in CTRL (84.8 [IQR: 74.5–104.0] vs. 61.9 [IQR: 57.4–65.6] ng/L; p < 0.001). On the contrary, IL‐38 levels were significantly decreased in GD patients compared to CTRL (43.0 [IQR: 41.0–46.5] vs. 70.0 [IQR: 62.0–86.0] pg/ml; p < 0.001). Vitamin D levels were also significantly lower in GD patients than in CTRL (12.8 [IQR: 8.9–25.9] vs. 33.6 [21.9–45.0] ng/ml; p < 0.001).

FIGURE 2

Receiver operating characteristic (ROC) curve analysis of IL‐37 (A), IL‐38 (B) and vitamin D (C) levels in Graves' disease (GD) patients versus controls (CTRL). The analysis demonstrated the potential of IL‐37 (area under the curve [AUC] = 0.953; 95% confidence interval [CI] = 0.923–0.982; p < 0.001; cut‐off point = 67.9 ng/L; Youden index [YI] = 0.75; sensitivity = 87.1%; specificity = 87.8%), IL‐38 (AUC = 0.959; 95% CI = 0.928–0.990; p < 0.001; cut‐off point = 57.5 pg/ml; YI = 0.84; sensitivity = 91.4%; specificity = 92.2%) and vitamin D (AUC = 0.793; 95% CI = 0.730–0.857; p < 0.001; cut‐off point = > 24.0 ng/ml; YI = 0.44; sensitivity = 72.0%; specificity = 72.2%) as biomarkers to distinguish GD from CTRL.

FIGURE 3

Spearman's rank correlation analysis between IL‐37, IL‐38, and vitamin D levels among all participants (Graves' disease and controls) showing correlation coefficient (r _s). IL‐37 was negatively correlated with IL‐38 (r _s = −0.617; p < 0.001) and vitamin D (r _s = −0.424; p < 0.001), while IL‐38 and vitamin D were positively correlated (r _s = 0.367; p < 0.001).