Low serum interleukin‐38 levels in patients with Graves’ disease and Hashimoto’s thyroiditis

Xu, Jialu; Huang, Gailing; Weng, Linjie; Gong, Luping; Mao, Yu; Li, Yan; Li, Mingcai

doi:10.1002/jcla.24101

Cited by 13 publications

(13 citation statements)

References 32 publications

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“…Patients with atopic dermatitis ( 20 ), influenza ( 21 ), SLE ( 22 ), rheumatoid arthritis ( 25 , 39 ), myocardial infarction ( 23 ), sepsis ( 24 ), acquired immune-mediated neuropathies ( 31 ), osteoarthritis ( 32 ), acute respiratory distress syndrome ( 35 ), inflammatory bowel disease ( 33 ), type 2 diabetes ( 41 ), and vitiligo ( 43 ) present with higher blood concentrations of IL-38. This in contrast to e.g., patients with Graves’ and Hashimoto’s thyroiditis ( 44 ), Sjögren’s disease ( 34 ), Behçet’s disease ( 37 ), chronic brucellosis ( 40 ), and psoriasis ( 27 ), in whom IL-38 circulating concentrations were lower compared to healthy volunteers.…”

Section: Discussionmentioning

confidence: 72%

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Circulating interleukin-38 concentrations in healthy adults

Teufel

Graaf²,

Netea³

et al. 2022

Front. Immunol.

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Interleukin (IL)-38 is the latest discovered member of the interleukin-1 family, which has anti-inflammatory properties similar to IL-36Ra. Several studies compared circulating IL-38 concentrations in healthy and diseased populations to characterize its role in both auto-immune and inflammatory pathologies, with both higher and lower concentrations being associated with certain diseases. However, in order to use IL-38 as a biomarker, a reference range in healthy adults is needed. To establish a reference IL-38 circulating concentration, accessible data from 25 eligible studies with IL-38 concentrations in healthy adults was collected. To validate the values found in literature, we measured IL-38 concentrations by enzyme-linked immunosorbent assay (ELISA) in several cohorts from our own institute. Additionally, the effect of blood collection techniques, freeze thawing cycles, and hemolysis on IL-38 measurements was assessed. To evaluate the importance of the genetic background of individuals as confounding factor of IL-38 synthesis, we used publicly available eQTL databases with matched data on allele frequencies in individuals of different ethnicities. Mean IL-38 concentrations in the various studies were weighted by their corresponding sample size, resulting in a weighted mean, and weighted upper and lower limits were calculated by mean ± 2 SD. Differences of over 10.000-fold were found in the weighted means between studies, which could not be attributed to the blood collection method or assessment of IL-38 in plasma or serum. Although IL-38 concentrations were markedly higher in Chinese then in European population studies, we could not show an association with the genetic background. From our analysis, a reference range for circulating IL-38 in healthy adults could thus not yet be established.

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Section: Discussionmentioning

confidence: 72%

“…Between September 2015 and December 2021 25 published studies ( Table 2 ) fulfilled the inclusion criteria as described in the Methods section ( 20 – 44 ). In order to determine the distribution of the collected data an overview figure was made ( Figure 1A ).…”

Section: Resultsmentioning

confidence: 99%

Circulating interleukin-38 concentrations in healthy adults

Teufel

Graaf²,

Netea³

et al. 2022

Front. Immunol.

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“… 27 , 28 In GD, as in the current study, serum IL‐38 levels were significantly lower in patients than in CTRL, and the authors suggested that IL‐38 levels could be considered as a potential novel prognostic biomarker for GD. 12 Taken together, these findings suggest that IL‐38 may play roles in immune cell homeostasis with cytokine regulation as a mechanism involved in autoimmune diseases. Indeed, IL‐38 has been shown to be involved in regulating the differentiation and function of many immune cells, including T cells, PBMCs, macrophages, and dendritic cells, and thus may influence the development of autoimmune diseases.…”

Section: Discussionmentioning

confidence: 90%

“… 11 Regarding GD, a recent study demonstrated that IL‐38 levels were significantly lower in patients than in controls and suggested the potential of IL‐38 as a new diagnostic biomarker for the disease. 12 …”

Section: Introductionmentioning

confidence: 99%

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

Ibrahim

Sulaiman

Al-Shammaa³

et al. 2022

Clinical Laboratory Analysis

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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.

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“…Moreover, in osteoarthritis patients, higher IL-38 levels indicated severe disease activity [ 27 ]. In Graves’ disease and Hashimoto’s thyroiditis, two types of thyroid inflammatory diseases, low serum IL-38 levels were observed [ 28 ]. These results suggest that IL-38 may exhibit anti- or pro-inflammatory actions in different pathological states, similar to its family members [ 15 ].…”

Section: Discussionmentioning

confidence: 99%

Serum interleukin-38 levels correlated with insulin resistance, liver injury and lipids in non-alcoholic fatty liver disease

et al. 2022

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Background Insulin resistance, liver injury and dyslipidemia are reported in non-alcoholic fat liver disease (NAFLD) patients. Interleukin (IL)-38 may take part in the pathophysiology of insulin resistance. Nevertheless, the function of IL-38 in NAFLD is unknown. Herein, we determined whether serum IL-38 level might be utilised as a biochemical marker for diagnosing NAFLD. Methods NAFLD patients and healthy participants (n = 91 each) were enrolled. Circulating serum IL-38 levels were detected using enzyme-linked immunosorbent assay. Other metabolic and inflammatory indices related to NAFLD were also assessed. Results Patients with NAFLD had higher serum IL-38 levels than healthy individuals. Significantly higher serum IL-38 levels were found in patients with severe and moderate NAFLD than in patients with mild NAFLD. IL-38 showed a significant correlation with parameters of insulin resistance, inflammation, and liver enzyme in NAFLD cases. Anthropometric, insulin resistance, inflammatory parameters, lipids and frequency of NAFLD showed significant differences among the serum IL-38 level tertiles. Participants in the 2nd and 3rd tertiles of serum IL-38 levels had a greater risk of NAFLD than those in the 1st tertile. Furthermore, IL-38 ROC curve showed a high area under ROC with 0.861. Conclusions It is possible for serum IL-38 to be a biomarker for NAFLD.

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Low serum interleukin‐38 levels in patients with Graves’ disease and Hashimoto’s thyroiditis

Cited by 13 publications

References 32 publications

Circulating interleukin-38 concentrations in healthy adults

Circulating interleukin-38 concentrations in healthy adults

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

Serum interleukin-38 levels correlated with insulin resistance, liver injury and lipids in non-alcoholic fatty liver disease

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