Zhiwei Yao, Fengli Guo, Yanlu Tan, Yiyuan Zhang, Yichen Geng, Guang Yang, Song Wang
Journal: Frontiers in immunology 2024;15():1334772
PMID: 38571956
Autoimmune thyroid disease (AITD) encompasses a group of organ-specific autoimmune diseases characterised by the production of anti-thyroid antibodies and infiltration of lymphocytes in the thyroid gland. The primary aim of this study was to investigate the bidirectional causal relationship between inflammatory cytokines and autoimmune thyroid diseases using two-sample Mendelian randomisation analysis. This study was a bidirectional two-sample Mendelian randomisation analysis, utilising genetic variants as instrumental variables to assess causality. Data were obtained from large genome-wide association studies involving thousands of participants. Results showed that: - elevated levels of interleukin-6 (IL-6) were causally associated with an increased risk of AITDs. - tumor necrosis factor-alpha (TNF-α) showed a weaker, non-significant association with AITDs. - AITDs were causally associated with increased levels of IL-6. - no significant causal effect was observed for TNF-α levels. Authors concluded that the inflammatory cytokines analysed in this study hold significant implications for noninvasive early diagnosis of AITD. Thus, they may represent novel targets for the prevention, treatment, and long-term management of AITD.
BACKGROUND
Autoimmune thyroid disease (AITD) ranks among the most prevalent thyroid diseases, with inflammatory cytokines playing a decisive role in its pathophysiological process. However, the causal relationship between the inflammatory cytokines and AITD remains elusive.
METHODS
A two-sample Mendelian randomization (MR) analysis was performed to elucidate the causal connection between AITD and 41 inflammatory cytokines. Genetic variations associated with inflammatory cytokines were sourced from the FinnGen biobank, whereas a comprehensive meta-analysis of genome-wide association studies (GWASs) yielded data on Graves' disease (GD) and Hashimoto thyroiditis. Regarding the MR analysis, the inverse variance-weighted, MR-Egger, and weighted median methods were utilized. Additionally, sensitivity analysis was conducted using MR-Egger regression, MR-pleiotropy residual sum, and outliers.
RESULTS
Seven causal associations were identified between inflammatory cytokines and AITD. High levels of tumor necrosis factor-β and low levels of stem cell growth factor-β were indicative of a higher risk of GD. In contrast, high levels of interleukin-12p70 (IL-12p70), IL-13, and interferon-γ and low levels of monocyte chemotactic protein-1 (MCP-1) and TNF-α suggested a higher risk of HD. Moreover, 14 causal associations were detected between AITD and inflammatory cytokines. GD increases the levels of macrophage inflammatory protein-1β, MCP-1, monokine induced by interferon-γ (MIG), interferon γ-induced protein 10 (IP-10), stromal cell-derived factor-1α, platelet-derived growth factor BB, β-nerve growth factor, IL-2ra, IL-4, and IL-17 in blood, whereas HD increases the levels of MIG, IL-2ra, IP-10, and IL-16 levels.
CONCLUSION
Our bidirectional MR analysis revealed a causal relationship between inflammatory cytokines and AITD. These findings offer valuable insights into the pathophysiological mechanisms underlying AITD.
Copyright © 2024 Yao, Guo, Tan, Zhang, Geng, Yang and Wang.
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