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Circulating Inflammatory Factors and Bidirectional Mendelian Randomization Analysis in Patients with Kawasaki Disease
Muqing Niu1, Jinyong Pan2,3, Kui Wang4
1The First Affiliated Hospital of Shihezi University, Shihezi, Xinjiang, People's Republic of China.
Insights
This study investigated causal links between inflammation and Kawasaki disease (KD). Interleukin-2 and Interleukin-8 were found to be significantly associated with KD risk, suggesting potential therapeutic targets.
Area of Science:
- Immunology
- Genetics
- Cardiovascular Disease
Background:
- Kawasaki disease (KD), or mucocutaneous lymph node syndrome, is a systemic immune vasculitis with unknown causes.
- KD is frequently associated with the development of coronary artery disease.
- Understanding the interplay between inflammatory factors and KD is crucial for disease management.
Purpose of the Study:
- To investigate the causal relationships between circulating inflammatory factors and Kawasaki disease (KD) using a bidirectional Mendelian randomization (MR) approach.
- To identify specific inflammatory mediators that may causally influence KD risk.
- To explore potential therapeutic targets for KD by examining inflammatory pathways.
Main Methods:
- A two-way pooled Mendelian randomization (MR) analysis was performed.
- Genetic data for 41 circulating inflammatory regulators were obtained from genome-wide association studies (GWASs).
- Inverse-variance weighting (IVW) was the primary analysis method, with MR-Egger, weighted median, and MR-PRESSO used for sensitivity analyses.
Main Results:
- Forward MR analyses did not reveal significant causal links between inflammatory factors and KD.
- Reverse MR analyses indicated that interleukin-2 (IL-2) and interleukin-8 (IL-8) are significantly associated with an increased risk of KD.
- Borderline significant associations were noted for other factors including B_NGF, EOTAXIN, HGF, and IL_12_P70.
Conclusions:
- This bidirectional MR study underscores the role of specific circulating inflammatory modulators in Kawasaki disease (KD) pathogenesis.
- Interleukin-2 and Interleukin-8 emerge as key inflammatory factors potentially influencing KD risk.
- Findings provide insights into KD etiology and suggest potential targets for novel therapeutic strategies.
Background:
Kawasaki disease (KD), also known as mucocutaneous lymph node syndrome, is a systemic immune vasculitis with an unclear etiology. It is often complicated by coronary artery disease. This study uses bidirectional Mendelian randomization (MR) to investigate the interaction between KD and circulating inflammatory factors, providing insights into their causal relationships.
Methods:
We conducted a two-way pooled MR analysis to examine the causal links between 41 circulating inflammatory regulators and the risk of KD. Genetic data related to inflammation were sourced from three genome-wide association studies (GWASs) involving CRP, PCT, and cytokines, while KD data were derived from other studies. Inverse-variance weighting (IVW) was the primary MR method, with sensitivity analyses performed using MR‒Egger, weighted median, weighted mode, and MR-PRESSO to ensure robustness.
Results:
Forward MR analyses showed no significant relationship between inflammatory factors and KD outcomes. In contrast, reverse MR, with KD as the exposure factor, revealed that interleukin-2 (IL-2) and interleukin-8 (IL-8) were significantly associated with KD (IL-2: OR=1.0085, P=0.037; IL-8: OR=1.0099, P=0.014). Borderline significant associations were observed for factors such as B_NGF, EOTAXIN, HGF, and IL_12_P70 in MR‒Egger and weighted median analyses.
Conclusion:
This bidirectional MR study highlights the role of circulating inflammatory modulators in KD risk, offering insights into KD pathogenesis and potential therapeutic targets.
