Immunology
DEEPTI SURI, MD
Professor of Allergy and Immunology
Post graduate institute of medical education and research
Chandigarh, Chandigarh, India
Background: Kawasaki Disease (KD) is an acute vasculitis with a special predilection to coronary artery aneurysms. Inflammasomes are large cytosolic multiprotein complexes that drive inflammation by Interleukin-1β [IL-1β]). There is a paucity of literature regarding the role of inflammasomes in the pathogenesis of KD. This study focuses on assessing various inflammasomes (NLRP3, NLRC4, NLRP12, NLRP1, and AIM2) and downstream molecules (PYCARD, CASP1, and IL1B) in KD patients.
Methods: This study was carried out in 25 patients diagnosed with KD during the study period January 2018- April 2023. Diagnosis of KD was based on AHA 2017 guidelines. All patients received intravenous immunoglobulin (IVIg) and aspirin. Blood samples were collected during the acute stage and then in the convalescent phase. Inflammasome expression was analyzed by Real time PCR in patients as well as controls. In addition we also enrolled patients from follow up clinic to perform Kompetitive allele-specific PCR (KASP). KASP was performed to study a Single Nucleotide Polymorphism (SNP) in the NLRP3 gene (Rs id 10754558) in 70 follow-up patients and 60 controls, and the odds ratio calculated to show the SNP's association with the disease.
Results: Results indicated an increase in NLRP3 mRNA expression in acute KD patients compared to convalescent phase (p=0.5512) and controls (p=0.350). AIM2 and NLRC4 also showed increased expression in acute KD patients compared to convalescent phase (p=0.1840 and p=0.3912, respectively). NLRP12 demonstrated a significant decrease in acute KD compared to controls (p=0.0329). Downstream molecules, such as PYCARD, showed increased levels (p < 0.999) in acute KD compared to convalescent KD. A non-significant increase was observed in CASPASE1 in acute KD (p < 0.999) compared to convalescent KD. IL1B expression also increased in acute KD (p < 0.999) compared to convalescent KD. The odds ratio for the SNP was more than 1 (1.66), indicating its association with the disease.
Conclusion: In conclusion, the increased expression of NLRP3, AIM2, NLRC4, PYCARD, CASP1, and IL1B in acute KD patients suggests the activation of the inflammasome pathway in KD pathogenesis. Blocking this pathway may offer a potential therapeutic target for KD.