Assessment of type I interferon-associated gene expression in patients diagnosed with Henoch-Schönlein purpura and Kawasaki disease

Aim: Vasculitis is a general term denoting changes in the vessel wall and related clinical conditions resulting from an inflammatory process. Henoch-Schönlein purpura (HSP) and Kawasaki disease (KD) are the most common types of childhood vasculitis. Although various factors such as viral infections, genetic factors, and environmental factors are implicated in the pathogenesis of both diseases, their pathogenesis remains unclear. The interferon signature, which reflects the activation of type I interferon pathways, is a diagnostic and prognostic tool that is significantly associated with the pathogenesis and management of autoimmune conditions. Understanding the pathogenesis of Henoch-Schönlein purpura and Kawasaki disease is crucial for developing effective treatment strategies. In our study, we aimed to evaluate the role of the interferon signature measured in patients diagnosed with Henoch-Schönlein purpura and Kawasaki disease compared to that in healthy individuals. Materials and Methods: Thirty-two patients diagnosed with Henoch-Schönlein purpura and four patients diagnosed with Kawasaki disease who presented to the Istanbul University-Cerrahpaşa, Cerrahpaşa Faculty of Medicine, Department of Pediatrics, Pediatric Rheumatology, General Outpatient Clinic, and Pediatric Emergency Outpatient Clinic between December 12, 2022, and March 1, 2024, and 45 age- and sex-matched healthy children were included in our study. Serum levels of IL-1, IL-6, IL-8, IL-10, IL-17, IL-18, TNF-α, TNF-R1, TNF-R2, and IFN-gamma were studied in serum samples obtained from all participants, and the expression of interferon-related genes (STAT1, IFI27, IFI44, IFI44L, IFIT1, and RSAD2) was studied in blood samples collected in ethylenediaminetetraacetic acid (EDTA)-coated tubes using the RT-PCR method. Results: Significant increases in the expression of three genes (IFIT1, IFI44, and IFI27) and decreased expression of the other three genes (RSAD2, STAT1, and IFI44L) were observed in patients diagnosed with HSP and KD compared to those in the control group. When evaluating the interferon scores of patients diagnosed with HSP, X significantly higher interferon scores were found in patients with gastrointestinal involvement, those requiring corticosteroid therapy, and those requiring hospitalization. No significant difference was found in interferon scores between patients with and without renal involvement. When evaluating the serum cytokine levels of patients diagnosed with HSP, significantly higher serum IL-1 levels were found in patients with gastrointestinal symptoms than in those without. When evaluating the interferon score of patients with Kawasaki disease, high interferon scores were found in three of four patients. Conclusion: Significant increases in the expression of interferon-related genes (IFIT1, IFI44, and IFI27) and significant decreases in the expression of interferon-related genes (RSAD2, STAT1, and IFI44L) were observed in patients diagnosed with Henoch-Schönlein purpura and Kawasaki disease compared to the control group. This may indicate dysregulation of the type 1 interferon pathway in the patient group. In patients diagnosed with HSP and with high interferon scores, a significantly increased risk of gastrointestinal involvement, corticosteroid therapy requirement, and hospitalization was observed. This reinforces the idea that the interferon score could serve as a crucial prognostic indicator.