Interleukin-18, Interleukin-18 Gene Polymorphisms and Interleukin-18 Binding Protein in Children and Adolescents with Immune Thrombocytopenia

Abstract

Immune thrombocytopenia (ITP) is an autoimmune illness characterized by an aberrant T cell response, which is supported by autoreactive B cell growth and differentiation. IL-18 expression has been linked to a number of autoimmune and inflammatory illnesses. IL18BP is a protein that binds IL-18 with high affinity, suggesting a potential mechanism for regulating IL-18 activity. Corticosteroids may play a significant role in reversing the IL-18-IL18BP ratio by upregulating IL18BP. Objective: The aim was to study associations between IL-18 and two associated gene polymorphism sites -607 & -137 with incidence and response to therapy in patients with ITP. Patients and Methods: It is a case control study conducted on children and adolescents with ITP. A total of 55 patients with different stages of ITP (25 acute, 18 persistent & 12 chronic patients) were recruited with 30 age matched healthy controls. All patients were subjected to full history and physical examination. Laboratory investigations included serial blood counts, IL-18 and IL-18BP serum levels using enzyme linked immunosorbent assay (ELISA) and IL-18 gene polymorphisms using polymerase chain reaction (PCR). Results: At diagnosis the median platelet count was 16× 109/L (range 2-79) & eventually increased to a median of 190× 109/L after treatment. IL-18 level was significantly higher than that of control (P<0.001) & even after treatment. There was no significant difference between patient and control groups regarding the studied gene polymorphism sites -607 & -137. The mean IL-18 was still significantly elevated in all stages of ITP compared to control group & as well the drop after treatment. This was also observed in IL-18 BP which increased significantly after response to steroid therapy. However, it was observed that the decline in level of IL-18 as well as increment in IL-18 BP was the least in the patients tested during the acute phase. Mean IL-18 & IL-18 BP levels show no significant differences with gender, family history of ITP, mode of treatment or genotype. Conclusion: Among the studied IL-18 gene polymorphisms, no significant difference was detected among ITP patients or had a significant correlation with clinical or laboratory markers. Reversed IL-18/IL-18BP ratio is an important modulator in pathogenesis of ITP. Increasing levels of IL-18BP could have a significant role in treatment.