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Abstract Immune thrombocytopenia is an autoimmune disorder caused by antiplatelet antibodies resulting from various etiologies that is characterized by increased platelet destruction and impaired production leading to a decrease in the platelet count. It is the most common cause of acquired thrombocytopenia in children of any age but with a peak occurrence between 2 and 5 years of age. According to the latest guidelines from American Society of Hematology, ITP is clinically classified into three types newly diagnosed (for all cases at diagnosis), persistent (for cases with ITP lasting between 3– 12 mo from diagnosis, spontaneous remission not achieved after the removal of treatment in between 3–12 mo from diagnosis), and chronic ITP (lasting for more than 12 mo) Immune thrombocytopenia is caused by autoantibodies against glycoproteins (GP) IIb/IIIa and GPIb/IX found in the platelet membrane. Interleukin-1B and Interleukin -1 Receptor antagonist are found on chromosome 2q14. IL-1 beta (IL-1β) is a proinflammatory cytokine released by macrophages in systemic inflammatory responses and regulates inflammatory reactions and immune responses by promoting cytokines such as IL-6 and IL-12 Genetic polymorphism of the cytokine genes is known to be linked with ITP etiopathogenesis. In addition, the majority of the autoimmune diseases including ITP are linked with abnormal functioning of T cells and cytokines as they contribute significantly to disease pathogenesis and Cytokines are not only associated with etiogenesis but also associated with severity and chronicity of immumne thrombocytopenia Summary 102 The aim of this work was to study the association between Interleukin-1B and Interleukin-1 receptor antagonist gene polymorphisms development and severity of primary immune thrombocytopenia in children. Our study was performed on 50 pediatric patients who are diagnosed as ITP and on treatment and follow up in the Hematology and Oncology Unit of the Pediatric department at Menoufia University Hospitals. The study was done over the period from August 2022 to September 2023. Also, the study included 50 healthy children with matched age and sex as a control group. All patients were subjected to the following after taking informed consent: 1. Detailed history taking. 2. Full clinical examination. 3. Hematological investigation including CBC and platelet indices. 4. Genetic molecular study: A- Examination of Interleukin -1 Receptor antagonist by variable time number repeats (VTNR) method. B- Genotyping of Interleukin -1B rs16944 polymorphism by real time PCR Results showed that: 1. Almost all cases presented with skin bleeding (100%), followed by oral bleeding (92%), while only 8% presented with epistaxis. 2. The clinical grade of overall bleeding was moderate degree (grade 3) in most of the cases (92%) 3. There was significant difference between patients and control regarding platelet count as it was decreased in patients as well as between studied periods (at presentation, at 7 days and at 1 month). Summary 103 4. Regarding plateletcrit, there was significant difference between patients and control as well as at different periods in patients as it was decreased at 1 month more than at presentation and at 7 days. 5. Almost all cases (98%) received steroids treatment, the majority (80%) responds to prednisolone. Also, thrombopoietin receptor agonist (TPO-RA) was used in 76%, IVIG in 12% while no cases received Anti –Rh D treatment 6. There was a significant increase of rs16944 of IL1B mutant homozygous GG genotype and mutant G allele in cases than in control group with p value (<0.001). Also, ITP cases have risk of about 4.6 times more higher than control to carry mutant allele. 7. ITP cases presented with overall moderate to severe (grade 3-4) bleeding are significantly associated with increase of heterozygous AG (22/50) and mutant homozygous GG (18/50) genotype compared with cases carrying wild homozygous AA (8/50), Also, all cases presented with epistaxis (1-4) carried the mutant homozygous (GG) genotype of rs16944 of IL1B polymorphism. 8. There was a significant increase of heterozygous and mutant homozygous genotypes and mutant II allele of IL-1R antagonist polymorphism in cases than in control group with p value (<0.001), Moreover ITP cases have risk of about 6.3 times more than control to carrying the mutant allele than healthy children. 9. ITP cases presented with epistaxis (grade 1-4) are significantly associated with increase of mutant homozygous (II/II) genotype of IL- 1RA polymorphism. |