Cytokine Gene Polymorphism in Childhood Immune Thrombocytopenic Purpura (ITP) and Response to Different Treatment Modalities

Abstract

Immune thrombocytopenic purpura (ITP) is an autoimmune disease characterized by increased platelet destruction. Although the cause of ITP remains unclear, it is accepted that both environmental and genetic factors play an important role in the development of the disease. In the present study, we aimed to detect characterization of the different cytokine gene polymorphisms, in childhood ITP patients. Also, to study the potential role of these polymorphisms in relation to chronicity and response to different treatment modalities. This study was conducted at Pediatric Hematology Clinic, Children Hospital, Ain Shams University in the period from March 2012 to September 2013 on Childhood ITP patients. The study group included 50 ITP cases that were classified into 20 newly diagnosed and 30 chronic ITP patients. Gender and age distribution among the 20 newly diagnosed ITP subgroup patients was11 males representing (55%) and nine females representing (45%) with a mean age was (3.26±2.47) years while among the 30 chronic ITP subgroup patients, (11) males representing (36.67%) and (19) females representing (63.33%) with a mean age of (8.98±3.58) years. A group of 50 healthy subjects of comparable age and sex were enrolled as a control group. All patients were subjected to detailed history taking, clinical evaluation, and laboratory investigations including complete blood count, and viral markers when indicated as well as analyzing polymorphisms of TNF-alpha, IL10, IL6, IL17&IL1A genes. In the present study we found that GC genotype of IL6 (-174), GA genotype of IL-10 (-1082) and GG genotype of TNF-α (−308), were the most prevalent among all enrolled ITP cases and also healthy controls is representing (56%, 50% and 58% respectively) among ITP cases and representing (82%, 76% and 90% respectively) among healthy controls. In contrary, CC genotype of IL-17F and A1A2 genotype of IL-1RaVNTR were the most prevalent among all enrolled ITP cases representing (78% and 48% respectively)while CT genotype of IL-17F and A1A1genotype of IL-1RaVNTR were the most prevalent among healthy controls representing (94% and 72% respectively). We also found that no one had TT genotype of IL17F among cases nor controls. There were significant differences between all ITP cases and controls in terms of CC genotype (p= 0.0001) & C allele (P=0.022) of IL-6, GG genotype (p= 0.029) of IL-10 (-1082), GA genotype (p= 0.001) of TNF-α (−308), A1A2 genotype (p= 0.039) & A2 allele (P<0.001) of IL-1RaVNTR and CC genotype(p= 0.0001) & C allele (P<0.001) of IL-17F. However we did not demonstrate significant difference between severity of disease according to initial bleeding score, life threatening bleeding and the studied cytokine gene polymorphism among all ITP cases. Comparing distribution of studied inflammatory cytokine gene frequencies among newly diagnosed and chronic ITP patients, we detected a significant difference in IL10 genotype distributions among both groups of ITP patients (P=0.042). AA genotype and A allele of IL10 were the highest distribution among newly diagnosed ITP patients while GA genotype and G allele were the highest distribution among chronic ITP patients representing 45%, 62.5 %, 60%&56.67% respectively. Also we detected a significant difference in both IL-1Ra genotype and allele distributions among both groups of ITP patients (P=0.001 and 0.003 respectively). A1A2 genotype and A1 allele of IL-1Ra were the highest distribution among newly diagnosed ITP patients representing 75% and 52.5% respectively, while A1A1 and A1 allele were the highest distribution among chronic ITP patients representing 66.67% &81.67% respectively. However no significant association between newly diagnosed or chronic ITP patients regarding IL6, TNF-α and IL17F polymorphism were noted.