الفهرس 
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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. They create antiplatelet autoantibodies, which aid in platelet phagocytosis by macrophages, mostly in the spleen. Macrophages, being the principal antigen-presenting cell during ITP, aid in the maintenance of the auto-immune response. CD8+ T lymphocytes contribute to thrombocytopenia by promoting platelet death. Aside from the destruction of peripheral platelets, abnormal bone marrow production exacerbates thrombocytopenia due to an immune response against megakaryocyte.
Interleukin 18 (IL-18), a member of the IL-1 family, is produced by monocytes, macrophages, and dendritic cells. In conjunction with IL-12, IL-18 increases Th1 responses by boosting interferon (IFN)-production by T lymphocytes and natural killer cells. However, in the absence of IL-12, IL-18 can promote a type 2 response by increasing the production of IgE and Th2 cytokines such as IL-4 and IL-13. Because of the importance of the Th1/Th2 balance in immunological homeostasis, IL-18 expression has been linked to a number of autoimmune and inflammatory illnesses.
IL18 BP is a protein that binds IL-18 with high affinity, suggesting a potential mechanism for regulating IL-18 activity. Interferon gamma induces IL18 BP, resulting in a negative feedback loop. The IL-18 BP has been used safely in clinical trials.
Three single-nucleotide polymorphisms (SNPs) in the IL-18 gene promoter have been found at locations 656 G/T (rs1946519), 607 C/A (rs1946518), and 137 G/C (rs187238) relative to the transcriptional start site. Among them, the dysfunctions of 607 C/A and 137 G/C alleles can result in elevated IL-18 expression. These SNPs have been associated with or linked to many autoimmune diseases.
Glucocorticoids (GC) are universally accepted as the first-line treatment for ITP and it may also play a significant role in reversing the IL-18-IL18 BP ratio by upregulating IL-18 BP.
This study was carried out at the Hematology Clinic, Children’s Hospital, Ain Shams University Hospitals, during the period from March 2015 to March 2020 The study included 85 children (55 patients and 30 controls), 37 males (43.5%) and 48 females (56.5%).
Patients were divided into three groups according to duration of illness as follows:
1. group І: 25 patients with newly diagnosed (acute) immune thrombocytopenia who did not receive any treatment prior to enrollment (Duration of illness < 3 months since diagnosis)
2. group ІІ: 18 patients with persistent immune thrombocytopenia (Duration of illness between 3 - 12 months since diagnosis).
3. group ІІI: 12 patients with non-responsive chronic immune thrombocytopenia (Duration of illness > 12 months since diagnosis).
A group of 30 age& sex matched healthy controls were included.
Our study aimed as a 1st objective to measure the levels of IL-18 and Its BP in patients with ITP & controls, and to determine the possible association of two SNPs of IL-18 -607 A/C and -137 G/C polymorphisms with susceptibility to ITP. As a 2nd objective to determine the association between all these parameters, the duration of illness and clinical responses to corticosteroid.
Our study showed that:
A total of 55 patients with 30 age matched controls were recruited, of the 55 patients, 23.6 % had positive family of ITP. Most of the patients had mixed cutaneous & mucus membrane bleeding (64%).
At diagnosis the median platelet count was 16 (range 2-79) & eventually increased to a median of 190 after treatment. IL-18 level was significantly higher than that of control (P<0.001) & even after improvement with treatment, it was still significantly higher than the control. IL-18 and IL-18BP levels among patients and controls at diagnosis and after treatment are shown in Table 1.
There was no significant difference between patient and control groups regarding both gene polymorphism sites -607 & -137. For IL-18 gene polymorphism genotype -137 (GG) was almost equally detected in patients & control (NS) other genotypes similarly showed non-significant difference between patients & control group. This also applies to -607 (CC) with no significant difference. Figure 1(a &b) illustrates different gene polymorphisms among patients and controls.
Among different stages of disease, almost 20-28% of patients with any stage (acute, persistent or chronic) had positive family history of ITP. Most patients with different stages of the disease had cutaneous bleeding but patients with chronic ITP mostly presented additionally with mucus membrane bleeding (97%).
Regarding pharmacotherapy, oral steroids was the main line of treatment (67%) & only 2% of patients received no treatment. Steroids was significantly prescribed mainly for patients with chronic and persistent ITP while IVIG as monotherapy was only used in acute ITP & wasn’t primary choice for persistent & chronic ITP. It was also observed that the carriers of GC allele of IL-18 gene polymorphism genotype -137 significantly required steroid therapy.
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 treatment. 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. Table 2 shows IL-18 and IL-18 BP among different patients with different stages of the disease.
There was no correlation between age at onset or platelet count and IL-18 or IL-18 BP whether before or after treatment. In addition, mean IL-18 & IL-18 BP levels were not correlated with gender, family history of ITP, mode of treatment or genotype.