IKZF1 rs4132601 and rs11978267 gene polymorphisms and paediatric systemic lupus erythematosus; relation to lupus nephritis.

The demographic factors, the socioeconomic status and the ethnicity of populations are important players that determine the incidence, the prevalence and the spectrum of systemic lupus erythematosus (SLE) clinical presentations in different populations. Therefore, the purpose of the present research was to investigate the possible association between the Ikaros family zinc finger 1 gene (IKZF1) rs4132601 and rs11978267 single nucleotide polymorphisms (SNPs) and SLE susceptibility and clinical presentations including lupus nephritis (LN) among Egyptian paediatric patients. After DNA extraction from Ethylenediaminetetraacetic acid (EDTA) blood samples for 104 paediatric SLE (pSLE) patients and 286 healthy controls, the investigated SNPs (IKZF1 rs4132601 and rs11978267) were genotyped using TaqMan-Real-time Polymerase chain reaction (PCR). The G allele, GG and GT genotypes of IKZF1 rs4132601 were associated with pSLE (pc<.001, OR 2.97, 3.2 and 2.25, respectively). The GG and GA haplotype were more frequent in pSLE patients than other haplotypes (pc<.001, OR 3.47 and pc = .004, OR = 2.8, respectively). The studied SNPs have no impact on the distinctive features of pSLE. The rs4132601 TG genotype was significantly associated with proliferative LN (pc = .03) The IKZF1 rs4132601 can be considered a risk factor for SLE in the cohort of Egyptian children. The TG genotype of the IKZF1 rs4132601 may predispose to proliferative LN.

ARID5B rs10821936 and rs10994982 gene polymorphisms and acute lymphoblastic leukemia: relation to disease susceptibility and outcome.

ARID5B rs10821936 and rs10994982 single nucleotide polymorphism (SNP) have been associated with the risk of acute lymphoblastic leukemia (ALL) in different ethnic populations. We investigated the association between the ARID5B rs10821936 C > T, rs10994982 A > G, and susceptibility to ALL in a cohort of Egyptian individuals and investigated their role in relation to disease outcome. Real-time PCR typing was done for ARID5B rs10821936 and rs10994982 SNPs for 128 pediatric ALL (pALL), 45 adult ALL (aALL), and 436 healthy controls. Significant risk associations were found between the C allele (p < 0.001, OR = 2.02), CC genotype (p < 0.001, OR = 2.72), CT genotype (p = 0.011, OR = 1.45) of ARID5B rs10821936 and pediatric ALL especially T-ALL and adult ALL (p < 0.05). The CA haplotype (C allele of rs10821936 + A allele of rs10994982) was associated with the risk of ALL either pediatric ALL or adult ALL (p < 0.001). In the studied Egyptian population, it can be concluded that the C allele, CC, and CT genotypes of ARID5B rs10821936 and the CA haplotype may be a susceptibility risk factor for pediatric and adult ALL. However, the SNPs of ARID5B rs10821936 and rs10994982 were not found to be strongly associated with ALL outcomes.

Serum Soluble Fibrinogen-Like Protein 2 Represents a Novel Biomarker for Differentiation Between Acute and Chronic Egyptian Hepatitis B Virus-Infected Patients.

Hepatitis B virus (HBV) infection is considered as one of the most serious public health problems worldwide including Egypt. Soluble fibrinogen-like protein 2 (sFGL2) is a well-known immunomodulator that is produced by the T cells and has a strong inhibitory effect on the proliferation of T cells and maturation of dendritic cells (DC). In the current study, serum levels of sFGL2 were assessed utilizing enzyme-linked immunosorbent assay (ELISA) technique among 20 acute HBV-infected patients, 55 chronic HBV-infected patients and 15 healthy individuals. In addition, serum levels of soluble FAS ligand (sFASL), soluble FAS receptor (sFAS) as well as interferon-γ (IFN-γ) were assessed and correlated to the levels of sFGL2. According to our results, serum levels of sFGL2 were significantly higher in the acute HBV-infected patients than in the chronic HBV-infected patients and healthy individuals. On the other hand, the serum levels of sFASL, sFAS and IFN-γ were significantly higher in the chronic than in acute HBV-infected patients. Also, serum sFGL2 levels were negatively correlated with the serum levels of sFASL, sFAS, IFN-γ and albumin as well as hemoglobin concentration. Furthermore, serum sFGL2 levels were positively correlated with the activities of ALT and AST and total bilirubin levels in serum. Thus, the current work highlights the possibility of utilizing serum sFGL2 level as a novel biomarker for the differentiation between acute and chronic Egyptian HBV-infected patients.

Correlation of Serum Soluble Fibrinogen-Like Protein 2 with Soluble FAS Ligand and Interferon Gamma in Egyptian Hepatitis C Virus-Infected Patients and Hepatocellular Carcinoma Patients.

Infection with hepatitis C virus (HCV) remains one of the serious human diseases worldwide, especially in Egypt, which can lead to cirrhosis or hepatocellular carcinoma (HCC). However, the exact molecular mechanism of HCC progress in HCV-infected patients remains unclear. Soluble fibrinogen-like protein 2 (sFGL2) is a modulator of the immune response that is secreted by T cells and inhibits maturation of dendritic cells and T cell proliferation. In the current study, serum sFGL2 levels were analyzed by enzyme-linked immunosorbent assay (ELISA) technique in 30 chronic HCV-infected patients (HCV group), 30 chronic HCV-infected patients with HCC (HCC group), and 12 healthy individuals (control group). Moreover, serum levels of soluble FAS ligand (sFASL) and interferon gamma (IFN-γ) were analyzed and correlated with sFGL2 levels. According to our results, serum sFGL2 levels were significantly elevated in all patients with chronic HCV infection. However, HCC patients showed lower sFGL2 levels than HCV-infected patients without HCC incidence. In addition, serum sFASL levels were significantly elevated in both HCV and HCC groups, whereas serum IFN-γ levels were only elevated in the HCC group. Interestingly, sFGL2 correlated positively with serum total bilirubin level and negatively with serum levels of sFASL, IFN-γ, and albumin in HCV and HCC groups. Thus, conclusively, sFGL2 level increases in Egyptian HCV-infected and HCC patients. Taken together, the current work may open future possibility of designing new treatment strategies for HCV infection targeting sFGL2 and its immunosuppressive effect.

GATA3 rs3824662 gene polymorphism as possible risk factor in a cohort of Egyptian patients with pediatric acute lymphoblastic leukemia and its prognostic impact.

To investigate the possible role of GATA3 rs3824662 polymorphism as risk factor for the development of acute lymphoblastic leukemia (ALL) in a cohort of Egyptian children and to evaluate its prognostic role. Typing of GATA3 rs3824662 polymorphism was done using real-time PCR for 116 patients with ALL and 273 healthy controls. The A allele and AA genotype were significantly higher in ALL patients (p = .015 and .016, respectively) especially B-ALL (p = .014 and .01, respectively). The AA genotype was associated with shorter disease free survival (DFS) in univariate (p = .017) and multivariate cox regression analysis (p = .028), increased incidence of relapse (p = .008) and poor prognosis (p = .028) in pediatric ALL. The GATA3 rs3824662 A allele and AA genotype may be risk factors for the development of pediatric ALL especially B-ALL in the studied cohort of Egyptian patients. The AA genotype is associated with shorter DSF, increased incidence of relapse and poor prognosis in pediatric ALL.