Association between ATP binding cassette gene member 1 polymorphism and glucocorticoid response in children with immune thrombocytopenia.

ATP binding Cassette gene member 1 (ABCB1) polymorphism has been incriminated in susceptibility to many malignant, infectious and autoimmune diseases. Recently, it was reported that ABCB1 polymorphisms might have a link to disease progression as well as response to therapy. We aimed to study the association between ABCB1 gene polymorphism and glucocorticoid response in children with newly diagnosed immune thrombocytopenia (ITP). A case control study was conducted on 90 newly diagnosed children with ITP and 90 healthy controls over a period of 1 year. ABCB1 (C3435T) polymorphism was determined by restriction fragment length polymorphism-polymerase chain reaction (RFLP-PCR) in patients and controls. There was no significant difference between patients and controls as regards to frequency of different ABCB1 genotypes (CC, CT, and TT genotypes were 44.4%, 36.7%, and 18.9% respectively in patients and 48.9%, 38.9%, and 12.2% respectively in controls, P value = 0.18). 80% of patients who received steroids alone or steroids in combination with intravenous immunoglobulin showed complete recovery. There was highly significant relationship between ABCB1 genotypes and response to steroids where 55 % of responders had CC (wild) genotype while 40 % of nonresponders had TT (mutant) genotype. We concluded that ABCB1 gene polymorphism may contribute to the response to steroids in Egyptian children with ITP where patients with homozygous CC genotype responded better to steroids than patients with homozygous TT genotype. These results may help us choose the appropriate initial treatment in these children.

Contribution of interleukin 27 serum level to pathogenesis and prognosis in children with immune thrombocytopenia.

ABSTRACT: Concepts surrounding the mechanisms of thrombocytopenia in ITP have shifted from the traditional view of autoantibody mediated platelet destruction to more complex mechanisms in which impaired platelet production, T-cell-mediated effects, and disturbed cytokine profiles play a role. Interleukin 27 (IL-27) plays pleiotropic roles in immunomodulation and autoimmune diseases.We aimed to determine the level of IL-27 in patients with ITP and its relationship to patient and disease characteristics as well as disease chronicity and response to treatment.Sixty childrens with primary immune thrombocytopenia were consequetively enrolled in this study as well as 20 age and sex matched healthy controls.ITP patients had significantly higher levels of IL-27 than controls (770.6 and 373.8 pg/ml, respectively). Patients with acute ITP had the highest levels of IL-27 among patient groups, while patients in remission had the lowest IL-27 levels (860.1and 622.9 pg/ml, respectively). Patients who received IVIG and combined steroids plus IVIG had significantly higher IL-27 levels than others. Patients who received Eltrombopag had significantly lower IL-27 levels than others.IL-27 seems to play a role in pathogenesis of childhood ITP. IL-27 can be used as a predictor for disease occurrence as well as responsiveness to treatment.

Role of serum cystatin C in the prediction of acute kidney injury following pediatric cardiac surgeries: A single center experience.

Intense contemporary research is directed towards validating novel biomarkers to predict acute kidney injury (AKI) in children undergoing cardiothoracic surgeries. We aimed to evaluate the role of cystatin C in early prediction of AKI following cardiac surgery in children with congenital heart disease. Prospective observational cohort study was conducted on 40 children with congenital heart disease undergoing cardiac surgery. 40 healthy children with matched age and sex were enrolled as a control group. Children were subjected to physical examination, routine blood tests, echocardiography, and measurement of plasma cystatin C level on different occasions. The median age of the patients was 3.65 years, a range from 1 to 5 years with no significant difference regarding the age and sex of cases and control groups. The mean serum cystatin C level in patients was 0.75 ±â€…0.15, 1.35 ±â€…0.34 and 1.21 ±â€…0.38 mg/dL (preoperative, at 6 h and at 24 h postoperative, respectively) with statistically significant difference P < .05. 30% of the patients developed postoperative AKI with significantly higher serum cystatin C at 6 hours postoperative >1.33 mg/dL compared to preoperative level p P < .05. Serum cystatin C level was positively correlated with cardiac bypass time, ischemic time and length of hospital stay at 6 hours postoperative. Serum cystatin C is a sensitive marker for early detection of AKI following cardiac surgery in children with congenital heart disease and it was positively correlated with cardiac bypass time, ischemic time and length of hospital stay.

PTPN22 gene polymorphism as a genetic risk factor for primary immune thrombocytopenia in Egyptian children.

OBJECTIVES: Several genetic and non-genetic risk factors are implicated in the etiology and pathogenesis of primary immune thrombocytopenia (ITP). Protein tyrosine phosphatase non-receptor 22 gene (PTPN22) plays an important role in regulation of signal transduction through the T-cell receptors. PTPN22 1858 C > T single nucleotide polymorphism was reported to be associated with increased risk of autoimmune diseases. There are very few studies investigating the role of PTPN22(SNP) 1858 C > T in childhood ITP. METHODS: This case-control study was designed for assessing the contribution of PTPN22 1858 C > T polymorphism to the risk of ITP in Egyptian children. Eighty children with newly diagnosed ITP were recruited from pediatric hematology out-patient clinic. Also, eighty age and sex-matched healthy children were enrolled as a control group. PTPN22 1858 C/T SNP gene polymorphism was performed using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). RESULTS: Frequency of PTPN22 1858 C/T genotypes CT, CC, and TT were 32.5,55, and 12.5% in patients versus 10, 90, and 0% in controls (p < 0.05).TT genotype was significantly associated with higher risk of ITP (OR = 17.8(0.94-333.35), 95% CI, and P = 0.02). CONCLUSION: PTPN22 gene polymorphism may play a pivotal role in genetic predisposition to ITP and disease progress in Egyptian children.

Tissue factor expression predicts outcome in children with neuroblastoma: A retrospective study.

Previous studies have revealed that the processes of tumor angiogenesis, metastasis and invasiveness are highly dependent on components of the blood coagulation cascade. Tissue factor (TF) is one of the key proteins in coagulation. Cumulative evidence suggested that in addition to its role in coagulation, TF regulates intracellular signaling pathways that serve an important role in angiogenesis, tumor development and metastasis. In the present study, TF expression in neuroblastoma as well as its association with tumor stage, pathology and outcome were assessed. A total of 40 formalin-fixed paraffin-embedded tissues were evaluated for TF expression by immunohistochemical analysis. Results revealed that TF expression was positive in 75% of the analyzed tumor tissues. No significant association between TF expression and sex, age, tumor stage or disease pathology was observed. MYCN proto-oncogene bHLH transcription factor (MYCN) was upregulated in 45% (n=18) of the study cases. Positive TF expression was observed in 94.4% of patients (n=17) with upregulated MYCN, while 59% of patients (n=13) with normal MYCN showed positive TF expression (P<0.05). TF expression was a significant outcome predictor for patients; 18/30 patients (60%) with positive TF expression succumbed to the disease during the study period. In conclusion, TF may be a promising prognosis indicator for neuroblastoma. Future studies to determine how TF affects the progression and outcome of neuroblastoma, as well as to investigate its potential role as a therapeutic target, are required.

Association between genotype and disease complications in Egyptian patients with beta thalassemia: A Cross-sectional study.

In beta thalassemia, the degree of globin chain imbalance is determined by the nature of the mutation of the ß-gene. ß° refers to the complete absence of production of ß-globin on the affected allele. ß+ refers to alleles with some residual production of ß-globin. The homozygous state results in severe anemia that necessitates regular blood transfusion. On the other hand, frequent blood transfusion can lead to iron overload resulting in progressive dysfunction of the heart, Liver as well as multiple endocrinopathies. We studied the impact of genotype on the development of disease complications in patients with ß thalassemia. A Cross sectional study was carried on 73 patients with beta thalassemia. Genotyping was determined by DNA sequencing technique. Routine investigations as well as MRI liver and heart were performed to assess iron overload. We found that ß+ß+ was the most common genotype in our patients followed by ß°ß° and ß°ß+. Mean Liver iron content (LIC) was significantly higher in ß°ß° compared to ß°ß+ and ß+ß+ genotypes and mean cardiac T2* was significantly lower in ß°ß° compared to ß°ß+ and ß+ß+ genotypes. Hepatic complications, hepatitis C, cardiac complications and some endocrinopathies were significantly higher in patients with ß°ß° genotype compared to other genotypes which explain the role of the underlying genetic defect in thalassemia patients in development of disease complications.

Association of IL-10 gene polymorphisms and susceptibility to Juvenile Idiopathic Arthritis in Egyptian children and adolescents: a case-control study.

BACKGROUND: Juvenile Idiopathic Arthritis (JIA) is the most common chronic arthritis in children worldwide. Among anti-inflammatory cytokines, interleukin-10 (IL-10) is a key immunosuppressive cytokine involved in the pathogenesis of JIA. To date, only a few studies concerned the association of interleukin-10 gene polymorphisms with JIA. In this study, we aimed to investigate 3 cytokine single-nucleotide polymorphisms situated at positions -1082(G/A), -819(C/T), and -592(C/A) in the promoter region of the IL-10 gene to determine whether this polymorphism could be a marker of susceptibility to JIA in Egyptian children and adolescents. We also measured the serum level of IL-10 to assess its relation to such polymorphism. METHODS: This was a case-control study included 100 patients diagnosed with JIA, and matched with age, gender, ethnicity 100 healthy control subjects. Interleukin-10 -1082(G/A), -819(C/T), and -592(C/A) polymorphisms were genotyped by amplification refractory mutation system- polymerase chain reaction (ARMS)-PCR methodology, while the serum IL10 levels were measured by ELISA method. RESULTS: Compared to the controls subjects, the frequency of IL-10- AA genotype and A allele at the -1082 position were overrepresented in patients with JIA (OR = 2.7; 95% CI: 1.1-6.4 for the AA genotype; P <0.05 and OR: 1.5; 95% CI: 1.03-2.3 for the A allele; P <0.05 respectively). On the other hand, no significant differences were found between the 2 groups in the genotype or allele frequencies for the -819 and -592 positions. Of note, we found a significant positive association between the IL-10 (-1082) AA genotype and susceptibility to polyarticular JIA (OR: 4.3; 95% CI: 1.5-12.7; P <0.01). We observed that patients with the IL-10 (-1082) AA genotype had significantly lower serum IL-10 levels (2.3 ± 0.9 pg/ml) compared to those with AG genotype (7.6 ± 1.5 pg/ml) and GG genotype (9.5 ± 1.2 pg/ml); P < 0.01, respectively. CONCLUSION: We demonstrate for the first time, to the best of our knowledge, that the presence of an A allele or AA gene variant at the -1082 position of the promoter region of the interleukin-10 gene may constitute risk factors for developing JIA in Egyptian children and adolescents. Moreover, we observed a significant positive association between the IL10 -1082 AA gene variant and susceptibility to polyarticular JIA.

Oral magnesium supplementation improves glycemic control and lipid profile in children with type 1 diabetes and hypomagnesaemia.

Dietary supplementation with magnesium (Mg) in addition to classical therapies for diabetes may help in prevention or delaying of diabetic complications.We aimed to evaluate the status of serum Mg in children with type 1 diabetes and assessing its relationship to glycemic control and lipid profile. Then evaluating the effect of oral Mg supplementation on glycemic control and lipid parameters.We included 71 children at Pediatric Endocrinology Outpatient Clinic, Zagazig University, Egypt with type 1 diabetes and assessed HBA1c, lipid profile, and serum Mg at the start of study. Patients with serum Mg level < 1.7 mg/dL were given 300 mg Mg oxide for 3 months. After that we reevaluated HBA1c, lipid profile, and serum Mg in all patients.The study included 71 patients with type 1 diabetes (32 males and 39 females); their mean age was 9.68 ±â€Š3.99 years. The mean serum Mg level was 1.83 ±â€Š.27 mg/dL. Hypomagnesemia was detected in 28.2% study patients. Serum Mg was found to be positively correlated with high density lipoprotein, mean corpuscular volume and platelet count (P < 0.001), and negatively correlated with age, HbA1c, triglycerides, total cholesterol, low density lipoprotein, and duration of diabetes (P < 0.001). There was significant reduction in HBA1c in group given Mg supplementation. HBA1c was initially 10.11% ±â€Š0.87%. After 3 months of oral Mg supplementation it is reduced to 7.88% ±â€Š0.42% (P < 0.001). There was statistically significant difference in lipid parameters in hypomagnesemic diabetic patients before and after Mg supplementation with significant reduction in serum triglycerides, LDL, and total cholesterol following Mg supplementation with P < 0.001. Although HDL shows a significant increase after Mg supplementation in hypomagnesemic diabetic children with P < 0.001.Correction of hypomagnesemia in type 1 diabetic children with oral Mg supplements is associated with optimization of glycemic control and reduction of atherogenic lipid fraction as well as increase in protective lipid fraction.

Interleukin-1ß and interleukin-1receptor antagonist polymorphisms in Egyptian children with febrile seizures: A case-control study.

Febrile seizure is the most common seizure disorder of childhood. Of the pro-inflammatory cytokines, interleukin-1 is defined as the first endogenous pyrogen.We designed this study to investigate single-nucleotide polymorphisms (SNPs) situated at positions -31 (C/T), and -511 (C/T) of interleukin-1beta (IL-1ß) gene promoter and interleukin-1receptor antagonist (IL-1RA) gene variable number of tandem repeats in intron 2 (VNTR); to determine whether these polymorphisms could be a marker of susceptibility to febrile seizures in Egyptian children and we also measured the serum level of IL-1ß to assess its relation to such polymorphisms.This was a case-control study included 155 patients with febrile seizure, and matched with age, sex, ethnicity 155 healthy control subjects. IL-1ß promoter at positions -31 (C/T), -511 (C/T), and IL-1RA gene VNTR polymorphisms were genotyped by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP), while the serum IL-1ß levels were measured by enzyme-linked immunosorbent assay (ELISA) method.The frequency of the IL-1ß-511 TT genotype and T allele at the same position were observed to be increased in patients with febrile seizures (FS) compared with the control group (odds ratio [OR]: 3.96; 95% confidence interval [CI]: 1.68-9.5; P = 0.001 for the TT genotype and OR: 1.65; 95% CI: 1.18-2.3; P = 0.003 for the T allele, respectively). The IL-1 RA II/II homozygous variant and IL-1 RA allele II were overrepresented in patients with FS than control group (OR: 4.02; 95% CI: 1.78-9.15; P = 0.001and OR: 1.73; 95% CI: 1.24-2.4; P = 0.001, respectively). We found a significant positive association between the IL-1 RA II/II genotype and susceptibility to FS in sporadic cases as did allele II at the same position (OR: 5.04; 95% CI: 2.1-12.5 for the IL-1 RA II/II genotype; P = 0.001) and (OR: 1.94; 95% CI: 1.3-2.8 for the allele II; P = 0.001, respectively). Carriers of the IL-1RA II/II homozygous variant and allele II had significantly higher serum levels of IL-1ß compared with those with other genotypes and alleles.We demonstrate for the first time that the presence of a T allele or TT genotype at -511 of IL-1ß promoter and IL-1RA II/II genotype constitute risk factors for developing FS in Egyptian children.

Impact of iron deficiency anemia on the function of the immune system in children.

The importance of iron deficiency as a public health problem is based ultimately on the seriousness of its consequences on health. The most extensively investigated consequences of iron deficiency involve work performance and immune function. The significance of the effects on work performance is generally accepted. In contrast, data on the influence of iron deficiency on immune function are often perceived as being confusing and contradictory.We aimed to evaluate the effect of iron deficiency anemia on humoral, cellular, nonspecific immunity, and also the effect on the cytokines that are the key factors of many immunologic steps.Forty children with iron deficiency anemia and 20 age and sex-matched healthy children were included. All children were subjected to full medical history, thorough clinical examination, complete blood count, iron indices (serum iron, serum total iron-binding capacity, serum ferritin, and transferrin saturation), immunoglobulin assay (IgA, IgG, and IgM), interleukin (IL)-6 serum level, study of T-lymphocyte subsets, and evaluation of phagocytic function of macrophages and oxidative burst activity of neutrophils.Patients had significantly lower IgG levels, IL-6, phagocytic activity, and oxidative burst of neutrophils than controls, although there was no significant difference between patients and controls with regard to other immunoglobulins and CD4/CD8 ratio. There was significantly positive correlation between serum iron and IL-6 serum level.We concluded that humoral, nonspecific immunity (phagocytic activity and oxidative burst), and the IL-6 are influenced in patients with iron deficiency anemia. Study of these abnormalities after correction of iron deficiency is strongly needed.

Effect of breastfeeding versus infant formula on iron status of infants with beta thalassemia major.

BACKGROUND: Thalassemia major or Cooley's anemia is the most severe form of beta thalassemia in which the complete lack of beta protein in the hemoglobin causes a life-threatening anemia requiring regular blood transfusions and extensive ongoing medical care. These extensive, lifelong blood transfusions lead to iron-overload that must be treated with chelation therapy to prevent early death from organ failure. We compared serum iron and ferritin levels amongst infants aged up to one year with beta thalassemia major according to their feeding types, including exclusively breastfed, exclusively formula fed and combined (both breast and formula) fed types. METHODS: Sixty out of 176 screened infants with transfusion dependant beta thalassemia major were recruited from the outpatient clinic of thalassemia at Zagazig University Hospital in Egypt, between 2007 and 2014. Patients were classified into three groups (20 patients per group) according to type of feeding. Group 1: exclusive breastfeeding, around 6-8 feeds per day; group 2: exclusive infant formula feeding, 120-150 ml of formula per kilogram of body weight per day divided into 6-8 feeds and group 3: combined breastfeeding and formula per day. RESULTS: Serum iron and ferritin levels were lower in group 1 compared to groups 2 and 3. The mean serum iron for group 1 was 73, 87 and 96 ug/dl at 6, 9 and 12 months respectively, while that for group 2 was 85, 99 and 112 ug/dl at 6, 9 and 12 months respectively and for group 3 was 78, 92 and 99 ug/dl at 6, 9 and 12 months respectively. The mean serum ferritin for group 1 was 283, 327 and 497 ng/ml at 6, 9 and 12 months respectively, while that for group 2 was 310, 389 and 591 ng/ml at 6, 9 and 12 months respectively and for group 3 was 291, 345 and 515 ng/ml at 6, 9 and 12 months respectively. The differences were not statistically significant. CONCLUSIONS: Breastfed infants with beta thalassemia major may accumulate less iron than infants fed iron fortified formula anticipating later onset of iron overload in the breastfed infants. Larger studies are needed to support these findings.