Clusterin in atopic and non-atopic childhood asthma.

Several biomarkers have been studied to diagnose or to detect the phenotype of asthma. Clusterin is a sensitive cellular biosensor of oxidative stress and has been studied as a biomarker for inflammatory diseases. We aimed to study serum clusterin level in atopic versus non-atopic childhood asthma and its relation to disease severity. This case-control study included 160 children; 120 stable asthmatic children and 40 apparently healthy children. Asthmatic children were further subdivided into atopic and non-atopic. All children were subjected to medical history taking, clinical examination, and laboratory investigations including complete blood count, serum IgE, serum clusterin level and spirometry before and after bronchodilator therapy. In comparison to controls, patients had significantly higher eosinophils count which was higher in atopic than non-atopic group, also serum IgE level was higher in the atopic asthmatics (118.1 ± 16.2 U/ml) than in both the non-atopic asthmatics (81.2 ± 6.1 U/ml) and the controls (76.3 ± 11.6 U/ml). There was statistical significant difference in serum levels of Clusterin which were highest in the atopic group (182.5 ± 33.5 ng/l), followed by the non-atopic patients (127.5 ± 32.5 ng/l) and lowest in the controls (46.09 ± 7.01 ng/l). Moreover, the higher the severity of asthma, the higher was the level of serum clusterin. In conclusion serum level of clusterin was higher in atopic than non-atopic asthmatic children and it increases significantly with increased severity of the disease.

Assessment of IL-17F rs763780 gene polymorphism in immune thrombocytopenia.

Interleukin-17F rs763780 (7488A/G) gene polymorphism obviously affecting the expression and activity of IL17F and may affect primary immune thrombocytopenia (PIT) susceptibility and its clinical features in Egyptian children and adults. 105 ITP patients divided into (63 pediatric and 42 adult patient) and 112 age and sex matched healthy controls were enrolled in this case control study. All patients were subjected to history taking; clinical examination, CBC, bone marrow aspiration and genotyping of IL17F rs763780 polymorphism by (PCR-RFLP) technique. Our results revealed significant decrease in the mutant heterozygous genotype AG and also in IL-17F mutant allele G frequency in ITP patient group and associated with increased risk for ITP compared with the control group (P = 0.04 and P = 0.005 respectively). Furthermore, the mutant allele G frequency was significantly decreased in childhood onset than adult onset ITP (OR = 0.31, P = 0.02) and also was significantly lower in chronic ITP when compared with newly diagnosed and persistent ITP (P = 0.005). Patients with the AA genotype showed severe thrombocytopenic state at diagnosis than those with the AG genotype (P = 0.04). We concluded from our results that interleukin-17F rs763780 (7488A/G) polymorphism is strongly correlated with susceptibility and severity of ITP.

Association of interleukin (IL)-4 variable number of tandem repeats (VNTRs) and IL-4-590 promoter polymorphisms with susceptibility to pediatric autoimmune hepatitis type 1.

OBJECTIVE: Autoimmune hepatitis (AIH) is a chronic inflammatory liver disease mediated by an autoimmune reaction to hepatocytes, the present study aimed to assess the possible associations between interleukin-4 (IL-4) variable number of tandem repeats (VNTRs) and IL-4-590 promoter polymorphisms and susceptibility to autoimmune hepatitis type 1 in children. SUBJECTS AND METHODS: The study was performed on 101 children diagnosed with AIH and 104 apparently healthy, age and sex-matched control children, diagnosis of AIH was based on the simplified score for the diagnosis of AIH. Genotyping for the IL-4 VNTR and IL-4-590 were performed using PCR-RFLP. RESULTS: The distribution of genotype frequencies of IL-4 gene intron 3 VNTR polymorphism were not significantly different between AIH patients and controls for 3R/2R and 2R/2R genotypes, while the 2R allele distribution was significantly higher among AIH patients than the control group. The frequency of IL-4-590 single nucleotide polymorphism (SNP) CT and TT genotypes was statistically higher among AIH patients than controls. CONCLUSION: This study revealed the presence of an association between IL-4 -590 TT genotype and T alleles with increased AIH risk in pediatric patients, also assess its severity as they were detected with Child Plugh scores B and C.

Role of serum cystatin-C and beta-2 microglobulin as early markers of renal dysfunction in children with beta thalassemia major.

BACKGROUND: Although advancements have been made in the management of thalassemic patients, many unrecognized complications have emerged, such as renal abnormalities. AIM: To measure serum levels of cystatin-C and ß-2 microglobulin in children with beta-thalassemia major (ß-TM) and investigate their significance as early markers of glomerular and tubular dysfunctions. SUBJECTS AND METHODS: The study was performed on 70 children with (ß-TM) and 20 apparently healthy children matched for age and sex as a control group. For all the enrolled children, a comprehensive medical history was obtained and complete physical examination was performed, blood urea, serum creatinine, serum ferritin, estimated glomerular filtration rate (eGFR) by Schwartz formula and creatinine clearance, albumin/creatinine ratio in urine, serum cystatin-C levels and ß-2 microglobulin were measured. RESULTS: Thalassemic children had significantly higher cystatin-C and ß-2 microglobulin levels compared with control. In addition, serum cystatin-C and ß-2 microglobulin were positively correlated with urea, creatinine, serum ferritin, albumin/creatinine ratio, duration of chelation therapy and frequency of blood transfusion/year and negatively correlated with creatinine clearance, hemoglobin, and eGFR. Our data demonstrated that cystatin-C and ß-2 microglobulin had higher sensitivity and specificity (91.4%, 90.0%, and 85.7%, 100%, respectively) than serum creatinine and creatinine clearance (83.0%, 100% and 81.4%, 100%, respectively) for small changes in GFR. CONCLUSION: Cystatin-C and ß-2 microglobulin are specific and sensitive early biomarkers for monitoring glomerular and tubular dysfunction in children with ß-TM.

Predictive value of IL-35 and IL-17 in diagnosis of childhood asthma.

This study aimed to evaluate the correlation between serum levels of IL-17 and IL-35 and the presence and severity of childhood asthma. The study was performed on 60 diagnosed asthmatic children, who were further classified into four groups according to the Global Initiative for Asthma Guidelines for Asthma Severity and Control (GINA) 2016, plus 30 age- and sex-matched apparently healthy children. All participants were subjected to full medical history, clinical examination, pulmonary function tests and laboratory evaluation in the form of complete blood count (CBC), serum total IgE, IL-17 and IL-35 by ELISA. Our results revealed that eosinophils count, IgE and IL-17 were significantly higher in the asthmatic group than the control group (p < .001), while IL-35 levels were significantly lower in asthmatics than control (p < .001). A strong negative correlation was found between serum IL-17 and serum IL-35; a positive correlation was found between serum IL-17 and both of serum total IgE and eosinophils counts in atopic asthmatic patients, and serum IL-35 showed significant negative correlations with both. ROC analysis of the data showed that the cut-off value of IL-35 level was <189.5 pg/mL and for IL-17 level, it was >13.1 pg/mL; this value could predict childhood asthma with sensitivity of 81.7% and 83.3%, and specificity of 76.7% and 70%, respectively. A combination of both cytokines yielded an increase in sensitivity to 95%. In conclusion, in the current study, IL-17 is upregulated while IL-35 is downregulated in childhood asthma with a significant negative correlation between both. These results suggest that both may play an important role in the pathogenesis of childhood asthma.