Angiotensin converting enzyme [ACE] l/D gene polymorphism in children with idiopathic nephrotic syndrome

Various genetic markers have been studied to predict susceptibility and course of nephrotic syndrome. The Angiotensin-converting enzyme [ACE] gene carries insertion [I] and deletion [D]polymorphism within its intron 16. The presence of D-allele in the ACE gene has been reported as a probable genetic risk factor for idiopathic nephrotic syndrome [INS] and may be also related to poor responsiveness to steroids which is the single most important clinical parameter in determining the course of the disease. The aim is to determine the distribution of the ACE gene insertion/deletion [l/D] polymorphism, and its effect on clinical, laboratory, histological findings and therapeutic response in childhood INS. Fifty one nephrotic syndrome patients [35 males and 16 females] were enrolled in the study. All patients received oral steroids as in initial therapy for their nephrotic syndrome. The pattern of response to steroid therapy was determined and patients divided into 2 groups: steroid sensitive [SS] and non-steroid sensitive [non-SS]. The non-SS group was further divided into steroid dependent [SD] and steroid resistant [SR] patients. Clinical, laboratory and histological features were determined. Fifty unrelated healthy adults were recruited as controls. The genotypes for ACE l/D polymorphism were analyzed by using a PCR based method. Twenty patients were SS and 31 were non-SS, of the non-SS group, 18 were SD and 13 were SR. The presence of hypertension at presentation was significantly related to steroid unresponsiveness. Among the SS group the frequencies of the Ii, ID, and DD genotypes of the ACE gene were 20%[n=4], 65%[n=13] and 15%[n=3], respectively, while the frequencies among the Non-SS group were 19.4%[n=6], 74.2%[n=23] and 6.5%[n=2], respectively. The differences between the two groups were statistically insignificant [Chi square=0.59]. The corresponding incidence for control was 12%, 68% and 10% respectively. The differences between controls versus the entire patient group, the SS group and the non-SS group were not statistically significant [p value>0.05 in all]. The frequency of D+genotype was 80%[n=16] in the SS group compared to 80.6%[n=25] in the Non-SS group, the difference between the two groups was statistically insignificant [Fisher's exact=1]. The pattern of the ACE gene polymorphism showed insignificant correlation with age of onset of the disease, hypertension at presentation, stability of renal functions and renal biopsy results. The current study on Egyptian children with INS reveals no association between ACE gene l/D polymorphism and clinical, histological findings, steroid responsiveness, or progression of the disease These results are at variance with reports from other parts of the world suggesting that the impact of ACE gene polymorphism on pediatric INS is likely to be influenced by the ethnic origin. Results of this study revealed an association between hypertension at presentation and non-responsiveness to steroid. Patients with steroid non responsiveness were more liable to develop impaired renal function

role of Thrombomodulin, IL-12, transforming growth factor-beta2 in early onset preeclamsia: a potential biomarker for disease severity

Early onset Preeclampsia is a pregnancy specific heterogeneous syndrome with genetic predisposition ranging from hypertension, proteinuria and edema to severe preeclampsia with complications. A defective implantation and placentation, circulating factors including proinflammatory molecules, cytokines and adhesion molecules have been implicated in the pathogenesis of preeclampsia. Was to assess the clinical value of assaying maternal serum concentration of thrombomodulin [TM] interleukin-12 [IL-12] and transforming growth factor beta-2 [TGF-beta 2], in normotensive, mild and severe preeclamptic pregnant women, and to evaluate the correlation between these factors and the blood pressure, uric acid and creatinine. The second objective was to look for differences between mild and severe early onset preeclampsia, compared with a healthy pregnant and non pregnant cross sectional investigated groups. Serum TM, IL-12 and TGF-beta 2 were measured using enzyme linked immunoassay [ELISA] and enzyme immunoassay respectively in 45 women with preeclampsia divided into 24 mild and 21 severe preeclamptic patients and compared with 21 pregnant normotensive and 20 non pregnant controls. Serum uric acid and creatinine were measured as well. Severe preeclamptic women had significantly increased levels of TM [p<0.01], IL-12 [p<0.01] and TGF-beta 2 p<0.01] compared with women with normal pregnancy and non pregnant women. Serum creatinine and uric acid co1Icentrations were significantly higher in severe preeclamptic patients [1.35 +/- 0.17mg/dL, 7.43 +/- 0.74mg/dL, respectively, mean +/- SD] and did not change significantly in mild preeclamptic women compared with those of healthy normotensive pregnant women. Significant positive correlations existed between serum TGF-beta 2 concentrations and mean arterial blood pressure, TM. serum creatinine and uric acid concentrations in severe pre peclamptic patients. Conclusion: Increase concentration of thrombomodulin, II-12 and TGF-beta 2, in severe preeclamptic patient might explain the shallow placentation, endothelial cell dysfunction and renal involvement described in severe preeclampsia. Measurement of maternal plasma of TM, IL-l2, TGF-beta 2 levels in preeclampsia can be useful biomarker for the assessment of the severity of the disease

Molecular identification of coproantigens of Cryptosporidium parvum compared to conventional staining techniques

To compare the immunologic techniques with the conventional staining methods [mainly modified Ziehl-Neelsen, MZN], 93 children [65 immunocompromised and 28 immunocompetent] potentially at risk of Cryptosporidium parvum were studied. Using MZN, a prevalence of 10.7% in diarrheic children was found. ELISA coproantigen and detection of 23 kDa band of immunoblotting by serum IgG were sensitive and specific. They gave 85.7% sensitivity, 100% specificity, 100% diagnostic accuracy, 100% positive predictive value and 98.9% negative predictive value. ELISA detection of serum IgG gave 85.7% sensitivity, 97.7% specificity, 96.8% diagnostic accuracy, 75% positive predictive value and 98.9% negative predictive value. So, it was concluded that 23 kDa band determined by ELISA is a valuable sensitive and specific mean of diagnosing cryptosporidiosis, as this antigen is a consistent target of the humoral immune response