Association of ELMO1 gene polymorphism and diabetic nephropathy among Egyptian patients with type 2 diabetes mellitus.

BACKGROUND AND OBJECTIVE: Diabetic nephropathy (DN) is the most common cause of end stage renal failure or even death among patients with type 2 diabetes mellitus. Genetic predisposition is widely studied among these patients to identify manageable aspects of the disease pathogenesis. This study was carried out to test the association of engulfment and cell motility 1 (ELMO1) gene polymorphism with DN among Egyptians. ELMO1 is required for phagocytosis of apoptotic cells and cell motility. METHODS: This case-control study was conducted on type 2 diabetic patients who attended Suez Canal University Hospital, Egypt, between November 2016 and October 2017. Peripheral blood was collected from 200 diabetic patients (without nephropathy), 200 patients with DN, and 100 healthy controls for DNA extraction. The single nucleotide polymorphism of ELMO1 (rs741301) was genotyped using real-time polymerase chain reaction and the allele discrimination technique. RESULTS: GG genotype was significantly associated with DN (odds ratio [OR] = 2.7; 95% confidence interval [CI]: 1.4-5.3) (P = .016). The OR for the high-risk allele (G) was 1.9 with 95% CI from 1.5 to 2.9 (P < .001). CONCLUSION: ELMO1 gene (rs741301) polymorphism is a candidate variant in the predisposition to DN.

α-Adducin gene promoter DNA methylation and the risk of essential hypertension.

This study was conducted to test the association between promoter DNA methylation of α-Adducin (ADD1) gene and the risk of essential hypertension (EH). A total of 150 EH patients and 100 aged- and gender-matched controls were investigated. DNA methylation levels of five cytosine-phosphate-guanine (CpG) dinucleotides on ADD1 promoter were measured employing bisulfite pyrosequencing technology. Our results showed that females have a higher ADD1 DNA methylation than males and a significantly lower CpG1 methylation level is associated with increased risk of EH among them. As for males, a significant association between lower CpG2-5 methylation levels and increased risk of EH was shown. In addition, CpG2-5 methylation was found to be a highly significant predictor for EH among males. In females, CpG1 methylation was considered a predictor of hypertension. No significant correlations were found with biochemical measures, apart from the concentration of aspartate aminotransferase which was inversely correlated with ADD1 CpG2-5 methylation levels among female controls (r = -0.703). These findings highlight that ADD1 methylation may have a contributing role in the pathogenesis of EH with varying implications for both genders.

MicroRNA-29a and microRNA-122 expressions and other inflammatory markers among obese children with diabetes.

OBJECTIVES: This study was conducted to study the expression of both microRNA-29a and microRNA-122, and serum levels of sestrin-2, interleukin-6 (IL-6), and other inflammatory markers among obese children with/and without diabetes mellitus. METHODS: One hundred obese children with diabetes in addition to 100 age- and sex-matched obese children without diabetes, and 100 age- and sex-matched apparently healthy children were included in the study. Expressions of both microRNA-29a and microRNA-122, and serum levels of sestrin-2, IL-6, tumor necrosis factor-α (TNF-α), and high sensitive-CRP (hsCRP) were measured for all included study populations. RESULTS: Study results showed that the expressions of both microRNA-29a and microRNA-122, serum levels of IL-6, TNF-α, and hsCRP were significantly higher among obese children with diabetes in comparison to both obese children without diabetes and healthy children. In contrast, serum sestrin level was significantly low among obese children with diabetes in comparison to the other study populations. Expressions of both microRNA-29a and microRNA-122 were correlated with waist circumference, BMI, total cholesterol, triglycerides, LDL-cholesterol, HbA1c, c-peptide, glucose, insulin, homeostatic model assessment-insulin resistance (HOMA-IR), IL-6, hsCRP, and TNF-α among obese children with diabetes. However, serum sestrin-2 level was correlated inversely with these parameters. Higher expressions of both microRNA-29a and microRNA-122 among obese children either with or without diabetes mellitus (DM) can suggest their roles in the development of obesity among children. CONCLUSIONS: The study results can hypothesize that down-regulation of these micro-RNAs may solve this health problem with its sequelae, a hypothesis that needs more studies.

Response to rituximab-based therapy and risk factor analysis in Epstein Barr Virus-related lymphoproliferative disorder after hematopoietic stem cell transplant in children and adults: a study from the Infectious Diseases Working Party of the European Group for Blood and Marrow Transplantation.

BACKGROUND: The objective of this analysis was to investigate prognostic factors that influence the outcome of Epstein-Barr virus (EBV)-related posttransplant lymphoproliferative disorder (PTLD) after a rituximab-based treatment in the allogeneic hematopoietic stem cell transplant (HSCT) setting. METHODS: A total of 4466 allogeneic HSCTs performed between 1999 and 2011 in 19 European Group for Blood and Marrow Transplantation centers were retrospectively analyzed for PTLD, either biopsy-proven or probable disease. RESULTS: One hundred forty-four cases of PTLD were identified, indicating an overall EBV-related PTLD frequency of 3.22%, ranging from 1.16% for matched-family donor, 2.86% for mismatched family donor, 3.97% in matched unrelated donors, and 11.24% in mismatched unrelated donor recipients. In total, 69.4% patients survived PTLD. Multivariable analysis showed that a poor response of PTLD to rituximab was associated with an age ≥30 years, involvement of extralymphoid tissue, acute GVHD, and a lack of reduction of immunosuppression upon PTLD diagnosis. In the prognostic model, the PTLD mortality increased with the increasing number of factors: 0-1, 2, or 3 factors being associated with mortality of 7%, 37%, and 72%, respectively (P < .0001). Immunosuppression tapering was associated with a lower PTLD mortality (16% vs 39%), and a decrease of EBV DNAemia in peripheral blood during therapy was predictive of better survival. CONCLUSIONS: More than two-thirds of patients with EBV-related PTLD survived after rituximab-based treatment. Reduction of immunosuppression was associated with improved outcome, whereas older age, extranodal disease, and acute graft-vs-host disease predicted poor outcome.

Association of IL-16 rs11556218 T/G polymorphism with the risk of developing type 2 diabetes mellitus.

INTRODUCTION: Diabetes mellitus is a chronic disorder that has serious complications. Type 2 diabetes mellitus is more widespread worldwide and in Egypt. Interleukin-16 is a pro-inflammatory factor that can lead to many inflammatory diseases by stimulating the secretions of cytokines. Inflammation and obesity are concomitant factors that may lead to insulin resistance and type 2 diabetes mellitus. In this study, we tried to focus on the relation between Interleukin-16 rs11556218 polymorphism and the risk of development of type 2 diabetes mellitus. PATIENTS AND METHODS: 128 type 2 diabetic patients and 128 healthy individuals as control were included in this case-control study. Interleukin-16 gene polymorphism (SNP rs11556218 T/G) was genotyped using a real-time polymerase chain reaction. RESULTS: Interleukin-16 rs11556218 T/G gene polymorphism has a statistically significant association with type 2 diabetes mellitus in the co-dominant, dominant and, over dominant genetic models. The genotype TG was presented in approximately 30 % of diabetic patients vs. control (p = 0.04) and patients with TG genotype have a 1.8 times higher risk for developing type 2 diabetes mellitus (OR1.87; 95 % CI = 1.04 to 3.39) and 9.5 times higher after risk-adjusted diabetes (OR9.58; 95 % CI = 1.50 to 61.25) (p = 0.031). We found an association between Interleukin-16 gene polymorphism with both body mass index and high density lipoprotein. CONCLUSION: This study is the first one in the Middle East and Africa which found a correlation between Interleukin-16 gene polymorphism rs11556218 and type 2 diabetes mellitus. Egyptians with TG genotypes have a higher risk to develop type 2 diabetes mellitus.

PPARα receptor expression in patients with metabolic syndrome.

BACKGROUND: Metabolic syndrome (MS) is considered one of the major worldwide epidemics. It accounts for billions of cardiovascular disease events and deaths. Till now, major basics of MS are not fully clarified. Peroxisome Proliferator-Activated Receptor-α (PPARα) displays a ligand-activated transcription factor. It is involved in the regulation of many metabolic processes including inflammation, lipid, and glucose metabolism. Therefore, this study investigated the leucocytic expression of PPARα in a metabolic patient in comparison to healthy controls. METHODS: 100 subjects with MS were recruited, in addition to 100 subjects without any obvious metabolic disorders as healthy controls. Expression of PPARα and CD 36 were analyzed on different leucocytic populations using optimized flow-cytometric analysis. Correlations of the expression of both indexes with different clinical and laboratory parameters were analyzed. RESULTS: The eosinophilic expression of PPARα was found to be lower in subjects with MS in comparison to the healthy controls (p value 0.001). Also, PPARα expression, on most of the leucocytic populations, was inversely correlated with waist circumferences among the study populations. CONCLUSION: Circulated eosinophilic expression of PPARα protein is reduced in MS subjects. This conclusion may explain the endothelial dysfunction and obesity associated with MS, as well as it may help in the management of this worldwide health problem.

25-hydroxyvitamin D Deficiency and Predictive Factors in Patients with Diabetic Nephropathy in Type 2 Diabetes Mellitus.

Diabetes mellitus is a metabolic disease that is characterized by chronic hyperglycemia. Type 2 diabetes is a global health problem and leading to many dangerous complications. Diabetic nephropathy is a significant microvascular complication resulting from diabetes mellitus that is affecting up to 50% of patients with end stage renal disease. Vitamin D deficiency may occur due to many different factors and is associated with many serious diseases as diabetic nephropathy. To investigate the 25-hydroxyvitamin D deficiency and predictive factors in patients with diabetic nephropathy in type 2 diabetes mellitus. One hundred type 2diabetic patients were divided into two groups according to Alb/creat ratio to diabetic patients with and without nephropathy and 50 non-diabetic controls. We measured the serum 25-hydroxyvitamin D levels in all the study populations. The mean serum level of 25 (OH) D was significantly decreased in patients with diabetic nephropathy (13.41±4.99 ng/ml, P=0.002). There was a significant correlation with vitamin D deficiency and the patients residency and also a significant positive correlation with eGFR (r = 0.317, P = 0.025) and a significant negative correlation with Alb/creat Ratio(r = -0.323, P = 0.022). The significant best-fitting predictors of vitamin D deficiency were living in rural area (OR=4.030, P < 0.021) and eGFR < 60 (OR=5.412, P < 0.034). In conclusion, vitamin D deficiency is prevalent in patients with diabetic nephropathy living in rural areas. Low eGFR < 60, Alb/creat ratio more than 30 mg/24h and HbA1c > 9 could be considered as predictive factors of vitamin D deficiency in these patients.

CD5+ B lymphocytes in systemic lupus erythematosus patients: relation to disease activity.

B cells are essential players in the pathogenic mechanisms of systemic lupus erythematosus (SLE). Although CD5+ B cells have been considered to play a paradoxical role in preventing, rather than inducing autoimmunity, there is no consensus agreement about the proportions of CD5+ B cells population in SLE patients. So, the aim of the present study was to assess blood concentration of CD5+ B cells in patients with SLE and to evaluate their relationship with disease activity and organ damage. We recruited 100 SLE patients and 100 healthy control subjects. Based on SLE disease activity index (SLEDAI), patients were divided into two groups: active SLE (n = 50) and inactive SLE (n = 50). SLE was active when SLEDAI was ≥ 4. The expression of CD5+ B cells was evaluated using flow cytometry to measure the proportions and absolute numbers of the cells. The proportions of CD5+ B cells of total lymphocytes were significantly lower in SLE patients versus controls (4.1 ± 3.9 vs 10.8 ± 5.2%, P = <0.001). CD5+ B cells were significantly decreased in active SLE patients (3.1 ± 2.7%) in comparison to inactive patients (5.2 ± 3.7%) (P = 0.013). CD5+ B cells correlated positively with C3 (r = 0.328, P = 0.020) and C4 (r = 0.355, P = 0.011). CD5+ B cells were significantly decreased in SLE patients compared to healthy controls and they were significantly decreased in active SLE patients in comparison to inactive ones.

Impact of schistosomiasis on increase incidence of occult hepatitis B in chronic hepatitis C patients in Egypt.

Co-infection of schistosomiasis, HBV and HCV is common in countries where schistosomiasis is endemic. Occult hepatitis B occurs in patients at high risk for HBV infection (e.g., patients on hemodialysis, patients receiving blood transfusions). Schistosomal infection is a risk factor of HBV infection that can increase the incidence of occult hepatitis B. We aimed to determine the prevalence of occult hepatitis B in chronic hepatitis C patients with and without schistosomiasis and to assess the effect of schistosomal infection on the increased risk of exposure to HBV infection and to occult hepatitis B. Two hundred chronic hepatitis C patients who were negative for HBsAg participated. All patients were tested for the following: Anti-schistosome antibodies, Anti-HBc, serum HBV DNA, CBC and liver function. The prevalence of occult hepatitis B in CHC patients with/without schistosomiasis were 12.8% and 8.5% (P=0.042), respectively. Next, 63.8% of CHC patients with schistosomiasis were exposed to HBV infection (Anti-HBc +ve) during their lifetime. In conclusion, the prevalence of occult hepatitis B is higher in CHC patients with schistosomiasis compared to those without schistosomiasis. Periodic laboratory investigations of Schistosoma mansoni, HBV and HCV are recommended for the early detection of the infection and, especially in endemic areas, to avoid infection complications.

Angiopoietin-2 as A Biomarker For Echocardiographic Abnormalities and Carotid Atherosclerosis In Rheumatoid Arthritis Patients.

Atherosclerosis and cardiovascular diseases (CVD) are increasingly recognised complications of rheumatoid arthritis (RA). Angiopoietin 2 (Ang-2) levels have been associated with clinically overt CVD in general population; we assessed serum Ang-2 levels and its correlation with Echocardiographic abnormalities and carotid intima-media thickness in RA patients. 44 RA patients without clinically overt CVD and 44 healthy controls were assessed by questionnaire and clinical examination. Disease activity score (DAS-28) was calculated. Laboratory investigations included measurement of serum Ang-2, Rheumatoid factor (RF), anti-cyclic citrullinated peptide (Anti-CCP), and C reactive protein (CRP). Doppler Echocardiography and Carotid ultrasonography were done to all patients and controls. Mean age of RA patients was 44.4±9.6 and about (86.4%) 38 were females. Mean levels of Ang-2 was higher in RA patients (17.591±13.9 ng/ml) as compared to controls (7.909 ±4.10 ng/ml) P<0.001 and was significantly elevated in RA patients with left ventricular (LV) diastolic dysfunction (23.53±7.75 ng/ml) than those without dysfunction (14.81±15.33ng/ml), P<0.05 and was significantly elevated in RA patients with carotid intima-media thickness (cITM) >0.6mm (21.12±14.79 ng/ml), P<0.005. Serum Ang-2 correlated positively with disease duration, DAS-28, LV posterior wall thickness, E wave velocity and cIMT. In conclusion, serum Ang-2 level is associated with LV diastolic dysfunction and increased carotid intima-media thickness in RA patients and may be useful biomarker for subclinical CVD and atherosclerosis in RA patients.

High incidence of chronic graft-versus-host disease after myeloablative allogeneic stem cell transplantation for chronic lymphocytic leukemia in Sweden: graft-versus-leukemia effect protects against relapse.

Allogeneic hematopoietic stem cell transplantation (allo-SCT) is a potentially curative treatment option for eligible patients with chronic lymphocytic leukemia (CLL). However, it is known that cure of CLL is only possible if a graft-versus-leukemia effect is present. Between 1994 and 2007, 48 adults underwent allo-SCT for poor-risk CLL in Sweden. Of these, ten (21%) patients aged 24-53 years (median: 46 years) received myeloablative conditioning (MAC), based on TBI and cyclophosphamide. All MAC patients had refractory, poorly controlled CLL before allo-SCT (partial remission in 9/10 patients and progressive disease in one). The cumulative incidence of acute graft-versus-host disease (GVHD) grades II-IV was 30%. Nine patients developed chronic GVHD; extensive in four. Rates of nonrelapse mortality at 1, 3 and 10 years were 0, 10 and 20%, respectively. Two patients relapsed 36 and 53 months after transplantation. Six patients were still alive after a median follow-up time of 11.5 years (range 5.9-13.7). The probabilities of relapse-free and overall survival from 1, 3 and 5 years after transplantation were 100, 90 and 70%, and 100, 90 and 80%, respectively. Nevertheless, our analysis of long-term outcome after MAC allo-SCT for CLL suggests that younger patients with poorly controlled CLL may benefit from MAC allo-SCT.

Allogeneic hematopoietic stem cell transplant with reduced-intensity conditioning for chronic lymphocytic leukemia in Sweden: does donor T-cell engraftment 3 months after transplant predict survival?

Thirty-eight adult patients with chronic lymphocytic leukemia (CLL) underwent reduced-intensity conditioning (RIC) allogeneic stem cell transplant (allo-SCT) in Sweden between 1999 and 2007. The cumulative incidences of acute graft-versus-host disease (GVHD) grades II-IV and chronic GVHD were 29% and 47%, respectively. Rates of non-relapse mortality, progression-free survival (PFS) and overall survival (OS) were 18%, 47% and 74% at 1 year, and 21%, 25% and 45% at 5 years, respectively. T-cell chimerism after transplant was measured in 31 out of 34 patients (91%) surviving beyond day +100. Seventeen patients achieved >90% donor T-cell engraftment at 3 months after allo-SCT and, compared with the 12 patients with ≤90% donor T-cell engraftment, they showed favorable PFS at 1 year (82% vs. 33%, p =0.002) and better long-term PFS and OS (p =0.002 and 0.046, respectively). Donor T-cell engraftment of >90% at 3 months after RIC allo-SCT for CLL seems to predict favorable short-term and long-term outcome.

Decreased IL-7 signaling in T cells from patients with PTLD after allogeneic HSCT.

Interleukin (IL)-7, a nonredundant cytokine for B and T cells, plays a central role in cell survival and immune memory formation. Peripheral blood mononuclear cells (PBMCs) from 7 patients after hematopoietic stem cell transplantation (HSCT) diagnosed with posttransplantation lymphoproliferative disease (PTLD) and from 10 Epstein-Barr virus (EBV) polymerase chain reaction-positive HSCT patients (controls) were evaluated for IL-7- and IL-2 induced Stat5 phosphorylation in CD4+ and CD8+ T cells. PBMCs from PTLD+ and control patients exhibited detectable EBV specific CD8+ T cells defined by tetramer analysis. CD4+ and CD8+ T cells from patients with PTLD showed statistically significant reduction in responsiveness to IL-7 compared with PBMCs obtained from controls defined by Stat5 phosphorylation. CD20+ B cells from patients with PTLD and from some EBV+ polymerase chain reaction control individuals exhibited IL-7R expression. Dysregulated immune surveillance, reflected by deficient Stat5 phosphorylation, may facilitate PTLD development despite the presence of EBV-reactive CD8+ T cells. Reduced IL-7 responsiveness will aid to monitor patients after HSCT for increased risk to develop EBV-associated PTLD.