Increased IRF4 expression in isolated B cells from common variable immunodeficiency (CVID) patients

Background: Common variable immunodeficiency (CVID) is a heterogeneous disorder characterized by low serum levels of immunoglobulins (Igs) and recurrent infection. In most CVID patients, a defect in the differentiation of B cells into plasma cells has been observed. Several factors play an important role in the proliferation and differentiation of B cells, including IRF4 and XBP1 transcription factors. Methods: In the present study we investigated the expression of IRF4 and XBP1 in the B-cells of CVID and healthy controls (HCs). For this purpose, we assessed the expression of IRF4 and XBP1 at both mRNA and protein levels by real time-PCR and flow cytometry, respectively. Results: We found that IRF4 expression was significantly increased in CVID patients compared with controls. Although the XBP1 protein level was lower in patients in comparison to controls, this difference was not significant. Conclusion: Taken together, increased IRF4 expression could be involved in defective functions of B cells in CVID patients

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Increased IRF4 expression in isolated B cells from common variable immunodeficiency (CVID) patients.

BACKGROUND: Common variable immunodeficiency (CVID) is a heterogeneous disorder characterized by low serum levels of immunoglobulins (Igs) and recurrent infection. In most CVID patients, a defect in the differentiation of B cells into plasma cells has been observed. Several factors play an important role in the proliferation and differentiation of B cells, including IRF4 and XBP1 transcription factors. METHODS: In the present study we investigated the expression of IRF4 and XBP1 in the B-cells of CVID and healthy controls (HCs). For this purpose, we assessed the expression of IRF4 and XBP1 at both mRNA and protein levels by real time-PCR and flow cytometry, respectively. RESULTS: We found that IRF4 expression was significantly increased in CVID patients compared with controls. Although the XBP1 protein level was lower in patients in comparison to controls, this difference was not significant. CONCLUSION: Taken together, increased IRF4 expression could be involved in defective functions of B cells in CVID patients.

Decreased serum levels of interleukin-35 among multiple sclerosis patients may be related to disease progression.

The regulatory role of interleukin (IL) -35 in the immunopathogenesis of multiple sclerosis (MS) is suggested in very few studies. We aimed to measure serum levels of IL-35 among clinically isolated syndrome (CIS) and relapsing-remitting MS (RRMS) patients and evaluate the associations between this cytokine and the disease clinical course. This cross-sectional study was conducted during 2017 in a referral university clinic. Forty patients and 40 healthy controls were included in the study. The level of IL-35 in the serum of all subjects was determined by ELISA. Serum level of IL-35 was reduced (p = 0.003) in RRMS in comparison with healthy controls. Moreover, the mean serum level of IL-35 among new cases (diagnosed within the 6 months prior to the study) decreased compared to healthy controls but it was not statistically significant (P=0.059). The mean serum level of IL-35 was significantly higher in new cases compared with other cases (p=0.048). Overall, we found decreased serum level of IL-35 among RRMS patients compared to the healthy controls. Our finding provides a view of the possible role of IL-35 in MS pathogenesis and the potential therapeutic targets.

The apoptotic effects of sirtuin1 inhibitor on the MCF-7 and MRC-5 cell lines.

Sirtuin1 (SIRT1) is an enzyme that deacetylates histones and several nonhistone proteins including p53 during stress and plays an important role in the survival of tumor cells. Hereby, this study describes the potency of salermide as a SIRT1 inhibitor to induce apoptosis in the MCF-7 and MRC-5 cell lines. MCF7 and MRC-5 cell lines were cultured in RPMI-1640 and treated with or without salermide at concentration of 80.56 µmol/L, based on the half-maximal inhibitory concentration (IC50) index at different times (24, 48 and72 h). The IC50 value was established for the salermide in MCF-7. The percentage of apoptotic cells was measured by flow cytometry. Real-time quantitative RT-PCR was performed to estimate the mRNA expression of sirtuin1 in MCF-7 and MRC-5 with salermide at different times. ELISA and Bradford protein techniques were used to detect endogenous levels of total and acetylated p53 protein generated in MCF-7 and MRC-5 cells. Our findings indicated that salermide can induce apoptosis in MCF-7 significantly more effective than MRC-5 cells. We showed that the expression of SIRT1 was dramatically down-regulated by increasing the time of salermide treatment in MCF-7 but not MRC-5 and that the acetylated and total p53 protein levels were increased more in MCF-7 than MRC-5. Salermide, by decreasing the expression of sirtuin1 gene, can induce acetylation of P53 protein and consequently induce significant cell death in MCF-7 that was well tolerated in MRC-5.

Association of angiotensin converting enzyme gene (I/D) polymorphism with hypertension and type 2 diabetes.

OBJECTIVES: This study was conducted to determine the association of insertion/deletion (I/D) polymorphism of the ACE gene in hypertensive and T2DM subjects in Egyptian population. BACKGROUND: The deletion (D) allele of the angiotensin-converting enzyme (ACE) gene has been studied in relation to hypertension and type 2 diabetes mellitus (T2DM) with contradictory results which might be due to ethnic and geographical variations. METHODS: A total of 85 subjects participated in this study; hypertension (Group 1); type 2 diabetes mellitus (Group 2) and controls (Group 3). Written informed consent was obtained. for each subject: age, sex, diabetes duration and the drugs used, blood pressure (systolic and diastolic), and lipid profile. Genotyping was performed by polymerase chain reaction (PCR). RESULTS: The frequency of DD genotype was significantly higher in hypertensive (60 %) and diabetic patients (68 %) compared to controls (33.3 %) (p=0.04, p=0.01 respectively). The DD genotype (vs DI and II genotype) in the hypertensive and diabetic groups is associated with increased risk of hypertension and/or diabetes. OR=3.00; 95%, Cl = 0.993-9.067; OR=4.250; 95%, Cl = 1.234-14.63 respectively). The D allele was more frequent in hypertensive (77.5 %) and diabetic patients (82 %) compared to controls (52.4 %) (p=0.004 and 0.002 respectively). The D allele (vs the I allele) is associated with increased risk of hypertension and diabetes OR=3.13, 95%Cl=1.405-6.978; OR= 4.14, 95% CI= 1.615-10.622 respectively). CONCLUSION: The DD genotype and the D allele are associated with hypertension and type 2 diabetes in Egyptian patients (Tab. 5, Fig. 1, Ref. 32).