Th1/Th2/Th17/Treg cytokine imbalance in systemic lupus erythematosus (SLE) patients: Correlation with disease activity.

AIM: Imbalance of T-helper-cell (TH) subsets (TH1/TH2/TH17) and regulatory T-cells (Tregs) is suggested to contribute to the pathogenesis of Systemic lupus erythematosus (SLE). Therefore, we evaluated their cytokine secretion profile in SLE patients and their possible association with disease activity. METHODS: Sixty SLE patients, 24 rheumatoid arthritis (RA) patients and 24 healthy volunteers were included in this study. Demographic, clinical, disease activity and serological data were prospectively assessed. Plasma cytokines levels of TH1 (IL-12, IFN-γ), TH2 (IL-4, IL-6, IL-10), TH17 (IL-17, IL-23) and Treg (IL-10 and TGF-ß) were measured by enzyme linked immunosorbent assays (ELISA). RESULTS: SLE patients were found to have significantly higher levels of IL-17 (p<0.001), IL-6 (p<0.01), IL-12 (p<0.001) and IL-10 (p<0.05) but comparable levels of IL-23 and IL-4 and slight reduction (but statistically insignificant) of TGF-ß levels compared to controls. IL-6, IL-10 and IL-17 were significantly increased (p<0.05) with disease activity. The RA group exhibited significantly higher levels of plasma IL-4 (p<0.01), IL-6 (p<0.05), IL-17 (p<0.001), IL-23 (p<0.01) and TGF-ß (p<0.5) and lower IFN-γ (p<0.001) and IL-10 (p<0.01) than those of healthy subjects. CONCLUSION: Our study showed a distinct profile of cytokine imbalance in SLE patients. Reduction in IFN-γ (TH1) and TGF-ß1 (Treg) with the elevation in IL-6 and IL-17 (TH17) could imply skewing of T-cells toward TH17 cells. Breaking TH17/Treg balance in peripheral blood may play an important role in the development of SLE and could be responsible for an increased pro-inflammatory response especially in the active form of the disease.

Cost-effectiveness model for hepatitis C screening and treatment: Implications for Egypt and other countries with high prevalence.

Hepatitis C virus (HCV) infection is a major cause of cirrhosis and liver cancer, and many developing countries report intermediate-to-high prevalence. However, the economic impact of screening and treatment for HCV in high prevalence countries has not been well studied. Thus, we examined the cost-effectiveness of screening and treatment for HCV infection for asymptomatic, average-risk adults using a Markov decision analytic model. In our model, we collected age-specific prevalence, disease progression rates for Egyptians and local cost estimates in Egypt, which has the highest prevalence of HCV infection (~15%) in the world. We estimated the incremental cost-effectiveness ratio and conducted sensitivity analyses to determine how cost-effective HCV screening and treatment might be in other developing countries with high and intermediate prevalence. In Egypt, implementing a screening programme using triple-therapy treatment (sofosbuvir with pegylated interferon and ribavirin) was dominant compared with no screening because it would have lower total costs and improve health outcomes. HCV screening and treatment would also be cost-effective in global settings with intermediate costs of drug treatment (~$8000) and a higher sustained viral response rate (70-80%).

Polymorphisms of interleukin 6 and interleukin 10 in Egyptian people with Behcet's disease.

Cytokines play critical roles in the pathogenesis of Behçet's disease (BD). They mediated many of the effectors and regulatory functions of immune and inflammatory responses. Many studies have linked Interleukin-6 (IL-6) and Interleukin-10 (IL-10) pathologically to BD. Thus, this study aimed to investigate the associations between IL-6 and IL-10 promoter single-nucleotide polymorphisms (SNPs) and the susceptibility to BD and their implication on plasma levels. We genotyped IL-6 -174 G/C (rs1800795) using Mutagenically Separated Polymerase Chain Reaction PCR (MS-PCR) and IL-10 -1082 G/A (rs1800896) and -819 C/T (rs1800871) using Sequence Specific Primer PCR (SSP-PCR) in 87 Egyptian patients and 97 controls. The plasma levels of IL-6 and IL-10 were measured using Enzyme-linked Immunosorbent Assay (ELISA). Significant increase in the frequency of -1082 GG genotype (P<0.05, OR=2.25, 95%CI=1.03-4.91) and significant decrease in the frequency of -1082 GA genotype (P<0.05, OR=0.53, 95%CI=0.29-0.96) was demonstrated in BD patients compare to controls. Patients with genital ulcer had significantly lower frequency of -1082 GG (P<0.05, OR 0.2, 95% CI=0.04-0.99) and G allele (P<0.05, OR=0.28, 95%CI=0.08-0.93), while patients with ocular manifestations had significantly higher frequency of -1082 G allele (P<0.01, OR=2.28, 95%CI=1.19-4.36). BD patients had significantly higher level of IL-6 (P<0.001) and significantly lower level of IL-10 (P<0.001) compared to controls. The changes in the level of cytokines were independent of any genotype of IL-6 or any genotype/haplotype of IL-10. Patients with active disease state had significantly higher level of IL-6 compared to patients in remission (P<0.05). In conclusion, our preliminary study indicates that the polymorphism at IL-10 -1082 G/A may play a role in BD susceptibility. The significant increase in IL-6 level and the significant decrease in IL-10 level in BD patients were independent of any particular genotype in IL-6 or any particular genotype/haplotype in IL-10.

Plasma protein advanced glycation end products, carboxymethyl cysteine, and carboxyethyl cysteine, are elevated and related to nephropathy in patients with diabetes.

In Diabetes Mellitus (DM), glucose and the aldehydes glyoxal and methylglyoxal modify free amino groups of lysine and arginine of proteins forming advanced glycation end products (AGEs). Elevated levels of these AGEs are implicated in diabetic complications including nephropathy. Our objective was to measure carboxymethyl cysteine (CMC) and carboxyethyl cysteine (CEC), AGEs formed by modification of free cysteine sulfhydryl groups of proteins by these aldehydes, in plasma proteins of patients with diabetes, and investigate their association with the albumin creatinine ratio (ACR, urine albumin (mg)/creatinine (mmol)), an indicator of nephropathy. Blood was collected from forty-two patients with type 1 and 2 diabetes (18-36 years) and eighteen individuals without diabetes (17-35 years). A liquid chromatography-mass spectrophotometric method was developed to measure plasma protein CMC and CEC levels. Values for ACR and hemoglobin A1C (HbA1C) were obtained. Mean plasma CMC (microg/l) and CEC (microg/l) were significantly higher in DM (55.73 +/- 29.43, 521.47 +/- 239.13, respectively) compared to controls (24.25 +/- 10.26, 262.85 +/- 132.02, respectively). In patients with diabetes CMC and CEC were positively correlated with ACR, as was HbA1C. Further, CMC or CEC in combination with HbA1C were better predictors of nephropathy than any one of these variables alone. These results suggest that glucose, glyoxal, and methylglyoxal may all be involved in the etiology of diabetic nephropathy.