Toll-like receptor 7 gene single nucleotide polymorphisms and the risk for systemic lupus erythematosus: a case-control study.

BACKGROUND: Toll-like receptors (TLRs) are a family of pattern-recognition receptors which play a role in eliciting innate/adaptive immune responses and developing chronic inflammation. So, the aim of this study was to analyze the effect of TLR7 gene single nucleotide polymorphisms (SNPs) rs3853839 and rs179019 on systemic lupus erythematosus (SLE) susceptibility and to assess their relations with various clinical and laboratory data of the patients. METHODS: This is a case-control study including 50 SLE female patients and 50 healthy controls. TLR7 rs3853839 and rs179019 genotyping was performed using real-time polymerase chain reaction (PCR) TaqMan-based allelic discrimination assay. RESULTS: Regarding rs3853839, there was a statistically significant difference in the distribution of the genotypes between SLE patients and the control group in our study (P = 0.009). A significant association was detected between TLR7 genotypes (rs385389) and lupus nephritis (p = 0.021). Regarding rs179019, there was no statistically significant difference in the distribution of the genotypes between SLE patients and the control group in our study (P = 0.271) CONCLUSION: This study revealed the plausible role of TLR7 rs3853839 SNP in SLE in Egyptian women.

Schistosome infection aggravates HCV-related liver disease and induces changes in the regulatory T-cell phenotype.

Schistosome infections are renowned for their ability to induce regulatory networks such as regulatory T cells (Treg) that control immune responses against homologous and heterologous antigens such as allergies. However, in the case of co-infections with hepatitis C virus (HCV), schistosomes accentuate disease progression and we hypothesized that expanding schistosome-induced Treg populations change their phenotype and could thereby suppress beneficial anti-HCV responses. We therefore analysed effector T cells and n/iTreg subsets applying the markers Granzyme B (GrzB) and Helios in Egyptian cohorts of HCV mono-infected (HCV), schistosome-co-infected (Sm/HCV) and infection-free individuals. Interestingly, viral load and liver transaminases were significantly elevated in Sm/HCV individuals when compared to HCV patients. Moreover, overall Treg frequencies and Helios(pos) Treg were not elevated in Sm/HCV individuals, but frequencies of GrzB(+) Treg were significantly increased. Simultaneously, GrzB(+) CD8(+) T cells were not suppressed in co-infected individuals. This study demonstrates that in Sm/HCV co-infected cohorts, liver disease is aggravated with enhanced virus replication and Treg do not expand but rather change their phenotype with GrzB possibly being a more reliable marker than Helios for iTreg. Therefore, curing concurrent schistosome disease could be an important prerequisite for successful HCV treatment as co-infected individuals respond poorly to interferon therapy.

Stimulation of long-chain fatty acid uptake by dipyridamole in isolated myocytes.

This study was designed to investigate the effects of the cardiovascular drug dipyridamole on fatty acid metabolism in isolated cardiac myocytes. Effects of dipyridamole on the oxidation of long-chain (palmitate) fatty acid, medium-chain (octanoate) fatty acid, and the carbohydrate intermediate (pyruvate) were determined by using isolated cardiac myocytes from both normal and diabetic rats. Dipyridamole increased palmitate oxidation in a concentration-dependent manner in both normal and diabetic myocytes. Maximal stimulation of palmitate oxidation (175% of control) was observed with 100 microM dipyridamole. In contrast, oxidation of octanoate and pyruvate was not affected. The stimulation of palmitate oxidation by dipyridamole persisted despite its removal from the incubation medium. In contrast to the effect in myocytes, palmitate oxidation was not affected by dipyridamole in isolated rat heart mitochondria. Palmitate uptake was increased by 2.5- and 1.6-fold when palmitate concentration was adjusted to 0.05 and 0.2 mM, respectively. Dipyridamole did not affect lipolysis in isolated myocytes. When dipyridamole (100 microM) and L-carnitine (5 mM) were added together to the incubation medium, palmitate oxidation was further increased to 223% of the control. The nucleoside transport inhibitor nitrobenzylthioinosine (NBMPR) failed to increase palmitate oxidation in isolated myocytes. Although palmitate oxidation in diabetic cells is much higher than that in normal myocytes, dipyridamole increased palmitate oxidation by 243% in diabetic myocytes over its baseline oxidation rate in normal cells. These results suggest that increased palmitate oxidation in isolated cardiac myocytes after dipyridamole administration occurs independent of effects on either the phosphodiesterase enzyme or nucleoside transport protein, but it may result from increased palmitate transport across the plasma membrane.