Toll-like receptor 3 gene expression in Egyptian patients with glomerulonephritis and hepatitis C virus infection.

BACKGROUND: Hepatitis C virus (HCV) infection is associated with both chronic liver disorders and several extrahepatic manifestations including renal disease. Toll-like receptor 3 (TLR3), a component of the innate immune system, is a pathogen recognition receptor that recognizes viral double-stranded RNA. OBJECTIVE: This work investigated TLR3 expression in peripheral blood mononuclear cells from HCV-positive patients with glomerulonephritis. METHODS: One hundred and thirty patients with glomerulonephritis were initially enrolled in the study. After exclusion of 52 patients with secondary glomerulonephritis, 78 patients were screened for HCV infection. TLR3 expression in peripheral blood mononuclear cells was studied in 46 patients with HCV-positive glomerulonephritis and 32 patients with HCV-negative glomerulonephritis using a real-time PCR comparative quantitation approach and results were compared to a control group of 20 healthy subjects. RESULTS: TLR3 expression was significantly higher in patients with HCV-positive glomerulonephritis than in HCV negative patients and controls (p < 0.0001). TLR3 expression correlated positively with HCV viral load, interleukin-1ß, serum creatinine and inversely with creatinine clearance in patients with HCV-positive glomerulonephritis. CONCLUSION: This work shows that TLR3 expression is upregulated in HCV-positive patients with glomerulonephritis. Overexpression is associated with reduced renal function and increased interleukin 1ß level.

MEFV gene mutations in Egyptian patients with familial Mediterranean fever.

BACKGROUND: Familial Mediterranean fever (FMF) is an autosomal recessive disorder characterized by recurrent attacks of fever and serositis. The disease affects mainly Mediterranean populations and is caused by mutations in the MEFV gene. AIM: This work was carried out to identify and determine the frequencies of MEFV gene mutations in Egyptian patients in whom FMF was diagnosed. METHODS: We investigated 316 patients with a clinical diagnosis of FMF for 12 MEFV mutations including the 5 most common known mutations M694V, V726A, M694I, M680I, and E148Q by allele-specific hybridization. RESULTS: Mutations were detected in 182 (57.6%) patients: 20 were homozygous, 80 were compound heterozygous, and 82 had only one identifiable mutant allele. In patients with clinically definite FMF (n = 112), no mutations were detected in 28 patients; whereas in patients with clinically unlikely FMF (n = 48), genetic analysis established the diagnosis in 6 patients. Overall, 10 mutations were detected in our patients. The most common were M694I (34%), E148Q (22.7%), V726A (15.6%), M680I (12.1%), and M694V (7.8%). M694V was observed in severe disease and in patients with amyloidosis. CONCLUSION: We were able to identify a wide spectrum of MEFV mutations in Egyptian patients in whom FMF was diagnosed. Frequencies of individual mutations showed some differences from those in other Mediterranean populations.