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.

Circulating anti-HLA antibodies in patients with chronic hepatitis C: relation to disease activity.

The human leukocyte antigens (HLA) may influence host immune to infection. In the mean time chronic hepatitis C (CHC) results in the appearance of a variety of autoantibodies. We investigated the frequency of circulating anti-HLA antibodies and none organ specific autoantibodies in patients with chronic hepatitis C at different stages of disease activity. Sixty-seven untreated male patients with CHC (anti-HCV antibody and HCV RNA positive), in whom 38 had elevated serum alanine aminotransferase (ALT) levels and 29 persistently normal serum ALT values, and 23 age-matched normal male subjects were studied. None of them had a history of blood transfusion. Sera were analyzed for immunoglobulin G-anti-HLA class I and class II antibodies by enzyme-linked immunosorbant assay, and for non-organ-specific autoantibodies (antinuclear, anti-smooth muscle, anti-mitochondrial and anti-liver/kidney microsomes type 1 antibodies) using indirect immunofluorescence technique. Circulating anti-HLA class I and class II antibodies were detected in 15/67 (22.4 %) and 11/67 (16.4 %) respectively, while none of normal controls had detectable anti-HLA antibodies in the serum. The frequency of detecting anti-HLA antibodies was significantly higher in patients with elevated serum ALT than persistently normal serum ALT values (31.6 % vs 10.3 %; P = 0.039) and was associated with non-organ-specific serum autoantibodies in 11/15 (73.3 %) patients. Those with circulating anti-HLA antibodies had significantly higher levels of serum aminotransferases, gamma-glutamyl transpeptidase, viral load and necroinflammatory and fibrosis scores in liver biopsies than patients with negative anti-HLA antibody (P < 0.001). In conclusions, the presence of circulating antibodies against HLA class I and class II molecules in HCV antibodies may represent an autoimmune response to HLA antigens and may play a pathogenetic role in the induction of the HCV-related chronic liver disease.