Israel Medical Association Journal

Background: Familial Mediterranean fever is an autosomal recessive disease characterized by sporadic attacks of inflammation affecting the serosal spaces. The gene associated with FMF[1] (MEFV), mainly expressed in neutrophils, was recently found to be expressed also in primary cultures of serosal origin (peritoneal and synovial fibroblasts). A C5a inhibitor, previously detected in normal serosal fluids, was recently identified in serosal cultures as well, and was found to be deficient in serosal fluids and cultures obtained from FMF patients.

Objective: To investigate the effect of colchicine (the main therapeutic agent for FMF patients) and certain inflammatory cytokines (IL-1b, TNF-a, IFN-a, IFN-g) on MEFV expression and C5a inhibitor activity in neutrophils and primary peritoneal fibroblast cultures.

Methods: Human primary peritoneal fibroblast cultures and neutrophils were studied for MEFV expression and C5a inhibitor activity, using reverse transcription-polymerase chain reaction and C5a-induced myeloperoxidase assay, respectively, in the presence and absence of colchicine and cytokines.

Results: MEFV expression in neutrophils was high and could not be induced further. Its expression in the peritoneal fibroblasts was lower than in neutrophils and could be induced using colchicine and cytokines parallel with induction of C5a inhibitor activity. Semi-quantitative RT-PCR[2] assays enabled estimation of MEFV induction by the cytokines at 10–100-fold and could not be further increased by concomitant addition of colchicine.

Conclusion: Serosal tissues, which are afflicted in FMF, express colchicine and cytokine-inducible MEFV and contain inducible C5a inhibitor activity. The relation between colchicine ability to induce MEFV and C5a inhibitor activity, and its efficacy in FMF treatment, require further investigation.

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[1] RT-PCR = reverse transcription-polymerase chain reaction

[2] FMF = familial Mediterranean fever

Background: Familial Mediterranean fever is a genetic disease in which some characteristic gene mutation have been found.

Objective: To analyze the phenotype-genotype correlations in North African Jews and Armedians with FMF.

Methods: We studied MEFV gene mutations and phenotype-genotype correlations in North African Jews and Armedians with Familial Mediterranean Fever living in France.

Results: M694V mutation was the most common mutation in Jews and in Armenians. Patients with M6801 homozygosity or M6801/M694V compound heterozygosity had a phenotype as severe as patients with M694V homozygosity.

Conclusions: This study characterizes the phenotype-genotype in specific ethnic groups of patients with FMF.

Background: Familial Mediterranean fever is a genetic disorder manifested by recurrent attacks of peritonitis, pleuritis and arthritis, and characterized by clinical, histological and laboratory evidence for localized and systemic inflammation. Colchicine treatment usually prevents the attacks and the associated inflammation. Inflammation of atherosclerosis and ischemic heart disease.

Objective: To study the effect of inflammation and its prevention on occurrence of IHD, using FMF as a model.

Methods and Patients: We studied the presence of IHD and its risk factors in 290 FMF patients aged 40 years or more, and in two control groups – 233 spouses of the FMF patients’ and 126 patients with inflammatory diseases obtained from other outpatient clinics. FMF patients were also compared with age and gender-matched individuals from the population reference data of the Israel Ministry of Health.

Results: The prevalence of IHD in FMF patients was significantly lower than in the group of controls from other outpatient clinics (15.5% vs. 30.2% P< 0.05) and comparable with their spouses (11.2%) and with the matched general population in Israel (16%).

Conclusion: These findings suggest that despite the evidence of recurrent inflammation, colchicines-treated FMF patients are not more predisposed to IHD than the normal population.