Presentation: The MEFV Gene Mutations may Increase the Risk of Pleuritis and Pericarditis in Patients with Systemic Lupus Erythematosus (2007)

812 The MEFV Gene Mutations may Increase the Risk of Pleuritis and Pericarditis in Patients with Systemic Lupus Erythematosus

PURPOSE: Systemic lupus erythematosus (SLE) is a multisystemic, autoimmune disease of unknown etiology. Different organs or tissues including the serosal membranes may be involved singly or in any combination during the chronic disease course, which is also characterized by episodic exacerbations. Familial Mediterranean Fever (FMF), an autosomal recessively inherited disorder, is characterized by recurrent, self-limited inflammatory attacks at serosal membranes and caused by mutations in the MEFV gene. The prevalence of carriers for the MEFV mutations is quite high in Turkey, Israel and Armenia, and this may be an important factor as a genetic modifier in other inflammatory disorders. This study aimed to investigate the frequency of the MEFV mutations and their effects on the disease phenotype in patients with SLE.
METHODS: 193 consecutive SLE patients (87% female; mean age 39±12; mean disease duration 9,5±7) and 101 healthy controls of Turkish origin were studied. All patients met four or more ACR criteria for the diagnosis of SLE. All individuals were genotyped for the common MEFV mutations (M694V, M680, V726A and E148Q) in Turkish FMF patients by using polymerase chain reaction and restriction fragment lenght polymorphism.
RESULTS: The frequency of carrying a single MEFV gene mutation was 15% in patients with SLE, and it was not significantly different from the frequency in the healthy control group (10%, P = 0.23). After the exclusion of E148Q mutation, the carrier rate for the remaining three most penetrant mutations was increased in the patient group compared to controls, but the difference was not significant (9,3% for 5%; p=0.19; OR=2.0; CI=0.7-5.5). Pericarditis was observed in 16 SLE patients (8.2%) and pleural effusion was seen in 5 patients (2.6%). When we analysed the association of these 3 penetrant mutations with FMF-related serosal findings, we observed a significant assocation between the MEFV carrier state and pericarditis (p=0.024; OR=3,88; CI=1.1-13.6), and also pleural effusion (p=0.017; OR=7.02; CI=1.1-46). There was also a very significant assocation between the presence of MEFV mutations and a positive family history for FMF in the patient group (p<0.001). No correlation was found between the three penetrant mutations and abdominal pain or acute phase response (ESR and CRP). CONCLUSIONS: The carrier state for the MEFV mutations does not seem to increase the overall risk for SLE susceptibility, but it may have an effect on the SLE phenotype with an increased risk for the development of pericarditis and pleural effusion. Our findings also suggest that inflammatory pathways in SLE may not involve the inflammasome, and increased acute phase response depends on different mechanisms.

 B. Erer, None; F. Cosan, None; B. Oku, None; D. Ustek, None; O. Aral, None; A. Gul, None.