Background Recent observations in large and well established familial Mediterranean fever (FMF) cohorts suggested a lower than expected prevalence for SLE and SLE patients carriers for the common MEFV mutations were found to have more frequent febrile episodes and pleurisy whereas renal complications seemed to be rare.(1,2)
Objectives Our aim was to investigate the prevalence of MEFV gene mutations in patients with SLE and their effect on organ involvement in a well-defined group of SLE nephritis patients.
Methods Carrier frequencies of MEFV gene mutations (M694V, M680I, V726A and E148Q) were investigated in 111 SLE patients (102 females, 9 males, mean age 40.7±13.1 years [median age 39, min–max: 19 – 82]) using PCR-restriction fragment length polymorphism analysis.
Disease severity was defined by the presence of biopsy proven SLE nephritis (SLE-Gn). Mild-SLE group consisted patients with systemic manifestations such as skin-, musculoskeletal-, and serosal involvement and mild cytopenias.None of the SLE patients were fulfilling the revised Tel-Hashomer criteria.
One hundered and eighty six blood donors were enrolled as controls. (n=186, M/F 88/98, mean age 54.5±12.2).
Results Carrier frequency for the MEFV gene mutations under study was 14.4% in SLE patients and 18.8% in controls (p=0.34). After the exclusion of the less penetrant E148Q variation, re-analysis revealed an association between exon 10 mutations and SLE nephritis [p =0.050, odds ratio (OR) 4.16, 95% confidence interval (CI) 1.04–16.6]. Carrier rate for the E148Q mutation decreased in the SLE group (controls vs. SLE=20/186 vs. 4/111, p=0.03) and E148Q mutation was absent in SLE nephritis (controls vs. SLE nephritis=20/186 vs. 0/47, p=0.016, OR=11.69, 95% CI=0.69-197.13).
Conclusions Carrier rate of the studied MEFV mutations was slightly lower in the SLE group, which is in parallel with previous observations that FMF may confer some protection from SLE. Interestingly, Exon 10 mutations were associated with SLE nephritis only after the exclusion of the E148Q mutation. The significance of the E148Q as a disease causing mutation is still controversial.(3,4) Strikingly, the E148Q mutation disappeared with SLE disease severity while its carrier rate was 10.7% in controls. Until now, E148Q mutation was evaluated on the basis of its similar frequency in FMF and control groups and by the presence of healthy subjects homozygous for this mutation. Whether E148Q is a polymorphism generally affecting inflammatory pathways is not tested, yet. The only study, dealing with this issue reports an association with longevity and E148Q mutation.(5)
In this regard, absence of the E148Q mutation in SLE nephritis may serve as a clue for further investigation on its role as a general modulatory polymorphism for inflammation. This clarification is necessary to conclude whether other more penetrant MEFV gene mutations confer susceptibility to nephritis in SLE.
Lidar M. et-al. Lupus. 2008 Jul;17(7):663-9.
Shinar Y. et-al. Lupus. 2012 Aug;21(9):993-8.
Tchernitchko D. et-al. Hum Mutat. 2003 Oct;22(4):339-40.
Ben-Chetrit et-al. Hum Mutat. 2000 Apr;15(4):385-6.
Lidar et-al. Immunol Res. 2013 Jul;56(2-3):371-5.
Disclosure of Interest : None declared