Familial Mediterranean fever gene (MEFV) mutations as a modifier of systemic lupus erythematosus

Abstract

The objective of this study was to assess the prevalence of the Mediterranean FeVer (MEFV) gene mutations in systemic lupus erythematosus (SLE) patients and their effect on organ involvement, as well as disease activity and severity. The frequencies of three familial Mediterranean fever-related MEFV gene mutations (M694V, V726A and E148Q) were investigated in 70 SLE patients. Organ involvement, Systemic Lupus International Collaborating Clinics/American College of Rheumatology (SLICC/ACR) damage index and Systemic Lupus Erythematosus Disease Activity Index (SLEDAI) scores were correlated with mutation carriage. Eleven of 70 patients (15.7%) were found to carry an MEFV mutation. A single patient harbored two mutations, E148Q and V726A, without overt familial Mediterranean fever while the rest were heterozygous carriers. Four of the 11 carried an M694V mutation, four carried V726A and two carried E148Q. The majority of MEFV mutation carriers were Sephardic while non-carriers were mainly of Ashkenazi origin (72.7% vs. 45.7% and 47.4% vs. 9.1%, respectively, p = 0.02). SLE onset was significantly earlier in MEFV carriers (27.6 ± 9.7 vs. 38.2 ± 15.5 years, in carriers vs. non-carriers, p = 0.02). Hematologic and serologic parameters were comparable among mutation carriers and non-carriers. Febrile episodes were more common among MEFV mutation carriers (45.4% vs. 15.2%, p = 0.035) and there was a trend for excess episodes of pleuritis as well (54.5% vs. 23.7%, p = 0.06 in carriers vs. non-carriers, respectively). The frequency of secondary anti-phospholipid antibody syndrome was equivalent among the groups. Conversely, compound urinary abnormalities and renal failure was not observed among MEFV carriers yet was present in 33.4% and 18.6% of non-carriers (p = 0.027 and 0.19, respectively). SLICC damage index and SLEDAI activity index did not differ significantly between the groups. MEFV mutation carriage appears to modify the SLE disease phenotype in that it contributes to an excess of inflammatory manifestations such as fever and pleuritis on the one hand, while thwarting more severe renal involvement on the other.

The importance of M694V mutation in systemic lupus erythematosus; implications for its role in neutrophil extracellular traps associated renal involvement

“…However, the modifying role of M694V mutation on the clinical manifestation of SLE is not supported by our results. This finding is in contrast to the study by Shinar et al (29). It may be explained by different frequency of alleles and genotypes and different penetration between populations.…”

Are systemic lupus erythematosus patients carrying MEFV gene less prone to renal involvement? Report of three cases and review of the literature

“…In a recent study, it was shown that MEFV mutation carriage contributes to an excess of inflammatory manifestations such as fever and pleuritis while protecting from more severe renal involvement. 9 In conclusion, FMF and SLE can rarely be seen together. Presence of MEFV mutation in SLE may modify disease phenotype as enhanced inflammatory episodes and attenuated renal manifestations.…”

“…20 Fever and serosal involvement in FMF usually subside within 1-3 d while they are more prolonged in SLE. 9 These common findings may cause difficulties in differential diagnosis of two diseases.…”

“…[5][6][7][8] Also, SLE patients carrying a MEFV gene mutation were shown to have milder symptoms and less severe renal involvement recently. 9 Therefore, we described three patients with SLE and FMF based on clinical symptoms and genetic evaluation.…”

MEditerranean FeVer ( MEFV ) gene mutations in glomerulonephritides: a clinicopathological study

“…SLE, which is characterized primarily by overactivation of the adaptive immune system, is a good example to understand this interrelation. It is thought that FMF or the presence of MEFV gene mutations confer some protection from SLE and the two diseases rarely overlap (49), but in the case of their presence, MEFV mutations are still associated with higher disease activity indices and early onset disease (23), and exon 10 mutations with more severe disease and nephritis in patients with SLE (24). Thus, MEFV variants may potentially modify the course of glomerulonephritides not primarily mediated by IL-1β and the innate immune system like membranous nephropathy, immunoglobulin A nephropathy, and lupus nephritis.…”