MEFV gene mutations in neuro-Behçet's disease and neuro-Sweet disease.

Keita Matsuura,Dai Kishida,Atsushi Niwa,Kei Tachibana,Yoshinori Hirata,Yamato Nishiguchi,Ai Ogawa‐Ito,Hidehiro Ishikawa,Hirofumi Matsuyama,Hidekazu Tomimoto,Yuichiro Ii,Natsuko Kato,Akihiro Shindo,Akira Taniguchi,Akane Mizutani

doi:10.1002/acn3.50937

Abstract

Mediterranean fever (MEFV) gene mutations are associated with familial Mediterranean fever (FMF). Recent studies have suggested that MEFV gene mutations may act as disease modifiers in neuro‐Behçet's (NBD) disease and neuro‐Sweet disease (NSD). We investigated MEFV genes and clinical features in 17 patients with NBD or NSD. MEFV gene mutations were frequently observed (70.6%). Headaches and exertional leg pain were associated with MEFV gene mutations (P < 0.05). Moreover, higher frequency of white matter lesions without sites predilection (P < 0.05) and non‐parenchymal lesions (P < 0.05) were also observed. MEFV gene mutations may be associated with particular findings and lesion sites.

Highlights

Neuro-Behßcet’s disease (NBD) and neuro-Sweet disease (NSD) are neurological manifestations of Behßcet’s disease (BD) and Sweet disease, respectively, with occasional serious sequelae.[1,2] Considering the overlap in their symptoms, NSD and NBD can be regarded as forms of neuroneutrophilic disease (NND), a broad-spectrum disorder caused by the hyperactivity of neutrophilic cells.[3]Genetically, class I human leukocyte antigen (HLA) serotypes have been associated with BD (e.g., HLA-B51)[4] and NSD (e.g., HLA-B54 and Cw1).[2]
magnetic resonance imaging (MRI) findings indicated that Mediterranean fever (MEFV)+ patients exhibited a higher frequency of white matter lesions without site predilection (75% vs. 20%, P = 0.036) and non-parenchymal lesions (50% vs. 0%, P = 0.049)
Patients with central nervous system (CNS) inflammation and symptoms related to NBD or NSD frequently exhibited MEFV gene mutations

Summary

Introduction

Class I human leukocyte antigen (HLA) serotypes have been associated with BD (e.g., HLA-B51)[4] and NSD (e.g., HLA-B54 and Cw1).[2] According to recent reports, mutations in the Mediterranean fever (MEFV) gene, which is associated with familial Mediterranean fever (FMF),[5] may act as disease modifiers for NBD6,7 and NSD.[8,9] FMF, an autoinflammatory disease, is characterized by recurrent episodes of fever, serositis, arthritis, and dermal manifestations.[5] BD and FMF share common symptoms, laboratory findings, and treatments.[10] Colchicine is the mainstay of FMF treatment and is one of the valid therapeutic options for BD. There may be a pathophysiological link among NBD, NSD, and FMF. Clarifying the role of MEFV gene in NBD and NSD is important for elucidating the mechanism of central nervous system (CNS) inflammation and developing treatments

Methods

Results

Conclusion