AB0988 THE ASSOCIATION BETWEEN CLINICAL FEATURES AND ANALYSIS OF MEFV GENE IN 20 JAPANESE PATIENTS WITH FAMILIAL MEDITERRANEAN FEVER (FMF)

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Background FMF is recessive systemic auto inflammatory disorder characterized by recurrent fever, peritonitis, pleuritis, pericarditis and arthritis accompanied with skin rash. Mutation of MEFV gene encoding pyrin resulted in inflammasome activation and the uncontrolled production of IL-1β. Overview of pathogenesis, clinical features and management in Japanese patients with FMF had been reported1. However, the differences of clinical features between mutated and non-mutated of MEFV still remain unclear. Objectives We have analyzed 20 Japanese patients with FMF to clarify the association between various clinical features and mutation of MEFV. Methods Genomic DNA were purified from white blood cells in 20 FMF patients, and mutated MEFV has been explored. We have analyzed MEFV, TNFRSF1A, MVK and NLRP3 genes in 20 patients with FMF. Therefore, we excluded another autoinflammatory diseases such as TNF receptor-associated syndrome (TRAPS), mevalonate kinase deficiency and cryopyrin-associated periodic syndrome. Clinical symptoms and laboratory data were analyzed around onset time. Each patient had been treated with colchicine (0.5-2 mg). Results Characteristics of Patients with FMF (13 female/7 male) were as follows; Onset time were 0-53 years old (17.5 ±12.2), and teen aged patients were most. Frequencies of clinical symptoms such as periodic fever, headache, arthralgia, abdominal pain, chest pain, myalgia, and cervical lymph nodes swelling were 20/20, 7/20, 6/20, 5/20,4/20,2/20 and 1/20, respectively (double symptoms were observed). Patients with FMF were divided to 3 groups as follows; Patients with typical compound heterozygous mutations of MEFV (E148Q/M694I) which indicated exon 10 mutation, were 3 cases (group 1). Patients with atypical mutations, except for mutations in exon 10, such as exon 1 (E84K, L110P), 2 (E148Q), 3(P369S, R408Q), 5(S503C) and 9(I591M) were 8 cases (group 2). Patients with no mutations in MEFV gene were 9 cases (group 3). There were no significant differences of age at first visiting hospital (FV), onset age of fever attack (O), duration of fever attack (D) and frequency of fever attack (FF) between group 1, group2 and group 3 ( FV: 22.3 ± 4.5, 26.8 ± 14.6 years old (yo) and 29.5 ± 8.7 yo, O: 11.6 ± 2.4 yo, 18.5 ± 13.8 yo and 18.5 ± 12.0 D: 3.0 ± 1.4 hrs, 6.3 ± 3.2 hrs, and 8.1 ± 8.5 hrs, FF: 1.2 ± 0.2/month (M), 1.2 ± 1.1/M, and 1.1 ± 0.2/M), respectively. Laboratory examinations such as WBC, CRP and serum amyloid A (SAA) were not significantly different between 3 groups. All of those patients were effective for colchicine treatment except for 2 patients in group 1 because of severe diarrhea and alopecia. Finally, 2 patients in group 1 received canakinumab treatment. Mutations of E148Q were found in 9 patients (45%). Conclusion We have examined association between clinical features and mutations of MEFV in 20 Japanese patients, suggesting no positive findings in Japanese patients with FMF. Mutations of E148Q in exon 2 were observed in 16-23 % of normal Japanese patients1, indicating that E148Q is the polymorphism or accelerating factor.