hereditary periodic fever periodic fever syndrome recurrent fever familial Mediterranean FMF autoinflammatory syndrome T 1 Tsutomu Oh-ishi

Transcription

1 Vol. 20 No FMFTNF TRAPS IgD HIDSCAPS FMF recurrent fever autoinflammatory syndrome T 1,2 1 1 hereditary periodic fever periodic fever syndrome 3 familial Mediterranean fever FMF 4 1 Key wordsmefv 1 Tsutomu Oh-ishi

2 adenovirus coxsackievirus Epstein Barr virus 2 A C Streptococcus Arcanobacterium haemolyticum Mycoplasma pneumoniae occult dental abscess relapsing fever FMF IgD HIDS TRAPS 3 CAPS 4 FCAS1 5 MWS 6 CINCA syndrome 7 PFAPA syndrome SLE JIA 2 CVID IgM Waldenström 1 2 recurrent fever familial Mediterranean fever MEFV 16p hyper IgD syndrome MVK 12q24 3 TNF receptor associated periodic syndrome TNFRSF1A 12p cryopyrin associated periodic syndrome CIAS1 1q44 5 familial cold autoinflammatory syndrome 1 6 Muckle Wells syndrome 7 chronic infantile neurological cutaneous and articular syndrome 8 a syndrome of periodic fever aphthous stomatitis pharyngitis adenitis EBV SLE JIA ELA Pel Ebstein fever Toll like receptor TLR inflammasome TLR pathogen associated molecular patterns PAMPspattern recogni-

3 Vol. 20 No l 1 6 5,000 mm 3 2,500 9,000 mm 3 0 7,800 mm 3 21 elastase 2 ELA2 exon 4 C4534T Pro110Leu tion receptor PRR 6 cryopyrin cryopyrin associated periodic syndrome CAPS inflammasome interleukin 1IL 1nuclear factor B NFB IL 1IL 6 IL 8 IL 12 TNF CAPS pyrin cryopyrin CIAS1 1 3 CINCA chronic infantile neurologic cutaneous and articular syndrome 2 < Muckle Wells MWS3 < familial cold autoinflammatory syndrome FCAS1 3 IgD hyper IgD syndrome HIDS MVK TNF tumor necrosis factor receptor associated periodic syndrome TRAPS 1 Tumor necrosis factor receptor 1 tumor necrosis factor receptor superfamily, number 1A TNFRSF1A TNFRSF1A TNF p55 TNFR1 TNF TNFR1 TNF

4 FMF CAPS inflammasome PYD pyrin pyrin cryopyrin pyrin apoptosis associated speck like protein ASC Cryopyrin CIAS1 ASC caspase 1 IL 1 pyrin MEFV Pyrin loss of function pyrin Cryopyrin gain of function mutation MWS FCAS1 NOMID ASC NFB NFB IL 1 interleukin 1 LRR leucine rich repeats cryopirin LRR LRR Toll like receptor TNF tumor necrosis factor MWS Muckle Wells syndrome FCAS1 familial cold autoinflammatory syndrome NOMID neonatal onset multisystemic inflammatory disease CINCA syndrome 10 NFB PFAPA periodic fever, aphthous stomatitis, pharyngitis, and cervical adenitis syndrome A C EB LPIN2 Majeed 7 Blau early onset sarcoidosis NOD2 CARD15 PAPA : PSTPIP1

5 Vol. 20 No FMF HIDS TRAPS FMF HIDS TRAPS 1 TRAPS 1 2 FMF HIDS CRP mg dl ketotifen CRP 0.43 mg dlesr 20 mm h IgE 150 U ml50 U ml 3,700 mm 3 Hb 13.3 g dl mm 3 IgG IgA IgM T 81B 10CD4 T 45CD8 T 34 CD56 NK 12 X

6 FMF 10 MEFV 16 16p FMF 8,9 MEFV 781 pyrin marenostrin 10 M694V M694I V726A M680I 2 E148Q 2 E148Q 16penetrance FMF 100 E148Q M694I M694V V726A M680I pyrin marenostrin inflammasome IL 1 NFB FMF ESR CRP A SAA 30 ESR SAA FMF 0.5 g 5 FMF 2 12 polymerase chain reaction PCRdenaturing gradient gel electrophoresis DGGE DNA MEFV PCR DNA MEFV ATG ATA M IM694I heterozygote MEFV CTG CCG L P L110P 148 GAG CAG EQ E148Q 2 heterozygote 13 1 compound hetero-

7 Vol. 20 No FMF FMF zygote FMF 4 FMF genotype M694V homozygote M694I homozygote 13,14 6 FMF mg kg 2 mg mg mg mg mg FMF MEFV M694I heterozygote FMF MEFV L110P E148Q 2 heterozygote 13 1 compound heterozygote FMF 8 FMF 20 MEFV MEFV MEFV 11,17,18

8 MEFV DNA 3 FMF FMF 4 MEFV FMF cdna pyrin FMF TRAPS TNFRSF1A TNFR1 19,20 IgD PFAPA Ting JPY, Kastner DL, Hoffman HM Caterpillers, pyrin and hereditary immunological disorders. Nat Rev Immunol , , Drenth J PH, van der Meer JWM Hereditary periodic fever. N Engl J Med , John CC, Gilsdorf JR Recurrent fever in children. Pediatr Infect Dis J , Good GR, DiNubile MJ Cyclic Fever in Hodgkin s Disease Pel Ebstein Fever. N Engl J Med , Martinon F, Tschopp J Inflammatory caspase linking an intracellular innate immune system to autoinflammatory diseases. Cell , Ferguson PJ, Chen S, Tayeh MK, et al Homozygous mutations in LPIN2 are responsible for the syndrome of chronic recurrent multifocal osteomyelitis and congenital dyserythropoietic anaemia Majeed syndrome. J Med Genet , The international FMF consortium. Ancient missense mutations in a new member of the RoRet gene family are likely to cause familial Mediterranean fever. Cell , The French FMF consortium A candidate gene for familial Mediterranean fever. Nat Genet , Gedalia A Hereditary periodic fever syndromes. Nelson textbook of pediatrics, 18th ed Kliegman RM, et al ed, Elsevier Saunders, Philadelphia, 2007, Padeh S, Shinar Y, Pras E, et al Clinical and diagnostic value of genetic testing in 216 Israeli children with familial Mediterranean fever. J Rheumatol , Livneh A, Langevitz P, Zemer D, et al Criteria for the diagnosis of familial Mediterranean fever. Arthritis Rheum ,

9 Vol. 20 No Tomiyama N, Oshiro S, Higashiuesato Y, et al End stage renal disease associated with familial Mediterranean fever. Intern Med , Kallinich T, Haffner D, Niehues T, et al Colchicine use in children and adolescents with familial Mediterranean fever literature review and consensus statement. Pediatrics 119 e474 e483, Ben Chetrit E, Levy M Familial Mediterranean fever. Lancet , Booth DR, Gillmore JD, Lachmann HJ The genetic basis of autosomal dominant familial Mediterranean fever. QJM , Nakamura A, Yazaki M, Tokuda T, et al A Japanese patient with familial Mediterranean fever associated with compound heterozygosity for pyrin variant E148Q M694I. Intern Med , Aganna E, Hammond L, Hawkins PN, et al Heterogeneity among patients with tumor necrosis factor receptor associated periodic syndrome phenotypes. Arthritis Rheum , Infevers ISSAID infevers