title: T helper 17 polarization in familial Mediterranean fever.
abstract: Autoinflammatory attacks in familial Mediterranean fever (FMF) are accompanied by elevated levels of interleukin-6 (IL-6), and are controllable by IL-1-targeting drugs. In combination, IL-6 and IL-1 are known to be potent inducers of T helper (Th) 17 cells development. Therefore, we studied the Th17 population size, and activation potential, of FMF patients. Based on the relative mRNA expression of the Th1, Th2, Treg and Th17 transcription factors T-bet, GATA3, FOXP3 and retinoic acid-related orphan receptor γT (RORγT), respectively, the Th17 population in peripheral blood mononuclear cells (PBMCs) of healthy subjects was estimated at 2.5% of the entire Th population and 4.4% in FMF patients in remission (n=6 for each group, P=0.03). IL-17 secretion after universal stimulation of the T-cell receptor in PBMCs culture was twice higher in cultures of patients with frequent attacks (n=18) than in those of patients with infrequent attacks (n=10, 1124±266 vs 615±196 pg ml(-1), P=0.009). IL-17 secretion correlated well with IL17A mRNA level. Part of the increased secretion was related to the deleterious, MEFV p.M694V homozygous genotype (n=19, 1.5-fold, P=0.03). Almost all IL-17 producer cells were CD4-positive (CD4(+)IL-17(+)). In conclusion, frequent attacks and the deleterious FMF genotype appear to drive FMF patients to a heightened Th17 response.
authors: Heller Institute of Medical Research, Sheba Medical Center, Tel Hashomer, Israel.
authors: A
authors: A
authors: Ovadia
authors: A
authors: A
authors: Livneh
authors: O
authors: O
authors: Feld
authors: I
authors: I
authors: Ben-Zvi
authors: E
authors: E
authors: Kukuy
authors: S
authors: S
authors: Kivity
authors: M
authors: M
authors: Lidar
authors: M
authors: M
authors: Barda-Saad
authors: Y
authors: Y
authors: Shinar
mesh_terms: D000293:Adolescent; D000328:Adult; D016022:Case-Control Studies; D002478:Cells, Cultured; D003598:Cytoskeletal Proteins / Q000235:genetics; D010505:Familial Mediterranean Fever / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D005260:Female; D051858:Forkhead Transcription Factors / Q000235:genetics / Q000378:metabolism; D050990:GATA3 Transcription Factor / Q000235:genetics / Q000378:metabolism; D006801:Humans; D020381:Interleukin-17 / Q000235:genetics / Q000378:metabolism; D008213:Lymphocyte Activation; D008297:Male; D008875:Middle Aged; D057094:Nuclear Receptor Subfamily 1, Group F, Member 1 / Q000235:genetics / Q000378:metabolism; D000071198:Pyrin; D050378:T-Lymphocytes, Regulatory / Q000378:metabolism; D058504:Th17 Cells / Q000276:immunology* / Q000378:metabolism; D014158:Transcription, Genetic
chemical_list: D003598:Cytoskeletal Proteins; C418974:FOXP3 protein, human; D051858:Forkhead Transcription Factors; D050990:GATA3 Transcription Factor; C494749:GATA3 protein, human; C508717:IL17A protein, human; D020381:Interleukin-17; C000604192:MEFV protein, human; D057094:Nuclear Receptor Subfamily 1, Group F, Member 1; D000071198:Pyrin