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T helper 17 polarization in familial Mediterranean fever

Genes & Immunity volume 14, pages 212–216 (2013)Cite this article

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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.

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Acknowledgements

We thank Dr Itamar Goldstein for invaluable discussions. This study was supported by a grant devoted to the memory of Johana Feler and her family members who perished in the Holocaust.

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Authors and Affiliations

  1. Heller Institute of Medical Research, Sheba Medical Center, Tel Hashomer, Israel

    A Ovadia, A Livneh & Y Shinar

  2. The Mina and Everard Goodman Faculty of Life Sciences, Bar-Ilan University, Ramat-Gan, Israel

    A Ovadia & M Barda-Saad

  3. Department of Medicine F, Sheba Medical Center, Tel Hashomer, Israel

    A Livneh, O Feld, I Ben-Zvi & M Lidar

  4. Rheumatology Unit at Zubludowitz Center for Autoimmune Diseases, Sheba Medical Center, Tel Hashomer, Israel

    A Livneh, I Ben-Zvi, S Kivity & M Lidar

  5. Sackler Faculty of Medicine, Tel Aviv University, Ramat Aviv, Israel

    A Livneh & M Lidar

  6. Department of Nephrology, Sheba Medical Center, Tel Hashomer, Israel

    E Kukuy

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  1. A Ovadia
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  2. A Livneh
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Correspondence to Y Shinar.

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Ovadia, A., Livneh, A., Feld, O. et al. T helper 17 polarization in familial Mediterranean fever. Genes Immun 14, 212–216 (2013). https://doi.org/10.1038/gene.2013.6

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