Periodic fever, aphthous stomatitis, pharyngitis, cervical adenitis syndrome is linked to dysregulated monocyte IL-1β production.

Détails

ID Serval
serval:BIB_26BE6652A4D0
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Institution
Titre
Periodic fever, aphthous stomatitis, pharyngitis, cervical adenitis syndrome is linked to dysregulated monocyte IL-1β production.
Périodique
The Journal of allergy and clinical immunology
Auteur(s)
Kolly L., Busso N., von Scheven-Gete A., Bagnoud N., Moix I., Holzinger D., Simon G., Ives A., Guarda G., So A., Morris M.A., Hofer M.
ISSN
1097-6825 (Electronic)
ISSN-L
0091-6749
Statut éditorial
Publié
Date de publication
06/2013
Peer-reviewed
Oui
Volume
131
Numéro
6
Pages
1635-1643
Langue
anglais
Notes
Publication types: Journal Article ; Research Support, Non-U.S. Gov't
Publication Status: ppublish
Résumé
The exact pathogenesis of the pediatric disorder periodic fever, aphthous stomatitis, pharyngitis, cervical adenitis (PFAPA) syndrome is unknown.
We hypothesized that PFAPA might be due to dysregulated monocyte IL-1β production linked to genetic variants in proinflammatory genes.
Fifteen patients with PFAPA syndrome were studied during and outside a febrile episode. Hematologic profile, inflammatory markers, and cytokine levels were measured in the blood. The capacity of LPS-stimulated PBMCs and monocytes to secrete IL-1β was assessed by using ELISA, and active IL-1β secretion was visualized by means of Western blotting. Real-time quantitative PCR was performed to assess cytokine gene expression. DNA was screened for variants of the MEFV, TNFRSF1A, MVK, and NLRP3 genes in a total of 57 patients with PFAPA syndrome.
During a febrile attack, patients with PFAPA syndrome revealed significantly increased neutrophil counts, erythrocyte sedimentation rates, and C-reactive protein, serum amyloid A, myeloid-related protein 8/14, and S100A12 levels compared with those seen outside attacks. Stimulated PBMCs secreted significantly more IL-1β during an attack (during a febrile episode, 575 ± 88 pg/mL; outside a febrile episode, 235 ± 56 pg/mL; P < .001), and this was in the mature active p17 form. IL-1β secretion was inhibited by ZYVAD, a caspase inhibitor. Similar results were found for stimulated monocytes (during a febrile episode, 743 ± 183 pg/mL; outside a febrile episode, 227 ± 92 pg/mL; P < .05). Genotyping identified variants in 15 of 57 patients, with 12 NLRP3 variants, 1 TNFRSF1A variant, 4 MEFV variants, and 1 MVK variant.
Our data strongly suggest that IL-1β monocyte production is dysregulated in patients with PFAPA syndrome. Approximately 20% of them were found to have NLRP3 variants, suggesting that inflammasome-related genes might be involved in this autoinflammatory syndrome.
Mots-clé
Adolescent, Adult, Aged, Child, Female, Fever/genetics, Fever/immunology, Fever/metabolism, Genetic Variation, Humans, Inflammation/immunology, Inflammation/metabolism, Inflammation Mediators/blood, Interleukin 1 Receptor Antagonist Protein/metabolism, Interleukin-1beta/biosynthesis, Leukocyte Count, Leukocytes, Mononuclear/immunology, Leukocytes, Mononuclear/metabolism, Lipopolysaccharides/immunology, Lymphadenitis/genetics, Lymphadenitis/immunology, Lymphadenitis/metabolism, Male, Middle Aged, Monocytes/immunology, Monocytes/metabolism, Neutrophils, Pharyngitis/genetics, Pharyngitis/immunology, Pharyngitis/metabolism, Stomatitis, Aphthous/genetics, Stomatitis, Aphthous/immunology, Stomatitis, Aphthous/metabolism, Syndrome, Young Adult
Pubmed
Web of science
Création de la notice
17/01/2013 8:54
Dernière modification de la notice
03/05/2020 6:02
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