Immune Dysregulation in the Tonsillar Microenvironment of Periodic Fever, Aphthous Stomatitis, Pharyngitis, Adenitis (PFAPA) Syndrome.
Adolescent
CD8-Positive T-Lymphocytes
/ immunology
Cell Line
Cellular Microenvironment
/ immunology
Child
Child, Preschool
Female
Fever
/ immunology
Humans
Infant
Inflammation
/ immunology
Lymphadenitis
/ immunology
Male
Palatine Tonsil
/ immunology
Pharyngitis
/ immunology
Stomatitis, Aphthous
/ immunology
Syndrome
Tonsillectomy
/ methods
Autoinflammation
Microbiome
Pediatrics
Periodic fever
Tonsillectomy
Journal
Journal of clinical immunology
ISSN: 1573-2592
Titre abrégé: J Clin Immunol
Pays: Netherlands
ID NLM: 8102137
Informations de publication
Date de publication:
01 2020
01 2020
Historique:
received:
12
07
2019
accepted:
24
11
2019
pubmed:
7
12
2019
medline:
12
2
2021
entrez:
7
12
2019
Statut:
ppublish
Résumé
Periodic Fever, Aphthous stomatitis, Pharyngitis and Adenitis (PFAPA) syndrome is an inflammatory disorder of childhood classically characterized by recurrent fevers, pharyngitis, stomatitis, cervical adenitis, and leukocytosis. While the mechanism is unclear, previous studies have shown that tonsillectomy can be a therapeutic option with improvement in quality of life in many patients with PFAPA, but the mechanisms behind surgical success remain unknown. In addition, long-term clinical follow-up is lacking. In our tertiary care center cohort, 62 patients with PFAPA syndrome had complete resolution of symptoms after surgery (95.3%). Flow cytometric evaluation demonstrates an inflammatory cell population, distinct from patients with infectious pharyngitis, with increased numbers of CD8+ T cells (5.9% vs. 3.8%, p < 0.01), CD19+ B cells (51% vs. 35%, p < 0.05), and CD19+CD20+CD27+CD38-memory B cells (14% vs. 7.7%, p < 0.01). Cells are primed at baseline with increased percentage of IL-1β positive cells compared to control tonsil-derived cells, which require exogenous LPS stimulation. Gene expression analysis demonstrates a fivefold upregulation in IL1RN and TNF expression in whole tonsil compared to control tonsils, with persistent activation of the NF-κB signaling pathway, and differential microbial signatures, even in the afebrile period. Our data indicates that PFAPA patient tonsils have localized, persistent inflammation, in the absence of clinical symptoms, which may explain the success of tonsillectomy as an effective surgical treatment option. The differential expression of several genes and microbial signatures suggests the potential for a diagnostic biomarker for PFAPA syndrome.
Identifiants
pubmed: 31807979
doi: 10.1007/s10875-019-00724-2
pii: 10.1007/s10875-019-00724-2
pmc: PMC7085444
mid: NIHMS1545800
doi:
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
179-190Subventions
Organisme : NICHD NIH HHS
ID : K08 HD075830
Pays : United States
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