| Periodic fever, aphthous stomatitis, pharyngitis, and adenitis (PFAPA) is a disorder of innate immunity and Th1 activation responsive to IL-1 blockade. | |
| | |
MedLine Citation:
|
PMID: 21478439 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
|
The syndrome of periodic fever, aphthous stomatitis, pharyngitis, and cervical adenitis (PFAPA) is the most common periodic fever disease in children. However, the pathogenesis is unknown. Using a systems biology approach we analyzed blood samples from PFAPA patients whose genetic testing excluded hereditary periodic fevers (HPFs), and from healthy children and pediatric HPF patients. Gene expression profiling could clearly distinguish PFAPA flares from asymptomatic intervals, HPF flares, and healthy controls. During PFAPA attacks, complement (C1QB, C2, SERPING1), IL-1-related (IL-1B, IL-1RN, CASP1, IL18RAP), and IFN-induced (AIM2, IP-10/CXCL10) genes were significantly overexpressed, but T cell-associated transcripts (CD3, CD8B) were down-regulated. On the protein level, PFAPA flares were accompanied by significantly increased serum levels of chemokines for activated T lymphocytes (IP-10/CXCL10, MIG/CXCL9), G-CSF, and proinflammatory cytokines (IL-18, IL-6). PFAPA flares also manifested a relative lymphopenia. Activated CD4(+)/CD25(+) T-lymphocyte counts correlated negatively with serum concentrations of IP-10/CXCL10, whereas CD4(+)/HLA-DR(+) T lymphocyte counts correlated positively with serum concentrations of the counterregulatory IL-1 receptor antagonist. Based on the evidence for IL-1β activation in PFAPA flares, we treated five PFAPA patients with a recombinant IL-1 receptor antagonist. All patients showed a prompt clinical and IP-10/CXCL10 response. Our data suggest an environmentally triggered activation of complement and IL-1β/-18 during PFAPA flares, with induction of Th1-chemokines and subsequent retention of activated T cells in peripheral tissues. IL-1 inhibition may thus be beneficial for treatment of PFAPA attacks, with IP-10/CXCL10 serving as a potential biomarker. |
| | |
Authors:
|
Silvia Stojanov; Sivia Lapidus; Puja Chitkara; Henry Feder; Juan C Salazar; Thomas A Fleisher; Margaret R Brown; Kathryn M Edwards; Michael M Ward; Robert A Colbert; Hong-Wei Sun; Geryl M Wood; Beverly K Barham; Anne Jones; Ivona Aksentijevich; Raphaela Goldbach-Mansky; Balu Athreya; Karyl S Barron; Daniel L Kastner |
Related Documents
:
|
14594189 - Pathophysiological aspects of cellular pyridine nucleotide metabolism: focus on the vas... 12826269 - Immunosuppressant pg490 (triptolide) induces apoptosis through the activation of caspas... 19410639 - Pro-apoptotic effects of nivalenol and deoxynivalenol trichothecenes in j774a.1 murine ... 15132839 - Oridonin induces apoptosis of hela cells via altering expression of bcl-2/bax and activ... 21673659 - A yeast bh3-only protein mediates the mitochondrial pathway of apoptosis. 8637709 - Bcl-2 and adenovirus e1b 19 kda protein prevent e1a-induced processing of cpp32 and cle... 21391459 - Immune regulation by dendritic cells and t cells--basic science, diagnostic, and clinic... 22542939 - Effect of pander in βtc6-cell lipoapoptosis and the protective role of exendin-4. 21602309 - Inactivation of tautomerase activity of macrophage migration inhibitory factor by sulfo... |
Publication Detail:
|
Type: Clinical Trial; Journal Article; Multicenter Study; Research Support, N.I.H., Extramural; Research Support, N.I.H., Intramural Date: 2011-04-08 |
Journal Detail:
|
Title: Proceedings of the National Academy of Sciences of the United States of America Volume: 108 ISSN: 1091-6490 ISO Abbreviation: Proc. Natl. Acad. Sci. U.S.A. Publication Date: 2011 Apr |
Date Detail:
|
Created Date: 2011-04-27 Completed Date: 2011-06-24 Revised Date: 2011-10-26 |
Medline Journal Info:
|
Nlm Unique ID: 7505876 Medline TA: Proc Natl Acad Sci U S A Country: United States |
Other Details:
|
Languages: eng Pagination: 7148-53 Citation Subset: IM |
Affiliation:
|
National Institute of Arthritis and Musculoskeletal and Skin Diseases, National Institutes of Health, Bethesda, MD 20892, USA. |
| Data Bank Information | |
Bank Name/Acc. No.:
|
GEO/GSE17732 |
Export Citation:
|
APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
|
Adolescent Child Child, Preschool Cytokines / immunology, metabolism Female Fever / immunology*, metabolism, therapy Gene Expression Profiling Gene Expression Regulation / immunology Humans Immunity, Innate* Interleukin-1 / antagonists & inhibitors, immunology*, metabolism Lymphadenitis / immunology*, metabolism, therapy Lymphocyte Activation / immunology* Male Pharyngitis / immunology*, metabolism, therapy Stomatitis, Aphthous / immunology, metabolism, therapy Th1 Cells / immunology* |
| Chemical | |
Reg. No./Substance:
|
0/Cytokines; 0/Interleukin-1 |
| Comments/Corrections | |
Comment In:
|
Proc Natl Acad Sci U S A. 2011 Aug 23;108(34):E525
[PMID:
21810991
]
|
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
Previous Document: Large-scale characterization of peptide-MHC binding landscapes with structural simulations.
Next Document: Multilevel control of Arabidopsis 3-hydroxy-3-methylglutaryl coenzyme A reductase by protein phospha...