IL-17 receptor A and adenosine deaminase 2 deficiency in siblings with recurrent infections and chronic inflammation.

Détails

ID Serval
serval:BIB_D933D1DD0E0F
Type
Article: article d'un périodique ou d'un magazine.
Sous-type
Etude de cas (case report): rapporte une observation et la commente brièvement.
Collection
Publications
Titre
IL-17 receptor A and adenosine deaminase 2 deficiency in siblings with recurrent infections and chronic inflammation.
Périodique
Journal of Allergy and Clinical Immunology
Auteur(s)
Fellmann F., Angelini F., Wassenberg J., Perreau M., Arenas Ramirez N., Simon G., Boyman O., Demaria O., Christen-Zaech S., Hohl D., Belfiore M., von Scheven-Gete A., Gilliet M., Bochud P.Y., Perrin Y., Beck Popovic M., Bart P.A., Beckmann J.S., Martinet D., Hofer M.
ISSN
1097-6825 (Electronic)
ISSN-L
0091-6749
Statut éditorial
Publié
Date de publication
2016
Peer-reviewed
Oui
Volume
137
Numéro
4
Pages
1189-96.e1-2
Langue
anglais
Notes
Publication types: Case Reports
Résumé
BACKGROUND: Data on patients affected by chronic mucocutaneous candidiasis underscore the preponderant role of IL-17 receptor A (IL-17RA) in preserving mucocutaneous immunity. Little is known about the role of adenosine deaminase (ADA) 2 in regulation of immune responses, although recent reports linked ADA2 deficiency with inflammation and vasculitis.
OBJECTIVE: We sought to investigate the mechanisms of chronic inflammation and vasculitis in a child lacking IL-17RA and ADA2 to identify therapeutic targets.
METHODS: We report a family with 2 siblings who have had recurrent mucocutaneous infections with Candida albicans and Staphylococcus aureus and chronic inflammatory disease and vasculitis since early childhood, which were refractory to classical treatments. Array-based comparative genomic hybridization analysis showed that both siblings are homozygous for a 770-kb deletion on chr22q11.1 encompassing both IL17RA and cat eye critical region 1 (CECR1). Immunologic studies were carried out by means of flow cytometry, ELISA, and RIA.
RESULTS: As expected, in the affected child we found a lack of IL-17RA expression, which implies a severe malfunction in the IL-17 signaling pathway, conferring susceptibility to recurrent mucocutaneous infections. Surprisingly, we detected an in vitro and in vivo upregulation of proinflammatory cytokines, notably IL-1β and TNF-α, which is consistent with the persistent systemic inflammation.
CONCLUSIONS: This work emphasizes the utility of whole-genome analyses combined with immunologic investigation in patients with unresolved immunodeficiency. This approach is likely to provide an insight into immunologic pathways and mechanisms of disease. It also provides molecular evidence for more targeted therapies. In addition, our report further corroborates a potential role of ADA2 in modulating immunity and inflammation.
Mots-clé
Adenosine Deaminase/deficiency, Adenosine Deaminase/genetics, Adolescent, Candidiasis, Chronic Mucocutaneous/complications, Candidiasis, Chronic Mucocutaneous/genetics, Child, Child, Preschool, Chronic Disease, Comparative Genomic Hybridization, Fatal Outcome, Female, Humans, Inflammation/complications, Inflammation/genetics, Intercellular Signaling Peptides and Proteins/deficiency, Intercellular Signaling Peptides and Proteins/genetics, Receptors, Interleukin-17/deficiency, Receptors, Interleukin-17/genetics, Sequence Deletion, Siblings, Vasculitis/complications, Vasculitis/genetics
Pubmed
Web of science
Création de la notice
10/02/2016 11:49
Dernière modification de la notice
03/03/2018 21:52
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