Abstract |
In gain-of-function STAT1 mutations, chronic mucocutaneous candidiasis disease (CMCD) represents the phenotypic manifestation of a complex immunodeficiency characterized by clinical and immunological heterogeneity. We aimed to study clinical manifestations, long-term complications, molecular basis, and immune profile of patients with dominant CMCD. We identified nine patients with heterozygous mutations in STAT1, including novel amino acid substitutions (L283M, L351F, L400V). High risk of azole-resistance was observed, particularly when intermittent regimens of antifungal treatment or use of suboptimal dosage occurs. We report a case of Cryptococcosis and various bacterial and viral infections. Risk of developing bronchiectasis in early childhood or gradually evolving to chronic lung disease in adolescent or adult ages emerges. Lymphopenia is variable, likely progressing by adulthood. We conclude that continuous antifungal prophylaxis associated to drug monitoring might prevent resistance to treatment; prompt diagnosis and therapy of lung disease might control long-term progression; careful monitoring of lymphopenia-related infections might improve prognosis.
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Authors | Laura Dotta, Omar Scomodon, Rita Padoan, Silviana Timpano, Alessandro Plebani, Annarosa Soresina, Vassilios Lougaris, Daniela Concolino, Angela Nicoletti, Giuliana Giardino, Amelia Licari, Gianluigi Marseglia, Claudio Pignata, Nicola Tamassia, Fabio Facchetti, Donatella Vairo, Raffaele Badolato |
Journal | Clinical immunology (Orlando, Fla.)
(Clin Immunol)
Vol. 164
Pg. 1-9
(Mar 2016)
ISSN: 1521-7035 [Electronic] United States |
PMID | 26732859
(Publication Type: Journal Article)
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Copyright | Copyright © 2016 Elsevier Inc. All rights reserved. |
Chemical References |
- Antifungal Agents
- Azoles
- STAT1 Transcription Factor
- STAT1 protein, human
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Topics |
- Adolescent
- Adult
- Antifungal Agents
(therapeutic use)
- Autoimmunity
- Azoles
(therapeutic use)
- Bacterial Infections
(complications)
- Candidiasis, Chronic Mucocutaneous
(complications, drug therapy, genetics)
- Child
- Chronic Disease
- Cryptococcosis
(complications)
- Cryptococcus neoformans
- Drug Resistance
- Female
- Humans
- Leishmaniasis, Visceral
(complications)
- Lung Diseases
(complications, drug therapy, genetics)
- Lymphopenia
(complications)
- Male
- Middle Aged
- Mutation
- Phosphorylation
- STAT1 Transcription Factor
(genetics, metabolism)
- Virus Diseases
(complications)
- Young Adult
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