| Contributors: |
Toubiana, J.; Okada, S.; Hiller, J.; Oleastro, M.; Lagos Gomez, M.; Aldave Becerra, J. C.; Ouachee-Chardin, M.; Fouyssac, F.; Girisha, K. M.; Etzioni, A.; Van Montfrans, J.; Camcioglu, Y.; Kerns, L. A.; Belohradsky, B.; Blanche, S.; Bousfiha, A.; Rodriguez-Gallego, C.; Meyts, I.; Kisand, K.; Reichenbach, J.; Renner, E. D.; Rosenzweig, S.; Grimbacher, B.; van de Veerdonk, F. L.; Traidl-Hoffmann, C.; Picard, C.; Marodi, L.; Morio, T.; Kobayashi, M.; Lilic, D.; Milner, J. D.; Holland, S.; Casanova, J. -L.; Puel, A; Cypowyj, S; Thumerelle, C; Toulon, A; Bustamante, J; Tahuil, N; Salhi, Dalila; Boiu, S; Chopra, C; Di Giovanni, D; Bezrodnik, L; Boutros, J; Thomas, C; Lacuesta, G; Jannier, S; Korganow, A; Paillard, C; Boutboul; Bué, M; Marie-Cardine, A; Bayart, S; Migaud, M; Weiss; Karmochkine, M; Garcia-Martinez, Jm; Stephan, Jl; Bensaid, P; Jeannoel, Gp; Witte, T; Baumann, U; Harrer, T; Navarrete, C; ACOSTA HUGHES, Benjamin; Firinu; Pignata, C; Picco, P; Mendoza, D; Lugo Reyes, So; Torres Lozano, C; Ortega-Cisneros, M; Cortina, M; Mesdaghi, M; Nabavi, M; Español, T; Martínez-Saavedra, Mt; Rezaei, N; Zoghi, S; Pac, M; Barlogis, V; Revon-Rivière, G; Haimi-Cohen, Y; Spiegel, R; Miron, D; Bouchaib, J; Blancas-Galicia, L; Toth, B; Drexel, B; Rohrlich, P; Lesens, O; Hoernes, M; Drewe, E; Abinum, M; Sawalle-Belohradsky, J; Kindle, G; Depner, M; Milani, L; Nikopensius, T |
| Description: |
Since their discovery in patients with autosomal dominant (AD) chronic mucocutaneous candidiasis (CMC) in 2011, heterozygous STAT1 gain-of-function (GOF) mutations have increasingly been identified worldwide. The clinical spectrum associated with them needed to be delineated. We enrolled 274 patients from 167 kindreds originating from 40 countries from 5 continents. Demographic data, clinical features, immunological parameters, treatment, and outcome were recorded. The median age of the 274 patients was 22 years (range, 1-71 years); 98% of them had CMC, with a median age at onset of 1 year (range, 0-24 years). Patients often displayed bacterial (74%) infections, mostly because of Staphylococcus aureus (36%), including the respiratory tract and the skin in 47% and 28% of patients, respectively, and viral (38%) infections, mostly because of Herpesviridae (83%) and affecting the skin in 32% of patients. Invasive fungal infections (10%), mostly caused by Candida spp. (29%), and mycobacterial disease (6%) caused by Mycobacterium tuberculosis, environmental mycobacteria, or Bacille Calmette-Guérin vaccines were less common. Many patients had autoimmune manifestations (37%), including hypothyroidism (22%), type 1 diabetes (4%), blood cytopenia (4%), and systemic lupus erythematosus (2%). Invasive infections (25%), cerebral aneurysms (6%), and cancers (6%) were the strongest predictors of poor outcome. CMC persisted in 39% of the 202 patients receiving prolonged antifungal treatment. Circulating interleukin-17A-producing T-cell count was low for most (82%) but not all of the patients tested. STAT1 GOF mutations underlie AD CMC, as well as an unexpectedly wide range of other clinical features, including not only a variety of infectious and autoimmune diseases, but also cerebral aneurysms and carcinomas that confer a poor prognosis. |