Evolution and long-term outcomes of combined immunodeficiency due to CARMIL2 deficiency.
Обработка статьи · этапы, ошибки и управление
Ошибки и ограничения
История · было → стало
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Kolukisa Burcu, Baser Dilek, Akcam Bengu, Danielson Jeffrey, Bilgic Eltan Sevgi, Haliloglu Yesim, Sefer Asena Pinar, Babayeva Royale, Akgun Gamze, Charbonnier Louis-Marie, Schmitz-Abe Klaus, Kendir Demirkol Yasemin, Zhang Yu, Gonzaga-Jauregui Claudia, Jimenez Heredia Raul, Kasap Nurhan, Kiykim Ayca, Ozek Yucel Esra, Gok Veysel, Unal Ekrem, Pac Kisaarslan Aysenur, Nepesov Serdar, Baysoy Gokhan, Onal Zerrin, Yesil Gozde, Celkan Tulin Tiraje, Cokugras Haluk, Camcioglu Yildiz, Eken Ahmet, Boztug Kaan, Lo Bernice, Karakoc-Aydiner Elif, Su Helen C, Ozen Ahmet, Chatila Talal A, Baris Safa
Аннотация
METHODS: The presenting phenotypes, long-term outcomes, and treatment responses were evaluated prospectively in 15 CARMIL2-deficient patients, including 13 novel cases. Lymphocyte subpopulations, protein expression, regulatory T (Treg), and circulating T follicular helper (cTFH ) cells were analyzed. Three-dimensional (3D) migration assay was performed to determine T-cell shape.
RESULTS: Mean age at disease onset was 38 ± 23 months. Main clinical features were skin manifestations (n = 14, 93%), failure to thrive (n = 10, 67%), recurrent infections (n = 10, 67%), allergic symptoms (n = 8, 53%), chronic diarrhea (n = 4, 27%), and EBV-related leiomyoma (n = 2, 13%). Skin manifestations ranged from atopic and seborrheic dermatitis to psoriasiform rash. Patients had reduced proportions of memory CD4+ T cells, Treg, and cTFH cells. Memory B and NK cells were also decreased. CARMIL2-deficient T cells exhibited reduced T-cell proliferation and cytokine production following CD28 co-stimulation and normal morphology when migrating in a high-density 3D collagen gel matrix. IBD was the most severe clinical manifestation, leading to growth retardation, requiring multiple interventional treatments. All patients were alive with a median follow-up of 10.8 years (range: 3-17 years).
CONCLUSION: This cohort provides clinical and immunological features and long-term follow-up of different manifestations of CARMIL2 deficiency.