Evolution and long-term outcomes of combined immunodeficiency due to CARMIL2 deficiency.

Autor:	Kolukisa B; Faculty of Medicine, Pediatric Allergy and Immunology, Marmara University, Istanbul, Turkey.; Istanbul Jeffrey Modell Diagnostic and Research Center for Primary Immunodeficiencies, Istanbul, Turkey.; The Isil Berat Barlan Center for Translational Medicine, Istanbul, Turkey., Baser D; Faculty of Medicine, Pediatric Allergy and Immunology, Marmara University, Istanbul, Turkey.; Istanbul Jeffrey Modell Diagnostic and Research Center for Primary Immunodeficiencies, Istanbul, Turkey.; The Isil Berat Barlan Center for Translational Medicine, Istanbul, Turkey., Akcam B; Faculty of Medicine, Pediatric Allergy and Immunology, Marmara University, Istanbul, Turkey.; Istanbul Jeffrey Modell Diagnostic and Research Center for Primary Immunodeficiencies, Istanbul, Turkey.; The Isil Berat Barlan Center for Translational Medicine, Istanbul, Turkey., Danielson J; Human Immunological Diseases Section, Laboratory of Clinical Immunology and Microbiology, NIAID, NIH, Bethesda, Maryland, USA.; Clinical Genomics Program, NIAID, NIH, Bethesda, Maryland, USA., Bilgic Eltan S; Faculty of Medicine, Pediatric Allergy and Immunology, Marmara University, Istanbul, Turkey.; Istanbul Jeffrey Modell Diagnostic and Research Center for Primary Immunodeficiencies, Istanbul, Turkey.; The Isil Berat Barlan Center for Translational Medicine, Istanbul, Turkey., Haliloglu Y; Department of Medical Biology, Erciyes University School of Medicine, Kayseri, Turkey., Sefer AP; Faculty of Medicine, Pediatric Allergy and Immunology, Marmara University, Istanbul, Turkey.; Istanbul Jeffrey Modell Diagnostic and Research Center for Primary Immunodeficiencies, Istanbul, Turkey.; The Isil Berat Barlan Center for Translational Medicine, Istanbul, Turkey., Babayeva R; Faculty of Medicine, Pediatric Allergy and Immunology, Marmara University, Istanbul, Turkey.; Istanbul Jeffrey Modell Diagnostic and Research Center for Primary Immunodeficiencies, Istanbul, Turkey.; The Isil Berat Barlan Center for Translational Medicine, Istanbul, Turkey., Akgun G; Faculty of Medicine, Pediatric Allergy and Immunology, Marmara University, Istanbul, Turkey.; Istanbul Jeffrey Modell Diagnostic and Research Center for Primary Immunodeficiencies, Istanbul, Turkey.; The Isil Berat Barlan Center for Translational Medicine, Istanbul, Turkey., Charbonnier LM; Boston Children's Hospital and Department of Pediatrics, Division of Immunology, Harvard Medical School, Boston, Massachusetts, USA., Schmitz-Abe K; Boston Children's Hospital, Division of Immunology and Newborn Medicine, Harvard Medical School, Boston, Massachusetts, USA., Kendir Demirkol Y; Genomic Laboratory (GLAB), Umraniye Teaching and Research Hospital, University of Health Sciences, Istanbul, Turkey., Zhang Y; Human Immunological Diseases Section, Laboratory of Clinical Immunology and Microbiology, NIAID, NIH, Bethesda, Maryland, USA.; Clinical Genomics Program, NIAID, NIH, Bethesda, Maryland, USA., Gonzaga-Jauregui C; Regeneron Genetics Center, Tarrytown, New York, USA., Jimenez Heredia R; Ludwig Boltzmann Institute for Rare and Undiagnosed Diseases, Vienna, Austria.; St. Anna Children's Cancer Research Institute (CCRI), Vienna, Austria., Kasap N; Faculty of Medicine, Pediatric Allergy and Immunology, Marmara University, Istanbul, Turkey.; Istanbul Jeffrey Modell Diagnostic and Research Center for Primary Immunodeficiencies, Istanbul, Turkey.; The Isil Berat Barlan Center for Translational Medicine, Istanbul, Turkey., Kiykim A; Faculty of Medicine, Pediatric Allergy and Immunology, Istanbul University-Cerrahpasa, Istanbul, Turkey., Ozek Yucel E; Istanbul Faculty of Medicine, Pediatric Allergy and Immunology, Istanbul University, Istanbul, Turkey., Gok V; Erciyes University School of Medicine, Pediatric Hematology and Oncology, Kayseri, Turkey., Unal E; Erciyes University School of Medicine, Pediatric Hematology and Oncology, Kayseri, Turkey., Pac Kisaarslan A; Erciyes University School of Medicine, Pediatric Rheumatology, Kayseri, Turkey., Nepesov S; Department of Pediatric Allergy and Immunology, Medipol University Medical Faculty, Istanbul, Turkey., Baysoy G; Department of Pediatric Gastroenterology, Medipol University Medical Faculty, Istanbul, Turkey., Onal Z; Department of Pediatric Gastroenterology, Hepatology and Nutrition, Istanbul Faculty of Medicine, Istanbul University, Istanbul, Turkey., Yesil G; Department of Medical Genetics, Istanbul Faculty of Medicine, Istanbul University, Istanbul, Turkey., Celkan TT; Faculty of Medicine, Division of Pediatric Hematology and Oncology, Istanbul University-Cerrahpasa, Istanbul, Turkey., Cokugras H; Faculty of Medicine, Pediatric Allergy and Immunology, Istanbul University-Cerrahpasa, Istanbul, Turkey., Camcioglu Y; Faculty of Medicine, Pediatric Allergy and Immunology, Istanbul University-Cerrahpasa, Istanbul, Turkey., Eken A; Department of Medical Biology, Erciyes University School of Medicine, Kayseri, Turkey., Boztug K; Ludwig Boltzmann Institute for Rare and Undiagnosed Diseases, Vienna, Austria.; St. Anna Children's Cancer Research Institute (CCRI), Vienna, Austria., Lo B; Research Branch, Division of Translational Medicine, Sidra Medicine, Doha, Qatar.; College of Health and Life Sciences, Hamad Bin Khalifa University, Doha, Qatar., Karakoc-Aydiner E; Faculty of Medicine, Pediatric Allergy and Immunology, Marmara University, Istanbul, Turkey.; Istanbul Jeffrey Modell Diagnostic and Research Center for Primary Immunodeficiencies, Istanbul, Turkey.; The Isil Berat Barlan Center for Translational Medicine, Istanbul, Turkey., Su HC; Human Immunological Diseases Section, Laboratory of Clinical Immunology and Microbiology, NIAID, NIH, Bethesda, Maryland, USA.; Clinical Genomics Program, NIAID, NIH, Bethesda, Maryland, USA., Ozen A; Faculty of Medicine, Pediatric Allergy and Immunology, Marmara University, Istanbul, Turkey.; Istanbul Jeffrey Modell Diagnostic and Research Center for Primary Immunodeficiencies, Istanbul, Turkey.; The Isil Berat Barlan Center for Translational Medicine, Istanbul, Turkey., Chatila TA; Boston Children's Hospital and Department of Pediatrics, Division of Immunology, Harvard Medical School, Boston, Massachusetts, USA., Baris S; Faculty of Medicine, Pediatric Allergy and Immunology, Marmara University, Istanbul, Turkey.; Istanbul Jeffrey Modell Diagnostic and Research Center for Primary Immunodeficiencies, Istanbul, Turkey.; The Isil Berat Barlan Center for Translational Medicine, Istanbul, Turkey.
Jazyk:	angličtina
Zdroj:	Allergy [Allergy] 2022 Mar; Vol. 77 (3), pp. 1004-1019. Date of Electronic Publication: 2021 Jul 30.
DOI:	10.1111/all.15010
Abstrakt:	Background: Biallelic loss-of-function mutations in CARMIL2 cause combined immunodeficiency associated with dermatitis, inflammatory bowel disease (IBD), and EBV-related smooth muscle tumors. Clinical and immunological characterizations of the disease with long-term follow-up and treatment options have not been previously reported in large cohorts. We sought to determine the clinical and immunological features of CARMIL2 deficiency and long-term efficacy of treatment in controlling different disease manifestations. 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 (cT FH ) 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 cT FH 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. (© 2021 European Academy of Allergy and Clinical Immunology and John Wiley & Sons Ltd. This article has been contributed to by US Government employees and their work is in the public domain in the USA.)
Databáze:	MEDLINE
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