{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,4]],"date-time":"2026-09-04T19:50:08Z","timestamp":1788551408615,"version":"build-2803163510"},"reference-count":48,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2021,7,30]],"date-time":"2021-07-30T00:00:00Z","timestamp":1627603200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100004410","name":"T\u00fcrkiye Bilimsel ve Teknolojik Ara\u015ftirma Kurumu","doi-asserted-by":"publisher","award":["318S202"],"award-info":[{"award-number":["318S202"]}],"id":[{"id":"10.13039\/501100004410","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["R01AI065617"],"award-info":[{"award-number":["R01AI065617"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["R01AI128976"],"award-info":[{"award-number":["R01AI128976"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Allergy"],"published-print":{"date-parts":[[2022,3]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>Biallelic loss\u2010of\u2010function mutations in <jats:italic>CARMIL2<\/jats:italic> cause combined immunodeficiency associated with dermatitis, inflammatory bowel disease (IBD), and EBV\u2010related smooth muscle tumors. Clinical and immunological characterizations of the disease with long\u2010term follow\u2010up 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\u2010term efficacy of treatment in controlling different disease manifestations.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>The presenting phenotypes, long\u2010term outcomes, and treatment responses were evaluated prospectively in 15 CARMIL2\u2010deficient patients, including 13 novel cases. Lymphocyte subpopulations, protein expression, regulatory T (Treg), and circulating T follicular helper (cT<jats:sub>FH<\/jats:sub>) cells were analyzed. Three\u2010dimensional (3D) migration assay was performed to determine T\u2010cell shape.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Mean age at disease onset was 38\u00a0\u00b1\u00a023\u00a0months. Main clinical features were skin manifestations (<jats:italic>n<\/jats:italic>\u00a0=\u00a014, 93%), failure to thrive (<jats:italic>n<\/jats:italic>\u00a0=\u00a010, 67%), recurrent infections (<jats:italic>n<\/jats:italic>\u00a0=\u00a010, 67%), allergic symptoms (<jats:italic>n<\/jats:italic>\u00a0=\u00a08, 53%), chronic diarrhea (<jats:italic>n<\/jats:italic>\u00a0=\u00a04, 27%), and EBV\u2010related leiomyoma (<jats:italic>n<\/jats:italic>\u00a0=\u00a02, 13%). Skin manifestations ranged from atopic and seborrheic dermatitis to psoriasiform rash. Patients had reduced proportions of memory CD4<jats:sup>+<\/jats:sup> T cells, Treg, and cT<jats:sub>FH<\/jats:sub> cells. Memory B and NK cells were also decreased. CARMIL2\u2010deficient T cells exhibited reduced T\u2010cell proliferation and cytokine production following CD28 co\u2010stimulation and normal morphology when migrating in a high\u2010density 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\u2010up of 10.8\u00a0years (range: 3\u201317\u00a0years).<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>This cohort provides clinical and immunological features and long\u2010term follow\u2010up of different manifestations of CARMIL2 deficiency.<\/jats:p><\/jats:sec>","DOI":"10.1111\/all.15010","type":"journal-article","created":{"date-parts":[[2021,7,20]],"date-time":"2021-07-20T13:56:23Z","timestamp":1626789383000},"page":"1004-1019","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":51,"title":["Evolution and long\u2010term outcomes of combined immunodeficiency due to CARMIL2 deficiency"],"prefix":"10.1111","volume":"77","author":[{"given":"Burcu","family":"Kolukisa","sequence":"first","affiliation":[{"name":"Faculty of Medicine Pediatric Allergy and Immunology Marmara University  Istanbul Turkey"},{"name":"Istanbul Jeffrey Modell Diagnostic and Research 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