1 Ocak 2022 Dergi makalesi Açık Erişim

Kolukisa, Burcu; Baser, Dilek; Akcam, Bengu; Danielson, Jeffrey; Eltan, Sevgi Bilgic; Haliloglu, Yesim; Sefer, Asena Pinar; Babayeva, Royale; Akgun, Gamze; Charbonnier, Louis-Marie; Schmitz-Abe, Klaus; Demirkol, Yasemin Kendir; Zhang, Yu; Gonzaga-Jauregui, Claudia; Heredia, Raul Jimenez; Kasap, Nurhan; Kiykim, Ayca; Yucel, Esra Ozek; Gok, Veysel; Unal, Ekrem; Unal, Ekrem

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{
  "DOI": "10.1111/all.15010", 
  "abstract": "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.", 
  "author": [
    {
      "family": "Kolukisa", 
      "given": " Burcu"
    }, 
    {
      "family": "Baser", 
      "given": " Dilek"
    }, 
    {
      "family": "Akcam", 
      "given": " Bengu"
    }, 
    {
      "family": "Danielson", 
      "given": " Jeffrey"
    }, 
    {
      "family": "Eltan", 
      "given": " Sevgi Bilgic"
    }, 
    {
      "family": "Haliloglu", 
      "given": " Yesim"
    }, 
    {
      "family": "Sefer", 
      "given": " Asena Pinar"
    }, 
    {
      "family": "Babayeva", 
      "given": " Royale"
    }, 
    {
      "family": "Akgun", 
      "given": " Gamze"
    }, 
    {
      "family": "Charbonnier", 
      "given": " Louis-Marie"
    }, 
    {
      "family": "Schmitz-Abe", 
      "given": " Klaus"
    }, 
    {
      "family": "Demirkol", 
      "given": " Yasemin Kendir"
    }, 
    {
      "family": "Zhang", 
      "given": " Yu"
    }, 
    {
      "family": "Gonzaga-Jauregui", 
      "given": " Claudia"
    }, 
    {
      "family": "Heredia", 
      "given": " Raul Jimenez"
    }, 
    {
      "family": "Kasap", 
      "given": " Nurhan"
    }, 
    {
      "family": "Kiykim", 
      "given": " Ayca"
    }, 
    {
      "family": "Yucel", 
      "given": " Esra Ozek"
    }, 
    {
      "family": "Gok", 
      "given": " Veysel"
    }, 
    {
      "family": "Unal", 
      "given": " Ekrem"
    }, 
    {
      "family": "Unal", 
      "given": " Ekrem"
    }
  ], 
  "container_title": "ALLERGY", 
  "id": "235246", 
  "issue": "3", 
  "issued": {
    "date-parts": [
      [
        2022, 
        1, 
        1
      ]
    ]
  }, 
  "page": "1004-1019", 
  "title": "Evolution and long-term outcomes of combined immunodeficiency due to CARMIL2 deficiency", 
  "type": "article-journal", 
  "volume": "77"
}