Novel STAT3 Mutation Causing Hyper-IgE Syndrome: Studies of the Clinical Course and Immunopathology

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• 作者：Mikael Sundin (1) (11) (4)
  Bianca Tesi (5) (6)
  Maria Sund B?hme (2)
  Yenan T. Bryceson (7)
  Katrin Pütsep (8)
  Samuel C. Chiang (7)
  Sarah Thunberg (3) (9)
  Jacek Winiarski (1) (4)
  Ann-Charlotte Wikstr?m (10) (3)
  
• 关键词：Job’s Syndrome ; immunodeficiency ; Th17
• 刊名：Journal of Clinical Immunology
• 出版年：2014
• 出版时间：May 2014
• 年：2014
• 卷：34
• 期：4
• 页码：469-477
• 全文大小：
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• 作者单位：Mikael Sundin (1) (11) (4)
  Bianca Tesi (5) (6)
  Maria Sund B?hme (2)
  Yenan T. Bryceson (7)
  Katrin Pütsep (8)
  Samuel C. Chiang (7)
  Sarah Thunberg (3) (9)
  Jacek Winiarski (1) (4)
  Ann-Charlotte Wikstr?m (10) (3)
  
  1. Hematology/Immunology/SCT Section, Astrid Lindgren Children’s, Karolinska University Hospital, Stockholm, Sweden
  11. Astrid Lindgren Children’s Hospital, B57, Karolinska University Hospital Huddinge, SE-141 86, Stockholm, Sweden
  4. Division of Pediatrics, Department of Clinical Science, Intervention and Technology, Karolinska Institutet, Stockholm, Sweden
  5. Childhood Cancer Research Unit, Department of Women’s and Children’s Health, Karolinska Institutet, Stockholm, Sweden
  6. Clinical Genetics Unit, Department of Molecular Medicine and Surgery, Karolinska Institutet, Stockholm, Sweden
  2. Department of Dermatology and Venereology, Karolinska University Hospital, Stockholm, Sweden
  7. Center for Infectious Medicine, Department of Medicine, Karolinska Institutet, Stockholm, Sweden
  8. Department of Microbiology, Tumor- and Cell Biology, Karolinska Institutet, Stockholm, Sweden
  3. Department of Clinical Immunology, Karolinska University Laboratory, Karolinska University Hospital, Stockholm, Sweden
  9. Divison of Clinical Immunology and Transfusion Medicine, Department of Laboratory Medicine, Karolinska Institutet, Stockholm, Sweden
  10. Department of Biosciences and Nutrition, Karolinska Institutet, Stockholm, Sweden
  
• ISSN：1573-2592

文摘

Purpose Reporting a clinical case with a novel mutation in the signal transducer and activator of transcription 3 (STAT3) gene resulting in autosomal dominant hyper-immunoglobulin E syndrome (AD-HIES). Here we also had the opportunity to perform in-depth immunologic investigations to further understand the immunopathology of this primary immunodeficiency. Methods The patient, a baby boy, was clinically assessed according to the scoring system developed by Grimbacher et al. and STAT3 was investigated by DNA sequencing. Immunologic work-up consisted of lymphocyte phenotyping and proliferation assays, measurement of soluble mediators and routine investigations. Results According to the Grimbacher score the patient was likely to have AD-HIES and a novel heterozygous STAT3 mutation (c.1110-3C>A), causing a splice error, was identified. Lymphocyte phenotyping revealed decreased numbers of interleukin (IL)-17 producing T-helper lymphocytes and aberrant B-lymphocyte subsets. Proliferative in vitro lymphocyte responses against C. albicans, staphylococcal enterotoxins and pokeweed mitogen were supernormal at presentation, whereas only the elevated response to pokeweed mitogen persisted. The soluble mediators IL?, ?0, ?2, ?3, ?5 and granulocyte colony stimulatory factor were elevated in serum. Conclusion A novel heterozygous STAT3 mutation causing defective splicing of exon 12 was identified. Lymphocyte phenotyping revealed deranged subpopulations. Despite the clinical picture with severe C. albicans and staphylococcal infections, the patient’s lymphocytes mounted responses to these pathogens. The hypereosinophilia and high immunoglobulin E levels might partly be explained by elevated IL? and ?3 as a result of lack of negative feedback from defective STAT3 signaling.