Developmental Adaptive Immune Defects Associated with STAT5B Deficiency in Three Young Siblings
| Autor: | Vivian Hwa, Ashish R Kumar, Christopher Towe, Leah Tyzinski, Sareea S Al Remeithi, Andrew Dauber, Corinne Foley, Philippe Backeljauw |
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| Rok vydání: | 2020 |
| Předmět: |
Male
animal structures T cell Immunology Autoimmunity Adaptive Immunity Article Cell Line Consanguinity Memory T Cells Immune system T-Lymphocyte Subsets Exome Sequencing STAT5 Transcription Factor medicine Humans Immunology and Allergy Genetic Association Studies B cell Immunodeficiency B-Lymphocytes business.industry Siblings Homozygote Immunologic Deficiency Syndromes Disease Management Infant food and beverages FOXP3 medicine.disease Acquired immune system Phenotype medicine.anatomical_structure Mutation Disease Susceptibility business Memory T cell Biomarkers CD8 |
| Zdroj: | J Clin Immunol |
| ISSN: | 1573-2592 0271-9142 |
| Popis: | Patients with rare homozygous mutations in signal transducer and activator of transcription 5B (STAT5B) develop immunodeficiency resulting in chronic eczema, chronic infections, autoimmunity, and chronic lung disease. STAT5B deficient patients are typically diagnosed in the teenage years, limiting our understanding of the development of associated phenotypic immune abnormalities. We report the first detailed chronological account of post-natal immune dysfunction associated with STAT5B deficiency in humans. Annual immunophenotyping of three siblings carrying a novel homozygous nonsense mutation in STAT5B was carried out over four years between the ages of 7 months to 8 years. All three siblings demonstrated consistent B cell hyperactivity including elevated IgE levels and autoantibody production, associated with diagnoses of atopy and autoimmunity. Total T cell levels in each sibling remained normal, with regulatory T cells decreasing in the oldest sibling. Interestingly, a skewing toward memory T cells was identified, with the greatest changes in CD8(+) effector memory T cells. These results suggest an importance of STAT5B in B cell function and naïve versus memory T cell survival. Progressive dysregulation of FOXP3(+) regulatory T cells and CD8(+) memory T cell subsets reveal a crucial role of STAT5B in T cell homeostasis. The early diagnosis and focused immune evaluations of these three young STAT5B deficient siblings support an important role of STAT5B in adaptive immune development and function. |
| Databáze: | OpenAIRE |
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