Impaired polysaccharide responsiveness without agammaglobulinaemia in three patients with hypomorphic mutations inBruton Tyrosine Kinase—No detection by newborn screening for primary immunodeficiencies
| العنوان: | Impaired polysaccharide responsiveness without agammaglobulinaemia in three patients with hypomorphic mutations inBruton Tyrosine Kinase—No detection by newborn screening for primary immunodeficiencies |
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| المؤلفون: | Uwe Kölsch, V. Wahn, Klaus Warnatz, Ulrich Baumann, Stephan Borte, Ina Harder, Myriam Ricarda Lorenz, Baerbel Keller, Renate Krüger, Klaus Schwarz, Stephan Ehl, Horst von Bernuth |
| المصدر: | Scandinavian Journal of Immunology. 91 |
| بيانات النشر: | Wiley, 2019. |
| سنة النشر: | 2019 |
| مصطلحات موضوعية: | Male, 0301 basic medicine, DNA Copy Number Variations, Genotype, Primary Immunodeficiency Diseases, DNA Mutational Analysis, Immunology, Immunophenotyping, 03 medical and health sciences, symbols.namesake, Neonatal Screening, 0302 clinical medicine, Agammaglobulinemia, Polysaccharides, immune system diseases, hemic and lymphatic diseases, Agammaglobulinaemia Tyrosine Kinase, Humans, Bruton's tyrosine kinase, Medicine, Child, Gene, Sanger sequencing, Newborn screening, biology, business.industry, Infant, Newborn, General Medicine, Phenotype, Staining, Vaccination, 030104 developmental biology, Child, Preschool, Mutation, biology.protein, symbols, Phosphorylation, Symptom Assessment, business, Biomarkers, Follow-Up Studies, 030215 immunology |
| الوصف: | Hypomorphic mutations in the gene encoding Bruton tyrosine kinase (BTK) may result in milder phenotypes and delayed diagnosis of B-cell related immunodeficiencies due to residual BTK function. Newborn screening for kappa-deleting-recombination-excision circles (KRECs) reliably identifies classical X-linked agammaglobulinaemia (XLA) patients with profound B-cell lymphopenia at birth but has not been evaluated in patients with residual BTK function. We aimed to evaluate clinical findings, BTK function and KREC copy numbers in three patients with BTK mutations presenting with impaired polysaccharide responsiveness without agammaglobulinaemia. One patient had an invasive pneumococcal infection at the age of 4 years. All three patients (two brothers) had visible tonsils, normal to slightly decreased immunoglobulin G levels, undetectable pneumococcal antibodies despite pneumococcal conjugate vaccinations, no antibody response after a diagnostic polysaccharide vaccination as well as profound B-cell lymphopenia with residual B-cell differentiation. BTK mutations were identified by Sanger sequencing. BTK staining and phosphorylation assays were performed on peripheral B cells. KREC copy numbers were determined from dried blood spots obtained within the first week of life as well as once at the age of 8, 6 and 3 years, respectively. BTK staining showed residual protein expression. Also, residual BTK activity could be demonstrated. KREC copy numbers from dried blood spots were above the threshold set for detection of patients with profound B-cell lymphopenia. Male patients with impaired polysaccharide responsiveness should be evaluated for B-cell lymphopenia followed by BTK analyses irrespective of immunoglobulin levels or tonsil size. |
| تدمد: | 1365-3083 0300-9475 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::88a2c720f2b5c9549196bb3dab1be160Test https://doi.org/10.1111/sji.12811Test |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....88a2c720f2b5c9549196bb3dab1be160 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 13653083 03009475 |
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