Reduced numbers of switched memory B cells with high terminal differentiation potential in Down syndrome |
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| Authors: | Rita Carsetti Diletta Valentini Valentina Marcellini Marco Scarsella Emiliano Marasco Ferruccio Giustini Andrea Bartuli Alberto Villani Alberto G. Ugazio |
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| Affiliation: | 1. Immunology Unit, Immunology and Pharmacotherapy Area, Bambino Gesù Children's Hospital, IRCCS, Rome, Italy;2. Diagnostic Immunology Unit, Department of Laboratories, Bambino Gesù Children's Hospital, IRCCS, Rome, Italy;3. Pediatric and Infectious Disease Unit, Bambino Gesù Children's Hospital, IRCCS, Rome, Italy;4. Department of Laboratories, Bambino Gesù Children's Hospital, IRCCS, Rome, Italy;5. Rare Disease and Medical Genetics Unit, Bambino Gesù Children's Hospital, IRCCS, Rome, Italy;6. Department of Pediatrics, Bambino Gesù Children's Hospital, IRCCS, Rome, Italy |
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| Abstract: | Children with Down syndrome (DS) have increased susceptibility to infections and a high frequency of leukemia and autoimmune disorders, suggesting that immunodeficiency and immune dysfunction are integral parts of the syndrome. A reduction in B‐cell numbers has been reported, associated with moderate immunodeficiency and normal immunoglobulin levels. Here, we compared B‐cell populations of 19 children with DS with those in healthy age‐matched controls. We found that all steps of peripheral B‐cell development are altered in DS, with a more severe defect during the later stages of B‐cell development. Transitional and mature‐naïve B‐cell numbers are reduced by 50% whereas switched memory B cells represent 10–15% of the numbers in age‐matched controls. Serum IgM levels were slightly reduced, but all other immunoglobulin isotypes were in the normal range. The frequency of switched memory B cells specific for vaccine antigens was significantly lower in affected children than in their equivalently vaccinated siblings. In vitro switched memory B cells of patients with DS have an increased ability to differentiate into antibody‐forming cells in response to TLR9 signals. Tailored vaccination schedules increasing the number of switched memory B cells may improve protection and reduce the risk of death from infection in DS. |
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| Keywords: | B cells Down syndrome IgM memory Switched memory TLR9 Vaccine |
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