Reduced numbers of switched memory B cells with high terminal differentiation potential in Down syndrome

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.

Caracterização dos pacientes e procedimentos executados no serviço de atendimento a pacientes com necessidades especiais da Faculdade de Odontologia de Araraquara – UNESP

“…Aproximadamente 10% dos pacientes atendidos apresentavam Síndrome de Down, a qual está relacionada com limitações no desenvolvimento físico e mental, e com deficiência imunológica 16,17 . Esta última, associada à má higiene bucal que esses indivíduos Indivíduos com alterações neurológicas geralmente apresentam redução do fluxo e do pH salivares, em virtude da utilização sistemática de medicamentos, como os anticonvulsivantes, antipsicóticos, ansiolíticos, antiepilépticos e antidepressivos 19 .…”

What people with Down Syndrome can teach us about cardiopulmonary disease

“…Following vaccination to influenza A or polysaccharide pneumococcus, antibody responses are active in persons with Down syndrome, yet antibody titres are lower [166,169,177,178]. One possible contribution to increased prevalence and severity of pulmonary infection in Down syndrome could be reduced numbers of subsets of B-cells, such as switched memory B-cells [179,180]. Deficit of such cells in Down syndrome could result in suboptimal protection from, and response to, infectious agents.…”

Effects of Pidotimod on recurrent respiratory infections in children with Down syndrome: a retrospective Italian study

“…Recently, other authors and we reported that DS is associated with a primary defect of the B-cell compartment, characterized by a reduced number of all B-cells in the peripheral blood and especially of memory B cells. IgM memory B cells representing the first-line defense against infection [10] are 1/3 of normal, whereas highly specific switched memory B cells are 7-10 fold less than expected [11,12]. We have also shown that children with DS respond poorly to primary immunization and their protection may require tailored vaccination protocols [13].…”