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Functional evaluation of B cell subsets in children with hypogammaglobulinemia

Abstract

Hypogammaglobulinemia is the reduction of serum immunoglobulin levels due to primary or secondary causes. Common Variable Immunodeficiency (CVID) is a primary hypogammaglobulinemia clinically defined by the presence of recurrent infections after 2 years of age, a reduction of IgG levels and at least one other Ig isotype. The CVID patients also present a failure to generate a specific antibody response after vaccination or natural infection. In CVID, other known genetic or acquired causes of hypogammaglobulinemia have been excluded. Several studies have shown alterations in B lymphocytes in CVID adult patients, but there is insufficient data on these cells in children.Our hypothesis is that children and adults with CVID present separate distinct features, especially regarding B cells subsets. The objective of this project is to study the B lymphocyte subsets in children with hypogammaglobulinemia and to compare these with healthy controls matched by gender and age (10 children). The patients with CVID diagnosis (10 children and 10 adults) will be selected from the Division of Allergy, Clinical Immunology and Rheumatology -UNIFESP. All patients are being treated with regular intravenous immunoglobulin (IVIG). Clinical data will be collected by questionnaire based on the medical reports. For each subject, blood samples will be colleted immediately before IVIG infusion. We will study the number of TCD3, CD4, CD8, B cells (CD19) and Natural Killer cells (CD16 / CD56) by flow citometry. In order to study B cells subsets in depth we will use markers for:: 1- maturation: CD10, CD21, CD27, IgM, IgD and CD38; 2- activation: CD38, HLA-DR e CCR7; 3- regulatory B cells : CD24 and CD38. T cell function will be studied by interferon-gamma production after stimulation with tetanus antigen and the number of regulatory T cells will be quantified using CD25 and FOXP3 markers.The results of this study will allow a better understanding of B lymphocytes in children with hypogammaglobulinemia. Considering the heterogeneity of CVID, we intend to show that lymphocytes in children with this disease have distinct functional and phenotypic characteristics when compared with those of adult patients with CVID. A greater insight into B cells in this group of patients will help us in their management. (AU)

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Scientific publications
(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)
DE MELO, KARINA MESCOUTO; DE MORAES-PINTO, MARIA ISABEL; ANDRADE, LUIS E. C.; SALOMAO, REINALDO; BRUNIALTI, MILENA K. C.; FERREIRA, VANESSA S.; COSTA-CARVALHO, BEATRIZ T. Hypogammaglobulinemia in children: a warning sign to look deeply?. APMIS, v. 125, n. 10, p. 902-909, OCT 2017. Web of Science Citations: 1.

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