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Inicio Allergologia et Immunopathologia B-cell subsets imbalance and reduced expression of CD40 in ataxia-telangiectasia...
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Vol. 46. Issue 5.
Pages 438-446 (September - October 2018)
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Vol. 46. Issue 5.
Pages 438-446 (September - October 2018)
Original Article
DOI: 10.1016/j.aller.2017.09.031
B-cell subsets imbalance and reduced expression of CD40 in ataxia-telangiectasia patients
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C.T.M. Pereiraa,1, D.C. Bichuetti-Silvaa,1, N.V.F. da Motab, R. Salomãob, M.K.C. Brunialtib, B.T. Costa-Carvalhoa,
Corresponding author
beacarvalho@terra.com.br

Corresponding author.
a Department of Pediatrics, Federal University of Sao Paulo Medical School, 598, Botucatu Street, Vila Clementino, São Paulo, SP 04023-062, Brazil
b Division of Infectious Diseases, Federal University of Sao Paulo Medical School, 669, Pedro de Toledo Street, Vila Clementino, São Paulo, SP 04039-032, Brazil
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Table 1. Ataxia-telangiectasia patients’ characteristics.
Table 2. Total counts of lymphocytes and subpopulations in AT patients (n=18) and controls (n=15).
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Abstract
Background

Ataxia-telangiectasia (AT) is a well-known primary immunodeficiency with recurrent sinopulmonary infections and variable abnormalities in both the humoral and cellular immune system. Dysfunctions in immunoglobulin production, reduced number of B cells, and B-cell receptor excision circles copies have been reported. We aimed to understand the immunological mechanisms involving the humoral compartment in AT patients by analysing peripheral blood B cells subsets, B-T lymphocyte cooperation through the expression of CD40 and CD40 ligand (CD40L), and cytokines involved in class-switch recombination production.

Methods

We compared the proportion of B-cell subsets, the expression of CD40/CD40L, and the plasma levels of IL-6 and IFN-γ of 18 AT patients and 15 healthy age-sex-matched controls using flow cytometry.

Results

We found that some steps in peripheral B cell development were altered in AT with a pronounced reduction of cell-surface CD40 expression. The proportions of transitional and naïve-mature B cells were reduced, whereas CD21-low, natural effector memory, IgM-only memory, and IgG atypical memory B cells were present in a higher proportion.

Conclusions

These findings revealed a disturbed B-cell homeostasis with unconventional maturation of B lymphocyte memory cells, which can explain the consequent impairment of humoral immunity.

Keywords:
Ataxia-telangiectasia
B cells
CD40
CD40L
IgM memory B cells
Switched memory B cells
CD21low

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