Linfócitos T auxiliares foliculares e subpopulações de linfócitos B em pacientes com ataxia-telangiectasia
Data
2023-05-04
Autores
Nobre, Fernanda Aimée 
Orientadores
Pinto, Maria Isabel de Moraes
Tipo
Tese de doutorado
Título da Revista
ISSN da Revista
Título de Volume
Resumo
Objetivo: Avaliar as células T auxiliares foliculares e as subpopulações de células B em pacientes com ataxia-telangiectasia. Métodos: Foram selecionados 11 pacientes com a forma clássica da ataxia-telangiectasia e 10 indivíduos saudáveis pareados pela idade como grupo controle. As células T auxiliares foliculares circulantes e suas subpopulações, assim como a expressão das moléculas coestimuladora induzível de linfócitos T e proteína de morte celular programada 1 foram analisadas por citomeria de fluxo. Nove subpopulações de linfócitos B também foram analisadas por citometria de fluxo. Os dados obtidos nos pacientes com ataxia-telangiectasia foram comparados aos do grupo controle. Resultados: O número absoluto das células T auxiliares foliculares circulantes estava significativamente reduzido nos pacientes com ataxia-telangiectasia (pacientes = 15,48 versus controles = 56,47, p = 0,0009). Já a proporção dessas células foi similar entre pacientes e controles. Em relação às subpopulações das células T auxiliares foliculares circulantes, foi observada uma proporção reduzida de células T auxiliares foliculares circulantes tipo 17 na ataxia-telangiectasia, o que configurou um achado relevante (pacientes = 1,37 versus controles = 10,43, p = 0,0092). Já as células T auxiliares foliculares circulantes tipo 1 e as células T auxiliares foliculares circulantes tipo 2 mostraram uma proporção semelhante entre os dois grupos estudados. Não foram observadas diferenças entre pacientes e controles em relação à expressão das moléculas coestimuladora induzível de linfócitos T e proteína de morte celular programada 1. Quanto aos linfócitos B, a proporção de células B transicionais (pacientes = 0,057 versus controles = 1,07, p = 0,0054) e de células B naive maduras (pacientes = 24,3 versus controles = 57,7, p = 0,006) estavam diminuídas nos pacientes com ataxia-telangiectasia. Observou-se também um aumento da subpopulação de células B CD21lowCD38low nesses pacientes (pacientes = 36,6 versus controles = 15,55, p = 0,0004). Sobre as células B de memória, os pacientes com ataxia-telangiectasia apresentaram uma proporção reduzida de células B de memória com troca de isotipo (pacientes = 53,2 versus controles = 69,7 p = 0,0039) e aumentada de células B IgM-only (pacientes = 15,5 versus controles = 3,20, p = 0,0001), sem diferença observada nas demais subpopulações, que incluíram células B de memória sem troca de isotipo, células de memória IgG típica e atípica e plasmablastos, quando comparadas às do grupo controle. Conclusões: As células T auxiliares foliculares não haviam sido estudadas na ataxia telangiectasia. A diminuição do número absoluto das células T auxiliares foliculares circulantes e da proporção das células T auxiliares foliculares circulantes tipo 17 corroboram a hipótese de um comprometimento da imunidade humoral dependente de linfócitos T e de uma disfunção da resposta de centro germinativo como mecanismo relacionado à imunodeficiência na ataxia-telangiectasia. A redução das células B de memória com troca de isotipo e o aumento das células B IgM-only também reforçam tal hipótese.
Objective: This study aimed to assess follicular helper T cells and B cell subsets in patients with ataxia-telangiectasia. Methods: Eleven patients with the classic form of ataxia-telangiectasia and 10 age-matched healthy individuals were selected. Circulating follicular helper T cells and their subpopulations, as well as the expression of inducible T-cell co-stimulator and programmed cell death protein 1 molecules were analyzed by flow cytometry. Nine subsets of B lymphocytes were also analyzed by flow cytometry. Data obtained from patients with ataxia-telangiectasia were compared to those from the control group. Results: The absolute number of circulating follicular helper T cells was significantly reduced in patients with ataxia-telangiectasia (patients = 15.48 versus controls = 56.47, p = 0.0009). The proportion of these cells was similar between patients and controls. Regarding the subpopulations of circulating follicular helper T cells, a reduced proportion of circulating follicular helper T cells type 17 was observed in ataxia-telangiectasia, which constituted a relevant finding (patients = 1.37 versus controls = 10.43, p = 0.0092). Circulating follicular helper T cells type 1 and circulating follicular helper T cells type 2 showed a similar proportion between the two studied groups. Furthermore, no differences were observed between patients and controls regarding the expression of inducible T-cell co-stimulator and programmed cell death protein 1 molecules. With regard to B lymphocytes, the proportion of transitional B cells (patients = 0.057 versus controls = 1.07, p = 0.0054) and naive B cells (patients = 24.3 versus controls = 57.7, p = 0.006) were reduced in patients with ataxia-telangiectasia. An increase in the CD21lowCD38low B-cells was also observed in these patients (patients = 36.6 versus controls = 15.55, p = 0.0004). Regarding memory B cells, patients with ataxia-telangiectasia had a reduced proportion of switched memory B cells (patients = 53.2 versus controls = 69.7 p = 0.0039) and an increased proportion of IgM-only B cells (patients = 15.5 versus controls = 3.20, p = 0.0001). No differences were observed when comparing the ataxia-telangiectasia and control groups in the other subpopulations, which included unswitched memory B cells, typical memory IgG B cells, atypical memory IgG B cells and plasmablasts. Conclusions: Follicular helper T cells have not been studied in ataxia-telangiectasia. The decrease in the absolute number of circulating follicular helper T cells and in the proportion of circulating follicular helper T cells type 17 support the hypothesis of an impairment of T-dependent humoral immunity and of a dysfunction of the germinal center response as a mechanism related to immunodeficiency in ataxia-telangiectasia. The reduction in switched memory B cells and the increase in IgM-only B cells also reinforce this hypothesis.
Objective: This study aimed to assess follicular helper T cells and B cell subsets in patients with ataxia-telangiectasia. Methods: Eleven patients with the classic form of ataxia-telangiectasia and 10 age-matched healthy individuals were selected. Circulating follicular helper T cells and their subpopulations, as well as the expression of inducible T-cell co-stimulator and programmed cell death protein 1 molecules were analyzed by flow cytometry. Nine subsets of B lymphocytes were also analyzed by flow cytometry. Data obtained from patients with ataxia-telangiectasia were compared to those from the control group. Results: The absolute number of circulating follicular helper T cells was significantly reduced in patients with ataxia-telangiectasia (patients = 15.48 versus controls = 56.47, p = 0.0009). The proportion of these cells was similar between patients and controls. Regarding the subpopulations of circulating follicular helper T cells, a reduced proportion of circulating follicular helper T cells type 17 was observed in ataxia-telangiectasia, which constituted a relevant finding (patients = 1.37 versus controls = 10.43, p = 0.0092). Circulating follicular helper T cells type 1 and circulating follicular helper T cells type 2 showed a similar proportion between the two studied groups. Furthermore, no differences were observed between patients and controls regarding the expression of inducible T-cell co-stimulator and programmed cell death protein 1 molecules. With regard to B lymphocytes, the proportion of transitional B cells (patients = 0.057 versus controls = 1.07, p = 0.0054) and naive B cells (patients = 24.3 versus controls = 57.7, p = 0.006) were reduced in patients with ataxia-telangiectasia. An increase in the CD21lowCD38low B-cells was also observed in these patients (patients = 36.6 versus controls = 15.55, p = 0.0004). Regarding memory B cells, patients with ataxia-telangiectasia had a reduced proportion of switched memory B cells (patients = 53.2 versus controls = 69.7 p = 0.0039) and an increased proportion of IgM-only B cells (patients = 15.5 versus controls = 3.20, p = 0.0001). No differences were observed when comparing the ataxia-telangiectasia and control groups in the other subpopulations, which included unswitched memory B cells, typical memory IgG B cells, atypical memory IgG B cells and plasmablasts. Conclusions: Follicular helper T cells have not been studied in ataxia-telangiectasia. The decrease in the absolute number of circulating follicular helper T cells and in the proportion of circulating follicular helper T cells type 17 support the hypothesis of an impairment of T-dependent humoral immunity and of a dysfunction of the germinal center response as a mechanism related to immunodeficiency in ataxia-telangiectasia. The reduction in switched memory B cells and the increase in IgM-only B cells also reinforce this hypothesis.