A carregar...
Publicação
Revisitando a infeção CMV na gravidez: de um momento imunotolerate ao momento do parto
| Nome: | Descrição: | Tamanho: | Formato: | |
|---|---|---|---|---|
| 4.89 MB | Adobe PDF |
Resumo(s)
Resumo: A gravidez é um período desafiante que compreende algumas oscilações ao nível do sistema imunitário. Vários fatores podem ameaçar a normal dinâmica imunitária da gravidez, comprometendo o bem-estar da mãe e do feto, como acontece com a infeção por Citomegalovírus (CMV). Esta infeção apresenta elevada prevalência a nível global, sendo o seu efeito a longo prazo no sistema imunitário ainda pouco caracterizado, principalmente no contexto da gravidez. O Torque Teno Vírus (TTV) é um agente ubíquo e potencialmente não patogénico, apontado como promissor indicador de imunossupressão em doentes transplantados, nos quais a viremia do TTV tem sido proposta como marcador preditivo de reativação da infeção por CMV. Esta aplicação carece de evidências consistentes, tendo sido pouco explorada ainda no período gestacional. O presente estudo teve como objetivos a caracterização de subpopulações de linfócitos B e T em mulheres grávidas saudáveis, para avaliação posterior do impacto do CMV nas suas dinâmicas ao longo da gravidez, e ainda o potencial da carga viral de TTV enquanto indicador de imunossupressão na gestação. Foram recrutadas 55 mulheres grávidas e 15 mulheres não grávidas saudáveis, e realizadas colheitas de sangue periférico em cada trimestre de gravidez nas mulheres grávidas e no recrutamento nas não grávidas. O perfil imunitário foi analisado por citometria de fluxo. A pesquisa de anticorpos específicos contra CMV utilizou ensaios de quimioluminescência e as cargas virais de CMV e de TTV foram avaliadas por qPCR em tempo real. O perfil imunitário das mulheres grávidas revelou diminuição de linfócitos B totais e linfócitos B de transição, tanto ao longo da gravidez como em relação a mulheres não grávidas. Por sua vez, o compartimento T revelou na generalidade valores absolutos mais baixos durante a gravidez, com um aumento progressivo até ao 3.º trimestre nos valores percentuais de células T totais e nas populações de linfócitos T CD8+ e T DN ativados. Considerando o impacto do CMV no perfil imune da gravidez, verificaram-se níveis mais elevados de ativação no compartimento T circulante em grávidas seropositivas, à imagem de estudos noutras coortes. Porém, relatamos aqui pela primeira vez alterações ao nível de linfócitos B de memória e plasmablastos, mais elevados, sobretudo no 2.º trimestre, em grávidas com infeção prévia por CMV. Este é ainda o primeiro estudo a avaliar populações de células T foliculares em função do background viral, mostrando que grávidas seropositivas para CMV apresentam contagens mais elevadas destas células no primeiro trimestre, em relação a mulheres seronegativas no mesmo período. Considerando as subpopulações celulares em função dos dados de carga viral de TTV, verificaram-se sobretudo níveis mais elevados de células T foliculares ativadas na gravidez em mulheres sem carga viral. Este estudo pioneiro permitiu rever o conhecimento atual do perfil imune da gravidez à luz do impacto da infeção por CMV, que aqui surge como eventual trigger de ativação das respostas. Os seus resultados abrem caminho para abordagens em coortes de maior dimensão que validem estas observações, e as considerem também à luz de outras ocorrências, como a primoinfeção ou a reativação, relevantes também na gravidez.
Abstract: Pregnancy is a challenging period which imposes some alterations to the immune system. There are many factors that can disturb the normal immune dynamics of pregnancy, possibly jeopardizing mother and fetus well-being, such as the Cytomegalovirus (CMV) infection, which presents a high global prevalence, whereas its long-term impact on the immune system is still not completely characterized, especially in the context of pregnancy. Torque Teno Virus (TTV) is a ubiquitous and potentially non-pathogenic agent, suggested as a promising immunosuppression marker in transplanted patients, where TTV viral load has been considered a marker for CMV reactivation. This interplay lacks more consistent evidence and has been poorly explored also considering the immune dynamics of gestation. The present study aimed to characterize various B and T lymphocyte subpopulations on healthy pregnant women, as well as assessing the impact of CMV on the immune dynamics of pregnancy and the potential of TTV viral load as immunosuppression indicator in gestation. In this context, 55 healthy pregnant women and 15 healthy non-pregnant women were recruited. Blood samples were collected in each trimester of pregnancy for the pregnant women and at recruitment for non-pregnant participants. Immune profiles were analysed using flow cytometry. Additionally, anti-CMV antibodies were quantified by chemiluminescence and viral loads of CMV and TTV were amplified by real time qPCR. The immune profile of pregnant women revealed decreased total B cells and transitional B cells, both along pregnancy and also compared to non-pregnant women. The T cell compartment showed in general lower absolute values during pregnancy, with a progressive increase until the 3rd trimester in the percentage values of total T cells and in the populations of activated CD8+ T lymphocytes and activated DN T lymphocytes. Considering the impact of CMV on the immunological profile of pregnancy, higher levels of activation in the circulating T compartment were observed in seropositive pregnant women, in line with studies in other cohorts. However, here we report for the first time changes in the levels of memory B lymphocytes and plasmablasts, which were higher, especially in the 2nd trimester, in pregnant women with previous CMV infection. This is also the first study evaluating follicular T cells according to the viral background, showing that CMV-seropositive pregnant women have higher absolute counts of these cells in the first trimester, compared to seronegative women in the same period. Considering the cell subpopulations according to the TTV viral load data, we found particularly higher levels of activated follicular T cells during pregnancy in women with no viral load. This pioneer study allowed us to review the current knowledge on the immune profile of pregnancy in light of the impact of CMV infection, which appears as a possible trigger for the activation of immune responses. Its results pave the way for approaches in larger cohorts that may validate our observations, but also consider occurrences, such as primary infection or reactivation, both very relevant for the success of pregnancy.
Abstract: Pregnancy is a challenging period which imposes some alterations to the immune system. There are many factors that can disturb the normal immune dynamics of pregnancy, possibly jeopardizing mother and fetus well-being, such as the Cytomegalovirus (CMV) infection, which presents a high global prevalence, whereas its long-term impact on the immune system is still not completely characterized, especially in the context of pregnancy. Torque Teno Virus (TTV) is a ubiquitous and potentially non-pathogenic agent, suggested as a promising immunosuppression marker in transplanted patients, where TTV viral load has been considered a marker for CMV reactivation. This interplay lacks more consistent evidence and has been poorly explored also considering the immune dynamics of gestation. The present study aimed to characterize various B and T lymphocyte subpopulations on healthy pregnant women, as well as assessing the impact of CMV on the immune dynamics of pregnancy and the potential of TTV viral load as immunosuppression indicator in gestation. In this context, 55 healthy pregnant women and 15 healthy non-pregnant women were recruited. Blood samples were collected in each trimester of pregnancy for the pregnant women and at recruitment for non-pregnant participants. Immune profiles were analysed using flow cytometry. Additionally, anti-CMV antibodies were quantified by chemiluminescence and viral loads of CMV and TTV were amplified by real time qPCR. The immune profile of pregnant women revealed decreased total B cells and transitional B cells, both along pregnancy and also compared to non-pregnant women. The T cell compartment showed in general lower absolute values during pregnancy, with a progressive increase until the 3rd trimester in the percentage values of total T cells and in the populations of activated CD8+ T lymphocytes and activated DN T lymphocytes. Considering the impact of CMV on the immunological profile of pregnancy, higher levels of activation in the circulating T compartment were observed in seropositive pregnant women, in line with studies in other cohorts. However, here we report for the first time changes in the levels of memory B lymphocytes and plasmablasts, which were higher, especially in the 2nd trimester, in pregnant women with previous CMV infection. This is also the first study evaluating follicular T cells according to the viral background, showing that CMV-seropositive pregnant women have higher absolute counts of these cells in the first trimester, compared to seronegative women in the same period. Considering the cell subpopulations according to the TTV viral load data, we found particularly higher levels of activated follicular T cells during pregnancy in women with no viral load. This pioneer study allowed us to review the current knowledge on the immune profile of pregnancy in light of the impact of CMV infection, which appears as a possible trigger for the activation of immune responses. Its results pave the way for approaches in larger cohorts that may validate our observations, but also consider occurrences, such as primary infection or reactivation, both very relevant for the success of pregnancy.
Descrição
Palavras-chave
CMV Pregnancy TTV Immune Profile