“Translocação microbiana, inflamação e desequilíbrio do sistema redox na gestação e pós parto de mulheres infectadas pelo HIV”
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2020-02-19
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Manfio, Vanessa Martinez
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Universidade Estadual Paulista (Unesp)
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Introdução: O estado redox, translocação microbiana e ativação imune são processos pouco estudados em gestantes infectadas pelo HIV. Estes temas têm extrema relevância, afinal, podem comprometer a homeostasia de processos fisiológicos indispensáveis para o desenvolvimento intrauterino e evolução gestacional, ou contribuir para aquisição de comorbidades associadas ou não à aids nestas mulheres. Objetivo: Avaliar a translocação microbiana, ativação imune e estado redox durante a gestação e pós-parto de mulheres infectadas pelo HIV. Casuística e metodologia: As 39 mulheres incluídas pertenceram aos seguintes grupos: 13 gestantes HIV+, 10 gestantes HIV-, 10 mulheres não grávidas HIV- e, seis mulheres não grávidas HIV+. Foram coletados dados clínicos e sociodemográficos pela análise de prontuários e entrevistas. O sangue foi coletado em um único momento, para as não gestantes, e em três momentos para as gestantes, sendo: primeiro ou segundo trimestres (M0), pré-parto (M1) e pós-parto (M2). Foram analisados os seguintes parâmetros de estresse oxidativo e translocação microbiana, respectivamente: atividade da peróxido dismutase (SOD), catalase (CAT), carbonilação proteica, proteína de ligação de ácidos graxos intestinais (iFABP), lipopolissacarídio (LPS), cluster de diferenciação 14 solúvel (sCD14) e anticorpos do core da endotoxina (EndoCAb, IgG, IgA e IgM). A análise estatística foi baseada em dois modelos, um fatorial, considerando dois fatores de classificação (gestação e infecção), e um longitudinal para os grupos, combinando gestação e infecção. Os resultados foram analisados por ANOVA seguido de Tukey e distribuição Gamma seguido de Wald, considerando nível de significância de 5%. Resultados: A média de idade geral foi de 31,5 (±7,18) anos. Para as gestantes infectadas, as contagens de linfócitos T CD4+ apresentaram-se em sua grande maioria, acima de 500 células/mm3, enquanto que 54,0% dessas mulheres possuíam CV acima do limite de detecção no momento da inclusão no estudo. Na avaliação do estado redox pelo modelo longitudinal, as gestantes (HIV+ e HIV-) não apresentaram alteração na atividade de SOD, entretanto, a atividade de CAT foi aumentada no pós-parto das infectadas (p=0,03) e no pré- e pós-parto das não infectadas (p=0,0004 e p=0,001). A elevação da carbonilação ocorreu apenas no pré-parto das gestantes não infectadas (p=0,01). Pelo modelo fatorial, maiores atividades de SOD e CAT foram observadas nas HIV+, tanto nas mulheres que estavam nos meses iniciais da gestação (p=0,04 e p=0,02, respectivamente) quanto nas não gestantes (p=0,007 e p=0,008); apesar disso, o fator gestação nestas mulheres infectadas parece diminuir consideravelmente os níveis de CAT (p=0,004). Neste mesmo modelo, a carbonilação no pré-parto foi mais evidente nas grávidas HIV- (p=0,01), do que nas HIV+, sendo que o inverso ocorre quando o fator gestação é excluído (p=0,01). Em relação à translocação microbiana, pelos modelos longitudinal e fatorial, níveis de iFABP foram maiores nas gestantes infectadas [(M0 p=0,001; M1 p=0,009; M2 p<0,0001 longitudinal) e (M0 p=0,03, M1 p=0,01 e M2 p=0,007 fatorial)]. As dosagens de LPS foram maiores em gestantes HIV+, do que nas gestantes HIV- (M0 p=0,0005, M1 p=0,0008 e M2 p=0,0001), o que foi ainda mais expressivo no pós-parto, considerando ambos os modelos [(M2 p=0,0007 longitudinal) e (M2 p=0,004 fatorial)]. Quanto ao sCD14, o modelo longitudinal mostrou maiores dosagens no início da gestação (M0 p=0,02), enquanto o modelo fatorial não mostrou diferença entre as HIV- mas, considerando só as HIV+, esses níveis foram maiores em não gestantes (M0 p<0,0001. M1 p<0,0001 e M2 p<0,0001). Para o EndoCAB das gestantes, as HIV+ apresentaram maiores IgA [(p=0,001 longitudinal) e (p=0,02 fatorial)] e IgM [(p=0,02 longitudinal) e (p=0,03 fatorial)] nos primeiros trimestres gestacionais. Enquanto as HIV- não gestantes apresentaram maiores níveis de IgA (p=0,02 fatorial), as HIV+ apresentaram os valores mais altos de IgM no pós-parto, em relação às não infectadas (p=0,05). Conclusão: Maior estresse oxidativo pode ocorrer em gestantes infectadas pelo HIV, porém, o vírus não é o único responsável por este processo, no qual parece haver envolvimento de outros mecanismos relacionados à gestação. A infecção promoveu maior translocação microbiana e ativação imune em infectadas pelo HIV, e a gestação por sua vez, diminuiu este último nestas mulheres, como visto pelo LPS, sCD14, IgM e IgA.
Introduction: Redox state, microbial translocation and immune activation are poorly studied processes in HIV-infected pregnant women. These themes have extreme relevance, after all, may compromise the homeostasis of physiological processes indispensable for intrauterine development and gestational evolution, or contribute to the acquisition of comorbidities associated or not with AIDS in these women. Objective: To evaluate microbial translocation, immune activation and redox status during pregnancy and postpartum of HIV-infected women. Methodology: The 39 women included belonged to the following groups: 13 HIV+ pregnant women, 10 HIV-pregnant women, 10 nonpregnant HIV-and, six non-pregnant HIV+ women. Clinical and sociodemographic data were collected from the analysis of medical records and interviews. Blood was collected in a single moment for nonpregnant women, and in three moments for pregnant women, being: first or second trimesters (M0), prepartum (M1) and postpartum (M2). The following parameters of oxidative stress and microbial translocation were analyzed, respectively: peroxide dismutase activity (SOD), catalase (CAT), protein carbonylation, intestinal fatty acid binding protein (iFABP), lipopolysaccharide (LPS), soluble differentiation cluster 14 (sCD14) and endotoxin core antibodies (EndoCAb, IgG, IgA and IgM). The statistical analysis was based on two models, a factorial, considering two classification factors (pregnancy and infection), and one longitudinal for the groups, combining pregnancy and infection. The results were analyzed by ANOVA followed by Tukey and Gamma distribution followed by Wald, considering significance level of 5%. Results: The mean general age was 31.5 (±7.18) years. For infected pregnant women, CD4+ T lymphocyte counts were mostly above 500 cells/mm3, while 54.0% of these women had CV above the detection limit at the time of inclusion in the study. In the evaluation of the redox state by the longitudinal model, pregnant women (HIV+ and HIV-) did not present alterations in SOD activity, however, CAT activity was increased in the postpartum of the infected (p=0.03) and in the pre- and postpartum of the non-infected (p=0.0004 and p=0.001). The increase in carbonylation occurred only in the prepartum of non-infected pregnant women (p=0.01). By the factorial model, higher activities of SOD and CAT were observed in HIV+, both in women who were in the initial months of pregnancy (p=0.04 and p=0.02, respectively) and in non-pregnant women (p=0.007 and p=0.008); despite this, the pregnancy factor in these infected women seems to considerably decrease CAT levels (p=0.004). In this same model, carbonylation in prepartum was more evident in pregnant HIV- (p=0.01), than in HIV+, and the reverse occurs when the pregnancy factor is excluded (p=0.01). Regarding microbial translocation, longitudinal and factorial models, iFABP levels were higher in infected pregnant women [(M0 p=0.001; M1 p=0.009; M2 p<0.0001 longitudinal) and (M0 p=0.03, M1 p=0.01 and M2 p=0.007 factorial)]. LPS dosages were higher in HIV+ pregnant women, than in HIV-pregnant women ( M0 p=0.0005, M1 p=0.0008 and M2 p=0.0001), which was even more expressive in the postpartum period, considering both models [(M2 p=0.0007 longitudinal) and (M2 p=0.004 factorial)]. Regarding sCD14, the longitudinal model showed higher dosages at the beginning of pregnancy (M0 p=0.02), while the factorial model showed no difference between HIVbut, considering only HIV+, these levels were higher in non-pregnant women (M0 p<0.0001. M1 p<0.0001 and M2 p<0.0001). For the EndoCAb of pregnant women, HIV+ presented higher IgA [(p=0.001 longitudinal) and (p=0.02 factorial)] and IgM [(p=0.02 longitudinal) and (p=0.03 factorial)] in the first gestational trimesters. While hiv-non-pregnant women had higher levels of IgA (p=0.02 factorial), HIV+ presented the highest values of IgM in the postpartum period, in relation to noninfected patients (p=0.05). Conclusion: Increased oxidative stress can occur in HIV-infected pregnant women, however, the virus is not solely responsible for this process, in which there seems to be involvement of other mechanisms related to pregnancy. The infection promoted greater microbial translocation and immune activation in HIV-infected, and pregnancy in turn decreased the latter in these women, as seen by LPS, sCD14, IgM and IgA.
Introduction: Redox state, microbial translocation and immune activation are poorly studied processes in HIV-infected pregnant women. These themes have extreme relevance, after all, may compromise the homeostasis of physiological processes indispensable for intrauterine development and gestational evolution, or contribute to the acquisition of comorbidities associated or not with AIDS in these women. Objective: To evaluate microbial translocation, immune activation and redox status during pregnancy and postpartum of HIV-infected women. Methodology: The 39 women included belonged to the following groups: 13 HIV+ pregnant women, 10 HIV-pregnant women, 10 nonpregnant HIV-and, six non-pregnant HIV+ women. Clinical and sociodemographic data were collected from the analysis of medical records and interviews. Blood was collected in a single moment for nonpregnant women, and in three moments for pregnant women, being: first or second trimesters (M0), prepartum (M1) and postpartum (M2). The following parameters of oxidative stress and microbial translocation were analyzed, respectively: peroxide dismutase activity (SOD), catalase (CAT), protein carbonylation, intestinal fatty acid binding protein (iFABP), lipopolysaccharide (LPS), soluble differentiation cluster 14 (sCD14) and endotoxin core antibodies (EndoCAb, IgG, IgA and IgM). The statistical analysis was based on two models, a factorial, considering two classification factors (pregnancy and infection), and one longitudinal for the groups, combining pregnancy and infection. The results were analyzed by ANOVA followed by Tukey and Gamma distribution followed by Wald, considering significance level of 5%. Results: The mean general age was 31.5 (±7.18) years. For infected pregnant women, CD4+ T lymphocyte counts were mostly above 500 cells/mm3, while 54.0% of these women had CV above the detection limit at the time of inclusion in the study. In the evaluation of the redox state by the longitudinal model, pregnant women (HIV+ and HIV-) did not present alterations in SOD activity, however, CAT activity was increased in the postpartum of the infected (p=0.03) and in the pre- and postpartum of the non-infected (p=0.0004 and p=0.001). The increase in carbonylation occurred only in the prepartum of non-infected pregnant women (p=0.01). By the factorial model, higher activities of SOD and CAT were observed in HIV+, both in women who were in the initial months of pregnancy (p=0.04 and p=0.02, respectively) and in non-pregnant women (p=0.007 and p=0.008); despite this, the pregnancy factor in these infected women seems to considerably decrease CAT levels (p=0.004). In this same model, carbonylation in prepartum was more evident in pregnant HIV- (p=0.01), than in HIV+, and the reverse occurs when the pregnancy factor is excluded (p=0.01). Regarding microbial translocation, longitudinal and factorial models, iFABP levels were higher in infected pregnant women [(M0 p=0.001; M1 p=0.009; M2 p<0.0001 longitudinal) and (M0 p=0.03, M1 p=0.01 and M2 p=0.007 factorial)]. LPS dosages were higher in HIV+ pregnant women, than in HIV-pregnant women ( M0 p=0.0005, M1 p=0.0008 and M2 p=0.0001), which was even more expressive in the postpartum period, considering both models [(M2 p=0.0007 longitudinal) and (M2 p=0.004 factorial)]. Regarding sCD14, the longitudinal model showed higher dosages at the beginning of pregnancy (M0 p=0.02), while the factorial model showed no difference between HIVbut, considering only HIV+, these levels were higher in non-pregnant women (M0 p<0.0001. M1 p<0.0001 and M2 p<0.0001). For the EndoCAb of pregnant women, HIV+ presented higher IgA [(p=0.001 longitudinal) and (p=0.02 factorial)] and IgM [(p=0.02 longitudinal) and (p=0.03 factorial)] in the first gestational trimesters. While hiv-non-pregnant women had higher levels of IgA (p=0.02 factorial), HIV+ presented the highest values of IgM in the postpartum period, in relation to noninfected patients (p=0.05). Conclusion: Increased oxidative stress can occur in HIV-infected pregnant women, however, the virus is not solely responsible for this process, in which there seems to be involvement of other mechanisms related to pregnancy. The infection promoted greater microbial translocation and immune activation in HIV-infected, and pregnancy in turn decreased the latter in these women, as seen by LPS, sCD14, IgM and IgA.
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Palavras-chave
HIV/aids, Gestantes, Estresse oxidativo, Translocação microbiana, Ativação imune, Pregnant women, Oxidative stress, Microbial translocation, Immune activation