RESUMO
Las mujeres embarazadas o en período de lactancia han sido excluidas de los ensayos clínicos sobre vacunas contra SARS-CoV-2, evitando así la obtención de datos sólidos que permitan determinar la seguridad e inmunogenicidad de las vacunas en esta población, a la vez que se han asociado peores resultados maternos fetales. La evidencia acerca de la seguridad e inmunogenicidad en esta población es limitada, en base a estudios observacionales, con pocos casos y en mujeres vacunadas con plataformas ARNm, en las cuales no se ha descrito por ahora una mayor asociación a eventos adversos relacionados a vacunas, como tampoco, variaciones significativas en la respuesta inmunológica en comparación a la población no embarazada. También existen datos que documentan la adquisición de anticuerpos transplacentarios, considerándose de bajo riesgo la posibilidad de transmisión vertical. Se hacen necesarios ensayos clínicos que permitan precisar recomendaciones basadas en evidencia para esta población, en un contexto de utilización de emergencia de vacunas contra SARS-CoV-2. (AU)
Pregnant or breastfeeding women have been excluded from clinical trials on vaccines against SARSCoV-2, thus avoiding obtaining solid data to determine the safety and immunogenicity of vaccines in this population, as well as being associated worse maternal-fetal outcomes. The evidence about safety and immunogenicity in this population is limited, based on observational studies, with few cases and in women vaccinated with mRNA platforms, in which a greater association to adverse events related to vaccines has not been described or significant variations in the immune response compared to the non-pregnant population. There are also data that document the acquisition of transplacental antibodies, considering the possibility of vertical transmission as low risk. Clinical trials are necessary to evidence-based recommendations for this population, in a context of emergency use of vaccines against SARSCoV-2. (AU)
Assuntos
Humanos , Feminino , Gravidez , Aleitamento Materno , Gravidez/imunologia , Vacinas contra COVID-19/efeitos adversos , Transmissão Vertical de Doenças Infecciosas/prevenção & controle , COVID-19/prevenção & controle , COVID-19/transmissãoRESUMO
Previously, we reported that the presence of multiple day 7 (D7) bovine embryos in the uterus induces systemic immune responses in circulating polymorphonuclear neutrophils (PMNs), but with unknown mechanism. Thus, this study aimed to investigate the direct impact of D7 bovine embryo on PMNs' immune responses in vitro and whether these PMNs can amplify and transfer embryo signals further to another PMN population. PMNs were directly stimulated by embryo culture media (ECM) or interferon tau (IFNT) (10 ng/ml) followed by evaluating mRNA expression by real-time PCR and phenotypic analysis by flow cytometry. To test whether PMNs can transfer embryo signals to a new PMN population, PMNs triggered by ECM or IFNT, were thoroughly washed and diluted to remove any media components, and again were incubated in fresh culture media for 3 h, from which culture supernatants were collected and used as PMN conditioned media (CM) to stimulate a new PMN population. Similar to ECM, IFNT directly stimulated expressions of IFNs (IFNA, IFNG), interferon-stimulated genes (ISGs; OAS1, ISG15, MX1), STAT1, TGFB and IL8, and downregulated TNFA in PMNs. Flow cytometrical analyses demonstrated that IFNT stimulated expressions of pregnancy-related phenotypic markers, CD16 and arginase-1 (ARG1), in PMNs. Most importantly, PMN CM induced ISGs and STAT1 mRNA in fresh PMNs. Since IFNT directly upregulated IFNA expression in PMNs, the impact of IFNA on PMNs' immune responses was further tested. Stimulation of PMNs with IFNA, especially at a low level (1 pg/ml), induced IFNT-like immune responses comparable to those induced by PMN CM. Together, these findings indicated that D7 bovine embryos induce direct anti-inflammatory responses with upregulation of ISGs expressions in PMNs mainly via IFNT. Additionally, PMNs can amplify and transfer embryo signals to a new PMN population in a cell-to-cell communication mechanism possibly mediated in part by IFNA. Such a novel immunological crosstalk might contribute to embryo tolerance and pregnancy establishment in cattle.
Assuntos
Embrião de Mamíferos/imunologia , Embrião de Mamíferos/metabolismo , Regulação da Expressão Gênica , Interferon Tipo I/imunologia , Neutrófilos/imunologia , Proteínas da Gravidez/imunologia , Gravidez/genética , Gravidez/imunologia , Animais , Arginase/genética , Bovinos , Meios de Cultivo Condicionados/farmacologia , Feminino , Regulação da Expressão Gênica/efeitos dos fármacos , Imunidade Inata , Técnicas In Vitro , Interferon Tipo I/farmacologia , Neutrófilos/efeitos dos fármacos , Neutrófilos/metabolismo , Fenótipo , Proteínas da Gravidez/farmacologia , Receptores de IgG/genéticaRESUMO
Circulating TFH (cTFH ) cells express CXCR5, PD-1, and, when activated, ICOS, and release IL-21. According to the production of IFN-γ, IL-4, and IL-17 and expression of FoxP3, these cells are also classified as cTFH 1, cTFH 2, cTFH 17, and cTFR cells, respectively. This CD4+ T-cell subset is pivotal to efficient humoral immunity, and pregnancy appears to favor IgG production. Here, not only pregnancy amplified the in vivo production of anti-HBsAg IgG in HBV immunized women, but the frequency of cTFH cells was directly correlated with estradiol levels. In vitro, pregnancy-related dose of 17-ß-estradiol (E2) directly increased the percentage of different cTFH subsets. While E2 and progesterone (P4) increased the proportion of differentiated TFH cells derived from naïve CD4+ T-cells, only E2 amplified the release of IL-21 in those cell cultures. In addition, E2 and P4 increased the proportion of memory B cells and plasma cells, respectively. In SEB-activated B/TFH cell co-cultures, E2, in the presence of P4, increased the production of total IgG. Finally, among the hormones, P4 was stronger in upregulating the percentage of IL-10+ TFR cells. Collectively, our findings suggested that E2 and P4 cooperate in the humoral immune response by favoring the expansion of different cTFH and B cell subsets.
Assuntos
Linfócitos B/imunologia , Estradiol/sangue , Estradiol/imunologia , Imunidade Humoral , Gravidez/sangue , Gravidez/imunologia , Progesterona/sangue , Progesterona/imunologia , Células T Auxiliares Foliculares/imunologia , Adulto , Subpopulações de Linfócitos B/efeitos dos fármacos , Subpopulações de Linfócitos B/imunologia , Diferenciação Celular , Citocinas/metabolismo , Estradiol/farmacologia , Feminino , Vacinas contra Hepatite B/imunologia , Humanos , Imunoglobulina G/biossíntese , Técnicas In Vitro , Interleucinas/biossíntese , Progesterona/farmacologia , Células T Auxiliares Foliculares/classificação , Células T Auxiliares Foliculares/citologia , Adulto JovemRESUMO
Women were studied undergoing ICSI for 84 who suffer non-pregnancy at the Fertility Center, Al-Sadr Medical Hospital in Najaf Governorate, Period between January 2019 and March 2020. WBC, Vitamin D3 and ß-hCG were measured, The pregnant women was divided into (Pregnancy Group, and spontaneous miscarriage) and then demonstrate the immunological effect on pregnancy of women after ICSI technique. Current resultsstudy showed a significant increase (p<0.05) in hormone level ß-hCG is evidence of the presence of high success rates for pregnancy in women who performed operations IVF, where the success rate at the beginning of the matter reached 61.9%, after which it decreased to 33.3% after the first three months due to the occurrence of spontaneous miscarriage of pregnant women due to various immunological and physiological reasons, a positive correlation between the level of ß-hCG and other parameters in the study (Vitamin D3 -WBC).Also The current resultsshowed a significant decrease in a groups (pregnancy failure) and the group (spontaneous miscarriage) compared with the control group (continued pregnancy) in relation to the level of vitamin D3 Also, The current results showed a significant increasein (pregnancy failure) and (spontaneous miscarriage) compared with control groups (continuation of pregnancy) in relation WBC numbers, and the present study founds a negative relationship between the level of vitamin D3 and WBC.
Assuntos
Humanos , Feminino , Gravidez/imunologia , Aborto Espontâneo/imunologia , Colecalciferol/deficiência , Injeções de Esperma Intracitoplásmicas/métodos , Gonadotropina Coriônica/imunologia , Leucócitos/imunologiaRESUMO
Interleukin-33 (IL-33) is a mucosal alarmin belonging to the IL-1 cytokine family and is now recognized to have a key role in innate and adaptive immunity, contributing to tissue homeostasis and response to environmental stresses. In addition, IL-33 has also been shown to work as a positive regulator that initiates and maintains a Th2 immune response. In the context of pregnancy, it has been recently demonstrated that upon certain stress conditions, such as an infection induced inflammation, IL-33 is released from the uterine mucosa and triggers decidual B cells to produce anti-inflammatory molecules, which in turn restore immune homeostasis and prevents the development of preterm birth. In this study we therefore performed a detailed characterization of IL-33 receptor (Il1rl1 or ST2) expression in B cells during normal pregnancy, as well as in a mouse model of preterm birth. We observed that splenic B cells significantly up-regulate the expression of Il1rl1 during pregnancy and identified the B1 B cell population as the main ST2-expressing B cell subset. A further kinetic analysis showed that percentages of ST2-expressing B1 B cells are significantly augmented on days 12 and 14 of pregnancy, both in the spleen and peritoneal cavity of pregnant mice, and then drop toward the end of pregnancy to the levels observed in non-pregnant animals. Furthermore, using a mouse model of LPS-induced preterm birth, we demonstrated that not only are the percentages of ST2-expressing B1 B cells significantly enlarged in the spleen during the acute phase of preterm birth, but decidual B cells also significantly up-regulate ST2 expression as compared to term-pregnant mice. Overall, our results suggest a functional role of ST2 expression in B cells during pregnancy and reinforce the importance of the IL-33/ST2 axis in B cells as a critical mechanism to control inflammation-induced preterm birth.
Assuntos
Subpopulações de Linfócitos B/imunologia , Linfócitos B/imunologia , Proteína 1 Semelhante a Receptor de Interleucina-1/metabolismo , Gravidez/imunologia , Nascimento Prematuro/imunologia , Doença Aguda , Animais , Modelos Animais de Doenças , Feminino , Regulação da Expressão Gênica , Humanos , Proteína 1 Semelhante a Receptor de Interleucina-1/genética , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Regulação para CimaRESUMO
Abstract Objective To describe the immunological and hematological reference intervals of low-risk pregnant women. Methods A cross-sectional retrospective database analysis of a basic and translational study analyzing the hematological evaluation blood counts and immunophenotyping of TCD3 + , TCD4 + , TCD8 + , B, and natural killer (NK) cells of the peripheral blood in 79 low-risk pregnant women and of 30 control women from the state of Pernambuco, Brazil, was performed. Results No significant differences were detected between the hematological profiles of the 2nd and 3rd trimesters. Nevertheless, the median level of B cells decreased significantly in the 2nd (174 x 103 μL; p < 0.002) and 3rd trimesters (160 x 103 μL; p < 0.001), compared with the control group (296 x 103 μL). Similarly, the median level of NK cells was lower in the 2nd (134 x 103 μL; p < 0.0004) and 3rd trimesters (100 x 103 μL, p < 0.0004), compared with the control group (183 x 103 μL). In contrast, relative TCD4+ and TCD8+ levels increased in the 2nd and 3rd trimesters compared with the controls (TCD4 + : 2nd trimester = 59%; p < 0.001; 3rd trimester = 57%; p < 0.01; control = 50%; and TCD8 + : 2nd trimester = 31%; p < 0.001; 3rd trimester = 36%; p < 0.01; control = 24%). Conclusion Low-risk pregnant women have ~ 40% less B and NK cells in the peripheral blood, compared with non-pregnant women. These parameters may improve health assistance for mothers and contribute to define reference values for normal pregnancies.
Resumo Objetivo Descrever o intervalo de referência imunológico e hematológico de gestantes de baixo risco. Métodos Realizou-se uma análise retrospectiva, de um estudo básico e translacional, analisando o perfil hematológico e a imunofenotipagem das células TCD3 + , TCD4 + , TCD8 + , B e natural killer (NK) do sangue periférico de 79 gestantes de baixo risco e de 30 mulheres (controles) do estado de Pernambuco, Brasil. Resultados Não observamos diferenças significativas entre os perfis hematológicos do 2° e 3° trimestres. No entanto, houve redução das células B no 2° (média = 174 x 103 μL; p < 0,002) e no 3° trimestres (160 x 103 μL; p < 0,001), comparado como grupo controle (296 x 103 μL). A mediana das células NK foi menor no 2° (134 x 103 μL; p < 0,0004) e no 3° trimestres (100 x 103 μL; p < 0,0004), comparado com o grupo controle (183 x 103 μL). Porém, o percentual de TCD4+ e de TCD8+ aumentou no 2° e 3° trimestres em relação aos controles (TCD4 + : 2° trimestre = 59%; p < 0,001; 3° trimestre = 57%; p < 0,01; controle = 50%; e TCD8 + : 2° trimestre = 31%; p < 0,001; 3° trimestre = 36%; p < 0,01; controle = 24%). Conclusão Mulheres grávidas de baixo risco têm ~ 40% menos células B e NK no sangue periférico em comparação com mulheres não grávidas. Estes parâmetros podem melhorar a assistência à saúde das mães e contribuir para a definição de valores de referência para gestações normais.
Assuntos
Humanos , Feminino , Adolescente , Adulto , Adulto Jovem , Gravidez/imunologia , Células Matadoras Naturais/fisiologia , Linfócitos T/fisiologia , Trimestres da Gravidez , Valores de Referência , Gravidez/sangue , Estudos Transversais , Estudos Retrospectivos , Bases de Dados FactuaisRESUMO
OBJECTIVE: To describe the immunological and hematological reference intervals of low-risk pregnant women. METHODS: A cross-sectional retrospective database analysis of a basic and translational study analyzing the hematological evaluation blood counts and immunophenotyping of TCD3 + , TCD4 + , TCD8 + , B, and natural killer (NK) cells of the peripheral blood in 79 low-risk pregnant women and of 30 control women from the state of Pernambuco, Brazil, was performed. RESULTS: No significant differences were detected between the hematological profiles of the 2nd and 3rd trimesters. Nevertheless, the median level of B cells decreased significantly in the 2nd (174 × 103 µL; p < 0.002) and 3rd trimesters (160 × 103 µL; p < 0.001), compared with the control group (296 × 103 µL). Similarly, the median level of NK cells was lower in the 2nd (134 × 103 µL; p < 0.0004) and 3rd trimesters (100 × 103 µL, p < 0.0004), compared with the control group (183 × 103 µL). In contrast, relative TCD4+ and TCD8+ levels increased in the 2nd and 3rd trimesters compared with the controls (TCD4 + : 2nd trimester = 59%; p < 0.001; 3rd trimester = 57%; p < 0.01; control = 50%; and TCD8 + : 2nd trimester = 31%; p < 0.001; 3rd trimester = 36%; p < 0.01; control = 24%). CONCLUSION: Low-risk pregnant women have â¼ 40% less B and NK cells in the peripheral blood, compared with non-pregnant women. These parameters may improve health assistance for mothers and contribute to define reference values for normal pregnancies.
OBJETIVO: Descrever o intervalo de referência imunológico e hematológico de gestantes de baixo risco. MéTODOS: Realizou-se uma análise retrospectiva, de um estudo básico e translacional, analisando o perfil hematológico e a imunofenotipagem das células TCD3 + , TCD4 + , TCD8 + , B e natural killer (NK) do sangue periférico de 79 gestantes de baixo risco e de 30 mulheres (controles) do estado de Pernambuco, Brasil. RESULTADOS: Não observamos diferenças significativas entre os perfis hematológicos do 2° e 3° trimestres. No entanto, houve redução das células B no 2° (média = 174 × 103 µL; p < 0,002) e no 3° trimestres (160 × 103 µL; p < 0,001), comparado com o grupo controle (296 × 103 µL). A mediana das células NK foi menor no 2° (134 × 103 µL; p < 0,0004) e no 3° trimestres (100 × 103 µL; p < 0,0004), comparado com o grupo controle (183 × 103 µL). Porém, o percentual de TCD4+ e de TCD8+ aumentou no 2° e 3° trimestres em relação aos controles (TCD4 + : 2° trimestre = 59%; p < 0,001; 3° trimestre = 57%; p < 0,01; controle = 50%; e TCD8 + : 2° trimestre = 31%; p < 0,001; 3° trimestre = 36%; p < 0,01; controle = 24%). CONCLUSãO: Mulheres grávidas de baixo risco têm â¼ 40% menos células B e NK no sangue periférico em comparação com mulheres não grávidas. Estes parâmetros podem melhorar a assistência à saúde das mães e contribuir para a definição de valores de referência para gestações normais.
Assuntos
Células Matadoras Naturais/fisiologia , Gravidez/imunologia , Linfócitos T/fisiologia , Adolescente , Adulto , Estudos Transversais , Bases de Dados Factuais , Feminino , Humanos , Gravidez/sangue , Trimestres da Gravidez , Valores de Referência , Estudos Retrospectivos , Adulto JovemRESUMO
Toxoplasmosis is a parasitic zoonosis distributed worldwide, caused by the ingestion of contaminated water/food with the parasite Toxoplasma gondii. If a pregnant woman is infected with this parasite, it may be transmitted to the fetus and produce ocular, neurological, or systemic damage with variable severity. The strength and profile of mother's immune response have been suggested as important factors involved in vertical transmission rate and severity of clinical outcome in the congenitally infected fetus. The aim of this work was to evaluate a possible relation between the mother's immune response during pregnancy and congenital transmission to the fetus. We obtained peripheral blood from T. gondii infected pregnant woman and tested it for anti T. gondii (IgG1, IgG2, IgG3, IgG4, and IgA) in serum. Peripheral blood mononuclear cells (PBMCs) were isolated to analyze the in vitro effect of soluble T. gondii antigens on proliferation and production of cytokines. We found that IgG2-4 and IgA antibodies and lymphocytes proliferation, especially CD4+, CD8+, and CD19+ were positive in a higher proportion of cases in transmitter than in non-transmitter women. Furthermore, IgG2-3 and IgA anti-Toxoplasma antibody levels were higher in those mothers who transmitted the infection than in those who did not. Interestingly, a higher proportion of positive cases to IFN-γ and negatives to the immunoregulatory cytokine TGF-ß, were related to T. gondii vertical transmission. Our descriptive results are consistent with the paradoxical previous observations in murine models of congenital toxoplasmosis, which suggest that an increased immune response that protects the mothers from a disseminated or severe disease, and should protect the fetus from infection, is positively related to parasite transmission.
Assuntos
Transmissão Vertical de Doenças Infecciosas , Gravidez/imunologia , Toxoplasmose/transmissão , Adolescente , Adulto , Citocinas/sangue , Feminino , Humanos , Imunoglobulina G/classificação , Ativação Linfocitária , Toxoplasmose/imunologia , Fator de Crescimento Transformador beta/fisiologia , Adulto JovemRESUMO
Cytokines are essential to maintain and coordinate the correct activity of immune cells during human pregnancy. IL-17 is a pro-inflammatory cytokine that induces the expression of many inflammatory mediators. The aim of this study was to compare the levels of Th1, Th2 and Th17 cytokines of women ongoing normal pregnancy with those found in women who suffered spontaneous abortion. IL-2, IL-4, IL-6, IL-10, IL-17, TNF-α, and IFN-γ peripheral blood levels were measured in women who suffered spontaneous abortion (n = 13, blood collected up to 24 h after abortion), and were compared with healthy successful pregnancies (n = 16). Cytokine levels were measured using a cytometric bead array (CBA analysis). Similar cytokine levels were observed between spontaneous abortion and healthy pregnant women excepted to IL-17, which levels were increased in the healthy pregnant women (p = 0.0232). Our results show high IL-17 levels in the peripheral blood of women at late stages of healthy pregnancy, although low IL-17 levels were detected in the peripheral blood of women just after spontaneous abortion. In line with recent studies, this finding highlights IL-17 as a regulatory cytokine essential to the maintenance of a successful pregnancy.