ENDOTHELIAL, IMMUNOLOGICAL AND STRUCTURAL ASSESSMENT OF PLACENTAL SPECIMENS FROM T. cruzi VERTICAL TRANSMISSION CASES IN SANTA CRUZ DE LA SIERRA – BOLIVIA

Placenta;Chagas Disease;Vertical transmission;Biomarkers;Epidemiology

Galdos Cardenas, Gerson DarioScott, Alan L. ;

Johns Hopkins University

关键词: Placenta;    Chagas Disease;    Vertical transmission;    Biomarkers;    Epidemiology;   

Others  :  https://jscholarship.library.jhu.edu/bitstream/handle/1774.2/40834/GALDOSCARDENAS-DISSERTATION-2017.pdf?sequence=1&isAllowed=y

瑞士|英语

来源: JOHNS HOPKINS DSpace Repository

【 摘 要 】

The role of the placenta in the vertical transmission of T. cruzi, as well as the risk factors that contribute to vertical transmission, are not well defined.. Few studies have evaluated the use of the placenta for diagnosis of Chagas disease in newborns. Accurate identification of infected newborns is a high priority in control programs since the cure rates are high. Using immunohistochemistry, we evaluated endothelial and structural impairment of placental cells, as well as features of the immune response that may be contributors in congenital Chagas disease.Immunohistochemistry markers of disturbed placental barrier were standardized and matched to obstetrical and neonatal data. No differences were found in placental measurements of neonatal and obstetrical characteristics in cases of vertical transmission. Conventional testing, achieved diagnosis after 6 months of age. In contrast, TESA-blot and quantitative polymerase-chain reaction (q-PCR) (on cord blood or umbilical tissue) identified the majority of cases at birth. Successful immunohistochemistry techniques were identified for further evaluation.We also assessed placental barrier impairment linked to endothelial cells and dysfunctional endothelial tight junction’ proteins using markers of angiogenesis.Expression of endothelial tight junction proteins was increased at fetal blood vessels and decreased at syncytiotrophoblast. Markers of angiogenesis showed decreased expression at the placental barrier. Dysregulated angiogenesis and impaired cell-to-cell contact at the syncytiotrophoblast layer are related to placental barrier impairment and may be associated with congenital infection. The expression of structural proteins was increased in fetal blood vessels and the syncytiotrophoblast, while the expression of tight junction proteins was decreased in the cytotrophoblast. Expression of mediators of innate immune response was increased in the syncytiotrophoblast and fetal blood vessels. Expression of markers of macrophage activation was decreased in the syncytiotrophoblast. Increased expression of structural proteins at the syncytiotrophoblast is related to impaired placental barrier and may be associated with T. cruzi vertical transmission. In conclusion, molecular tests for diagnosis of congenital Chagas Disease should be implemented in poor resource settings. Signs of impaired placental barrier and immune response are documented in this study. Future research identifying placental biomarkers at maternal serum would be very useful for perinatal diagnosis.