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Showing papers by "Juan Pedro Kusanovic published in 2012"


Journal ArticleDOI
TL;DR: Nearly half of the patients with late-onset PE have placental lesions consistent with maternal underperfusion, which are associated with an imbalance in the maternal concentration of angiogenic/anti-angiogenic factors.
Abstract: Objective: An imbalance between maternal angiogenic/anti-angiogenic factors concentrations has been observed in preeclampsia (PE) and other obstetrical syndromes. However, the frequency of pathologic findings in the placenta and the changes in maternal plasma angiogenic/anti-angiogenic factor concentrations differ between late- and early-onset PE. The aim of this study was to determine if the maternal plasma concentrations of placental growth factor (PlGF), soluble endoglin (sEng), and soluble vascular endothelial growth factor receptor-1 and 2 (sVEGFR-1 and sVEGFR-2) are different in late-onset PE with and without placental pathologic findings consistent with maternal underperfusion. Study design: A cross-sectional study was conducted including 64 uncomplicated women and 66 women with late-onset PE (>34 weeks) who had blood samples and placenta available for pathologic examination. Patients with late-onset PE were divided into those with and without placental histologic findings consistent with maternal ...

141 citations



Journal ArticleDOI
TL;DR: The hematologic profile of the human fetus with FIRS is characterized by significant changes in the total WBC and neutrophil counts, and the NRBC count in fetuses with FIRs tends to be higher than fetuses without FIRS.
Abstract: OBJECTIVE The fetal inflammatory response syndrome (FIRS) is associated with impending onset of preterm labor/delivery, microbial invasion of the amniotic cavity and increased perinatal morbidity FIRS has been defined by an elevated fetal plasma interleukin (IL)-6, a cytokine with potent effects on the differentiation and proliferation of hematopoietic precursors The objective of this study was to characterize the hematologic profile of fetuses with FIRS STUDY DESIGN Fetal blood sampling was performed in patients with preterm prelabor rupture of membranes and preterm labor with intact membranes (n=152) A fetal plasma IL-6 concentration ≥ 11 pg/mL was used to define FIRS Hemoglobin concentration, platelet count, total white blood cell (WBC) count, differential count, and nucleated red blood cell (NRBC) count were obtained Since blood cell count varies with gestational age, the observed values were corrected for fetal age by calculating a ratio between the observed and expected mean value for gestational age RESULTS 1) The prevalence of FIRS was 289% (44/152); 2) fetuses with FIRS had a higher median corrected WBC and corrected neutrophil count than those without FIRS (WBC: median 14, range 03-56, vs median 11, range 04-29, P=0001; neutrophils: median 36, range 01-575, vs median 18, range 02-139, P 95th centile of gestational age) was significantly more common in fetuses with FIRS than in those without FIRS (71%, 30/42, vs 35%, 37/105; P<0001); 4) more than two-thirds of fetuses with FIRS had neutrophilia, whereas neutropenia was present in only 48% (2/42); 5) FIRS was not associated with detectable changes in hemoglobin concentration, platelet, lymphocyte, monocyte, basophil or eosinophil counts; and 6) fetuses with FIRS had a median corrected NRBC count higher than those without FIRS However, the difference did not reach statistical significance (NRBC median 007, range 0-13, vs median 004, range 0-23, P=006) CONCLUSION The hematologic profile of the human fetus with FIRS is characterized by significant changes in the total WBC and neutrophil counts The NRBC count in fetuses with FIRS tends to be higher than fetuses without FIRS

60 citations


Journal ArticleDOI
TL;DR: Peripheral CD300a+CD8+ T lymphocytes with a distinct cytotoxic molecular signature increase in pregnant women with chronic chorioamnionitis is observed.
Abstract: Citation Xu Y, Tarquini F, Romero R, Kim CJ, Tarca AL, Bhatti G, Lee J, Sundell IB, Mittal P, Kusanovic JP, Hassan SS, Kim J-S. Peripheral CD300a+CD8+ T lymphocytes with a distinct cytotoxic molecular signature increase in pregnant women with chronic chorioamnionitis. Am J Reprod Immunol 2012; 67: 184–197 Problem CD300a is an immunomodulatory molecule of the immunoglobulin receptor superfamily expressed in the leukocytes of myeloid and lymphoid lineages. However, its biological function on CD8+ T lymphocytes remains largely unknown. This study was conducted to assess the biological significance of CD300a expression in T lymphocytes and to determine whether its expression in peripheral T lymphocytes changes in pregnant women presenting with antifetal rejection. Methods of Study Microarray analysis was performed using total RNA isolated from peripheral CD300a+ and CD300a− T lymphocytes. Flow cytometric analysis of the peripheral blood samples of pregnant women and pathologic examination of the placentas were conducted. Results A large number of genes (N = 1245) were differentially expressed between CD300a− and CD300a+ subsets of CD8+ T lymphocytes, which included CCR7, CD244, CX3CR1, GLNY, GZMB, GZMK, IL15, ITGB1, KLRG1, PRF1, and SLAMF7. Gene ontology analysis of differentially expressed genes demonstrated enrichment of biological processes such as immune response, cell death, and signal transduction. CD300a expression in CD8+ T lymphocytes was coupled to a more cytotoxic molecular signature. Of note, the proportion of CD300a+CD8+ T lymphocytes increased in pregnant women with chronic chorioamnionitis (antifetal rejection of the chorioamniotic membranes; P < 0.05). Conclusion The findings of this study strongly suggest an increase in systemic T-lymphocyte-mediated cytotoxicity in pregnant women with chronic chorioamnionitis as a manifestation of maternal antifetal rejection.

45 citations


Journal ArticleDOI
TL;DR: IL-19 and IL-10 are parts of the immunologic response of FIRS, and in utero exposure to high systemic concentrations of IL-19 may reprogram the immune response.
Abstract: Objective: The fetal inflammatory response syndrome (FIRS) is considered the fetal counterpart of the systemic inflammatory response syndrome (SIRS), which can be caused by infection and non-infection-related insults. Although the initial response is mediated by pro-inflammatory signals, the control of this response is achieved by anti-inflammatory mediators which are essential for the successful outcome of the affected individual. Interleukin (IL)-19 is capable of stimulating the production of IL-10, a major anti-inflammatory cytokine, and is a potent inducer of the T-helper 2 (Th2) response. The aim of this study was to determine if there is a change in umbilical cord plasma IL-19 and IL-10 concentrations in preterm neonates with and without acute funisitis, the histologic counterpart of FIRS. Methods: A case-control study was conducted including 80 preterm neonates born after spontaneous labor. Neonates were classified according to the presence (n = 40) or absence of funisitis (n = 40), which is the pa...

23 citations


Journal ArticleDOI
TL;DR: In this paper, maternal varicella-zoster immunoglobulin administration before rash development, with or without antiviral medication, can modify the progression of the disease and prevent the spread of the virus.
Abstract: Congenital varicella syndrome, maternal varicella-zoster virus pneumonia and neonatal varicella infection are associated with serious fetomaternal morbidity and, not infrequently, mortality. Vaccination against varicella-zoster virus can prevent the disease, and outbreak control limits the exposure of pregnant women to the infectious agent. Maternal varicella-zoster immunoglobulin administration before rash development, with or without antiviral medication, can modify the progression of the disease.

23 citations