Enfermedad severa de inclusiones citomegálicas en un feto de una mujer inmunizada antes de la gestación / Severe cytomegalic inclusion disease in the fetus of a woman with preconceptional immunity

El descubrimiento de una microfelalia durante la gestación nos ha incitado a practicar una punción de líquido amniótico para análisis cromosómico y la búsqueda viral por reacción en cadena de la polimerasa (PCR). El análisis realizado ha confirmado una infección fetal por citomegalovirus (CMV) en una madre inmunizada antes de la concepción. El feto presentaba una clásica enfermedad de inclusiones citomegálicas. Se han publicado observaciones similares. Publicaciones recientes explican tales observaciones por la variabilidad de las cepas virales. Estos hechos incitan a estar atentos con los signos ecográficos evocadores de una infección viral en una mujer encinta ya inmunizada: se puede tratar de una reinfección por CMV

Due to detection of fetal microcephaly at 24 weeks' gestation, we performed an amniocentesis at 29 weeks with chromosomal analysis and polymerase chain reaction (PCR) to investigate the presence of viral contamination. Cytomegalovirus (CMV) infection was confirmed by PCR, although the mother had preconceptional CMV immunity. The fetus showed classical CMV inclusion disease. Recent publications explain similar observations by the variability of viral strains. These findings highlight the importance of being alert to ultrasonographic signs of CMV reinfection in pregnant women with preconceptual immunity

Expression of the third complement component (C3) and carboxypeptidase N small subunit (CPN1) during mouse embryonic development.

Complement regulatory proteins prevent excessive complement system activation and deposition, which can lead to host tissue damage, including fetal loss during pregnancy. To further understand the regulation of complement during development, we examined the expression of the complement protein, C3, and the active subunit of carboxypeptidase N (CPN1), the complement anaphylatoxin regulator. RNA and protein analyses indicated that CPN1 expression occurred as early as 8.5 days post coitus (dpc) and continued through birth. At 10.5 and 13.5 dpc, in situ hybridization revealed CPN1 RNA in erythroid progenitor cells. At 16.5 dpc, expression of CPN1 was also detected in hepatocytes. In comparison to CPN1, C3 RNA expression occurred later (after 13.5 dpc). Moreover, C3 expression was limited to the liver erythroid progenitor cells at 16.5 dpc. These results demonstrated that mouse embryos contain RNA and protein for both C3 and CPN1, and CPN1 expression precedes that of C3 by several days.

Markers of fetal growth and serum levels of insulin-like growth factor (IGF) I, -II and IGF binding protein 3 in adults.

Fetal growth has been linked with increased risk of cancer and cardiovascular disease later in life. The insulin-like growth factor (IGF) axis has recently been proposed as a predictor of risk of subsequent cancer and cardiovascular disease. However, only few data are available on the possible association between fetal growth and levels of IGFs later in life. We examined the association between markers of fetal growth, i.e. birth weight, birth length and Ponderal Index, from birth records and serum IGF-I, IGF-II, and IGF binding protein 3 (IGFBP-3) levels in 545 middle-aged Danish men and women. We fitted separate multivariate models including birth weight, birth length, Ponderal Index and serum IGF-I, IGF-II, and IGFBP-3, respectively. After adjustment for age, alcohol intake, smoking, diabetes mellitus, systolic and diastolic blood pressure, serum total cholesterol and current height and weight, we found negative associations between birth weight and Ponderal Index, respectively, and serum IGF-II in men, i.e. the mean regression coefficients were -49.41 (95% CI: -87.06-11.77) (microg/l)/kg and -3.49 (95% CI: -6.73-0.25) (microg/l)/(kg/m3), respectively. Furthermore, in men birth weight was negatively associated with the (IGF-I + IGF-II)/IGFBP-3 and IGF-II/IGFBP-3 ratios, which are believed to be indicators of bioavailable IGF and IGF-II, respectively. However, no other associations were found in any of the models. Between 1 and 16% of the variance in serum IGF-I, IGF-II, and IGFBP-3, respectively, could be explained by the statistical models used in the analyses. We found very little support to the hypothesis of an association between fetal growth and the IGF axis throughout life.

Antiphosphatidylserine antibodies affect rat yolk sacs in culture: a mechanism for fetal loss in antiphospholipid syndrome.

PROBLEM: A variety of reproductive impairments have been reported in the context of the antiphospholipid syndrome (APS). APS is associated with the presence of antibodies to negatively charged phospholipids that may affect the outcome of pregnancy. METHOD OF STUDY: Rat embryos were cultured within their yolk sacs. The effects of two antiphosphatidylserine monoclonal aPS antibodies (HL5B, RR7F) regarding their influence on growth and apoptotic events of the yolk sacs, as well as on growth and the morphology of the embryos, were studied. RESULTS: Exposure of rat embryos and their yolk sacs to aPS inhibited yolk sac growth. Moreover, increased number of apoptotic events of giant cells in the aPS-exposed ectoplacental cone was found in comparison with control IgG-exposed giant cells (P < 0.05). No significant damage was observed in the embryos. CONCLUSIONS: The results suggest that aPS affect growth and apoptosis of rat ectoplacental cone.

Lymphatic vasculature development.

Although the process of blood vasculature formation has been well documented, little is known about lymphatic vasculature development, despite its importance in normal and pathological conditions. The lack of specific lymphatic markers has hampered progress in this field. However, the recent identification of genes that participate in the formation of the lymphatic vasculature denotes the beginning of a new era in which better diagnoses and therapeutic treatment(s) of lymphatic disorders could become a reachable goal.

Human uterine leukocytes and pregnancy.

In human pregnancy, the embryo implants into the specialized mucosal wall of the uterus (decidua) and the placenta starts to form. Cells from the placenta (trophoblasts) invade into the uterine mucosa in order to open up maternal uterine arteries to ensure an adequate supply of blood to the developing fetus. The trophoblasts have a unique immunological phenotype compared to most cells especially with regard to their expression of major histocompatibility complex (MHC) antigens. On the other side of the interaction, the uterine mucosa (endometrium) differentiates in preparation for implantation. One of the changes that takes place is the appearance in the endometrium of a large number of maternal leukocytes in the final part of the menstrual cycle. If pregnancy ensues, these leukocytes continue to increase in number and are found in close contact with trophoblasts. The composition of this population of maternal immune cells is unusual compared to that seen at other mucosal sites. A lot of research has focused on whether maternal T-cell responses are suppressed or modified during pregnancy. Research has also concentrated on the specialized uterine natural killer (NK) cells, which are found in the decidua in large numbers during early pregnancy. These uterine NK cells have been shown to express receptors for trophoblast MHC antigens, but their role in pregnancy is still mysterious. The purpose of this review is to give an overview of what is known about the immunology at the implantation site and also to provide an update of some of the most recent findings in this field.

Effect of interleukin-10 null mutation on maternal immune response and reproductive outcome in mice.

Interleukin-10 (IL-10) is an anti-inflammatory and immune-deviating cytokine expressed in the endometrium and placenta. IL-10 null mutant (IL-10-/-) mice have been employed to examine the role of IL-10 in regulating immune events in early pregnancy and its significance in implantation and pregnancy success. The inflammatory response elicited in endometrial tissue by insemination was amplified in IL-10-/- mice, with a 66% increase in leukocytes in the endometrial stroma on Day 3 of pregnancy. Despite this, no evidence of abnormal type 1/type 2 skewing was seen in T-lymphocytes from lymph nodes draining the uterus. On Day 18 of gestation, IL-10-/- females mated with IL-10-/- males had 15% more implantation sites and 27% more viable fetuses than pregnant wild-type (IL-10+/+) mice. Placental weight was unaffected, but fetal weight and the fetal:placental weight ratio were higher in IL-10-/- pregnancies. Similar data were obtained in allogeneic pregnancies when IL-10-/- females were mated with major-histocompatibility complex (MHC) disparate IL-10-/- males. Pups delivered by IL-10-/- mothers had increased birth weight and followed an altered growth trajectory, with growth impairment evident from early postnatal life into adulthood, which was reflected in alterations in body composition at 14 wk of age. This study shows that although IL-10 is not essential for maternal immune tolerance or successful pregnancy irrespective of MHC disparity in the fetus, maternal IL-10 is a determinant of growth trajectory in progeny in utero and after birth.

An essential function for the nuclear receptor RORgamma(t) in the generation of fetal lymphoid tissue inducer cells.

Lymphoid tissue inducer (LTi) cells are associated with early development of lymph nodes and Peyer's patches. We show here that during fetal life the nuclear hormone receptor RORgamma(t) is expressed exclusively in and is required for the generation of LTi cells. RORgamma(t+) LTi cells provide essential factors, among which lymphotoxin-alpha1beta2 is necessary but not sufficient for activation of the mesenchyma in lymph node and Peyer's patch anlagen. This early LTi cell-mediated activation of lymph node and Peyer's patch mesenchyma forms the necessary platform for the subsequent development of mature lymphoid tissues.

Transcriptional control of murine CD94 gene: differential usage of dual promoters by lymphoid cell types.

The CD94 gene product is involved in controlling NK cell activation, and is one of a family of immune receptors that is found in the NK gene complex in both humans and mice, adjacent to members of the NKG2 family. CD94 forms a heterodimeric complex with several members of the NKG2 family on the surface of NK, T, and NKT cells. These complexes recognize the nonclassical MHC class I molecules HLA-E and Qa-1(b) in humans and mice, respectively. The mechanism for cell type-specific expression of CD94 and other genes from the NK gene complex has not yet been elucidated. In the current study, we show that the murine CD94 gene has two promoters, one of which is upstream of a previously unidentified exon. We illustrate by quantitative real-time PCR that lymphoid cell types use these two promoters differentially and that the promoter usage seen in adult cells is already established during fetal development. We determined that the differential promoter usage by NK cells appears to be susceptible to perturbation, as both the murine NK cell line LNK, as well as cultured C57BL/6 NK cells showed altered promoter usage relative to fresh NK cells. Furthermore, the promoter activity observed in transfection assays did not correlate with expression of the endogenous CD94 gene, suggesting the involvement of chromatin structure/methylation in transcriptional regulation. Our detection of DNase I hypersensitive sites at the CD94 locus that are present only in a cell line expressing endogenous CD94 supports this hypothesis.

Developmental immunology: clinical application to allergy-immunology.

BACKGROUND: An increase in prevalence of allergic diseases has been seen at an unprecedented rate in many countries throughout the world. Associated with this increase in allergic disease has been a disturbing increase in morbidity and mortality of such diseases as asthma despite the availability of several new therapeutic agents over the past 2 to 3 decades. The search for both environmental factors, eg, new allergens, as well as biologic markers of genetic susceptibility, eg, respiratory viruses, has yielded considerable promise for an explanation for this rising prevalence of allergic disease. OBJECTIVE: To present a central unifying hypothesis based upon recent knowledge concerning the developing human immune system and its interaction with external environmental factors, particularly viral infections, as a basis for a clearer understanding of the changing faces of the allergic diseases throughout the lifespan of the individual. DATA SOURCES: English language articles were selected from PubMed, as well as selected abstracts that would have immediate, practical clinical implications. RESULTS: Review of the current literature strongly suggests a relationship between delayed acquisition of Th1 function in the allergy-prone infant, not only as a predictive marker of susceptibility to the development of allergic disease but also as an explanation for the unique vulnerability of these infants to viral infection, eg, bronchiolitis. Furthermore, viral infection during early development in the allergy-prone infant appears to facilitate allergic sensitization in early infancy. This interesting triad of immune deficiency, viral infection, and atopic genetic susceptibility may provide a basis for early detection of allergic disease and may offer new intervention strategies for the prevention of allergic and infectious disease in the young infant.