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1.
Gynecol Oncol ; 160(2): 450-456, 2021 02.
Artículo en Inglés | MEDLINE | ID: mdl-33213898

RESUMEN

OBJECTIVE: In 15% of patients with complete hydatidiform mole (CHM), disease progresses to post-molar gestational trophoblastic neoplasia (GTN) after curettage. Tumor infiltrating lymphocytes (TILs) are essential in overcoming disease in many tumors. Infiltrating lymphocyte composition and density may influence trophoblast regression and development of post-molar GTN. We analyzed immune cell composition and density in curettaged endometrium of patients with CHM which spontaneously regressed, and of patients with CHM which progressed to post-molar GTN. METHODS: Sixteen patients with CHM and spontaneous regression, and 16 patients with CHM which progressed to post-molar GTN were selected. Immune cell composition and density of natural killer (NK) cells, natural killer T (NKT)-like cells, Cytotoxic T cells, T-Regulatory and T-Helper cells, were determined by multiplex immunohistochemistry (mIHC). RESULTS: Curettaged endometrium of patients with CHM and spontaneous regression contained a slightly higher number of immune cells compared to patients with CHM which progressed to post-molar GTN. NKT-like cell density was significantly higher in patients with spontaneous regression compared to patients with CHM which progressed to post-molar GTN (483 ± 296 vs.295 ± 143 (mean ± SD), p = 0.03) respectively. NKT-like cell density in the spontaneous regression group was split in 'high' and 'low' (i.e. above and below the median number of NKT-like cells). In patients with high NKT-like cell density, hCG normalized earlier than in patients with low NKT-like cell density (9.5 weeks, (range 3.7-14) vs. 12.9 weeks, (range 8.6-17.9), p = 0.05). CONCLUSION: A high number of NKT-like cells in the endometrium of CHMs may contribute to spontaneous regression of molar trophoblast cells.


Asunto(s)
Endometrio/patología , Mola Hidatiforme/inmunología , Linfocitos Infiltrantes de Tumor/inmunología , Células T Asesinas Naturales/inmunología , Neoplasias Uterinas/inmunología , Adulto , Gonadotropina Coriónica/sangre , Legrado , Progresión de la Enfermedad , Endometrio/citología , Endometrio/inmunología , Endometrio/cirugía , Femenino , Citometría de Flujo , Estudios de Seguimiento , Edad Gestacional , Humanos , Mola Hidatiforme/sangre , Mola Hidatiforme/patología , Mola Hidatiforme/cirugía , Inmunofenotipificación , Persona de Mediana Edad , Embarazo , Estudios Retrospectivos , Neoplasias Uterinas/sangre , Neoplasias Uterinas/patología , Neoplasias Uterinas/cirugía , Adulto Joven
2.
Am J Reprod Immunol ; 84(5): e13310, 2020 11.
Artículo en Inglés | MEDLINE | ID: mdl-32698238

RESUMEN

The emergence of coronavirus disease 2019 (COVID-19) as a pandemic threatens the entire world resulting in severe consequences for people's health. Pregnant patients with COVID-19 had immune dysregulation that could result in abnormal pregnancy outcomes such as hydatidiform mole (HM), recurrent pregnancy loss, and early-onset preeclampsia. In this article, we tried to summarize the possible association between COVID-19 and the HM's development by reviewing the role of NOD-Like Receptor (NLR) Family Pyrin Domain Containing 7 (NLRP7), cytokines, zinc, and leukocytes in the pathogenesis of HM.


Asunto(s)
COVID-19/inmunología , Mola Hidatiforme/inmunología , Leucocitos/inmunología , Complicaciones Infecciosas del Embarazo/inmunología , SARS-CoV-2/fisiología , Proteínas Adaptadoras Transductoras de Señales/metabolismo , Citocinas/metabolismo , Femenino , Humanos , Pandemias , Embarazo , Resultado del Embarazo
3.
Clin Exp Immunol ; 202(1): 72-79, 2020 10.
Artículo en Inglés | MEDLINE | ID: mdl-32484253

RESUMEN

NOD-like receptor pyrin 7 (NLRP7) has been identified as the major gene responsible for the recurrent hydatidiform mole (RHM). The immunological role of NLRP7 mutation in HM patients has not been conclusively demonstrated. Hence, we aim to demonstrate this role in our study. We followed 12 new patients with NLRP7 non-synonymous variations (NSVs) from date to date. Peripheral blood mononuclear cells (PBMCs) were collected separately from patients with and without NLRP7 mutation. Supernatant interleukin (IL)-1ß secretion, intracellular pro-IL-1ß and mature IL-1ß expressions were measured after 24 h lipopolysaccharide (LPS) stimulation. Plasmids with corresponding NSVs were generated to evaluate the ability of processing pro-IL-1ß into mature IL-1ß in vitro. Homozygous or compound heterozygous NLRP7 mutations secreted less IL-1ß in roots of abnormal intracellular pro-IL-1ß or mature IL-1ß, according to different domains. Plasmids with NSVs could also affect processing or/and trafficking together with caspase-1 and apoptosis-associated speck-like protein (ASC). Inflammasome-related NLRP7 mutation is a potential mechanism of RHM.


Asunto(s)
Proteínas Adaptadoras Transductoras de Señales , Mola Hidatiforme , Interleucina-1beta , Leucocitos Mononucleares/inmunología , Mutación , Proteínas de Neoplasias , Proteínas Adaptadoras Transductoras de Señales/genética , Proteínas Adaptadoras Transductoras de Señales/inmunología , Adulto , Femenino , Estudios de Seguimiento , Células HEK293 , Humanos , Mola Hidatiforme/genética , Mola Hidatiforme/inmunología , Interleucina-1beta/genética , Interleucina-1beta/inmunología , Leucocitos Mononucleares/patología , Proteínas de Neoplasias/inmunología , Embarazo
4.
Int J Mol Sci ; 20(20)2019 Oct 10.
Artículo en Inglés | MEDLINE | ID: mdl-31658584

RESUMEN

Gene expression studies of molar pregnancy have been limited to a small number of candidate loci. We analyzed high-dimensional RNA and protein data to characterize molecular features of complete hydatidiform moles (CHMs) and corresponding pathologic pathways. CHMs and first trimester placentas were collected, histopathologically examined, then flash-frozen or paraffin-embedded. Frozen CHMs and control placentas were subjected to RNA-Seq, with resulting data and published placental RNA-Seq data subjected to bioinformatics analyses. Paraffin-embedded tissues from CHMs and control placentas were used for tissue microarray (TMA) construction, immunohistochemistry, and immunoscoring for galectin-14. Of the 14,022 protein-coding genes expressed in all samples, 3,729 were differentially expressed (DE) in CHMs, of which 72% were up-regulated. DE genes were enriched in placenta-specific genes (OR = 1.88, p = 0.0001), of which 79% were down-regulated, imprinted genes (OR = 2.38, p = 1.54 × 10-6), and immune genes (OR = 1.82, p = 7.34 × 10-18), of which 73% were up-regulated. DNA methylation-related enzymes and histone demethylases were dysregulated. "Cytokine-cytokine receptor interaction" was the most impacted of 38 dysregulated pathways, among which 17 were immune-related pathways. TMA-based immunoscoring validated the lower expression of galectin-14 in CHM. In conclusion, placental functions were down-regulated, imprinted gene expression was altered, and immune pathways were activated, indicating complex dysregulation of placental developmental and immune processes in CHMs.


Asunto(s)
Mola Hidatiforme/genética , Mola Hidatiforme/inmunología , Placenta/metabolismo , Embarazo/inmunología , Coriocarcinoma , Citocinas , Metilación de ADN , Regulación hacia Abajo , Femenino , Expresión Génica , Enfermedad Trofoblástica Gestacional , Humanos , Inmunohistoquímica , Primer Trimestre del Embarazo , Biología de Sistemas , Regulación hacia Arriba
5.
Gynecol Obstet Invest ; 73(2): 106-12, 2012.
Artículo en Inglés | MEDLINE | ID: mdl-22269478

RESUMEN

INTRODUCTION: Trophoblast cells cooperate with both maternal immune cells and decidual cells to help develop the suppressive microenvironment of the endometrium. The maternal immune response against hydatidiform mole depends on this suppressive endometrial profile. Since RCAS1 is one of the molecular factors participating in the development of the suppressive profile of the endometrium we decided to examine the immunoreactivity of the RCAS1 within both the trophoblast and decidual cells during the development of hydatidiform mole. METHODS: We analyzed the immunoreactivity of RCAS1 on both trophoblast and decidual cells derived from patients who underwent curettage because of hydatidiform mole. These patients were then divided into two subgroups according to whether or not they required chemotherapy after the surgical procedure. RESULT: We observed significantly lower immunoreactivity levels of both RCAS1 within the complete molar lesions of the patients on whom surgery alone was performed when compared to the levels found in those for whom surgery was followed by chemotherapy. CONCLUSION: RCAS1 staining may provide information regarding the intensity of the immunosuppressive microenvironment of both the molar lesion and the endometrium. This information can prove significant in determining the clinical course of hydatidiform mole.


Asunto(s)
Antígenos de Neoplasias/inmunología , Decidua/inmunología , Mola Hidatiforme/inmunología , Mola Hidatiforme/terapia , Neoplasias Uterinas/inmunología , Neoplasias Uterinas/terapia , Quimioterapia Adyuvante , Decidua/efectos de los fármacos , Femenino , Humanos , Mola Hidatiforme/tratamiento farmacológico , Mola Hidatiforme/cirugía , Inmunohistoquímica , Embarazo , Complicaciones Neoplásicas del Embarazo , Neoplasias Uterinas/tratamiento farmacológico , Neoplasias Uterinas/cirugía
7.
Mol Med Rep ; 5(1): 275-81, 2012 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-22002546

RESUMEN

Hydatidiform moles are considered pre-cancerous lesions of gestational trophoblastic neoplasia and are associated with an aberrant immune response. This preliminary study aimed to evaluate the feasibility of measuring the presence of immune cells as potential prognostic markers for hydatidiform moles. Immunohistochemical staining of FoxP3⁺ regulatory T cells, CD3⁺ T cells, CD56⁺ decidual natural killer cells and Ki-67⁺ trophoblast cells was performed on 32 samples. Samples were from complete hydatidiform moles, partial hydatidiform moles, ectopic pregnancies, gestational age-matched normal elective pregnancy terminations (normal pregnancies) and gestational trophoblastic neoplasias. FoxP3⁺ regulatory T-cell infiltration was highest in the complete hydatidiform moles and lowest in the normal pregnancy samples. The normal pregnancy cases showed significantly fewer FoxP3⁺ regulatory T cells compared to the ectopic pregnancy cases (p=0.037) and compared to the combination of all of the other groups (p=0.044). Normal pregnancy samples also showed the lowest infiltration of CD3⁺ T cells and the highest number of CD56⁺ decidual natural killer cells; conversely, gestational trophoblastic neoplasias showed the highest infiltration of CD3⁺ T cells and the lowest number of CD56⁺ decidual natural killer cells. The numbers of Ki-67⁺ trophoblast cells were highest in the gestational trophoblastic neoplasias (688/1,000 trophoblast cells) and lowest in the partial moles (87/1,000 trophoblast cells). Our results suggest that regulatory T cells may be involved in the progression of complete hydatidiform moles. A larger cohort study is required to assess whether immune cells are effective prognostic markers in gestational trophoblastic diseases.


Asunto(s)
Decidua/inmunología , Mola Hidatiforme/inmunología , Células Asesinas Naturales/inmunología , Embarazo Ectópico/inmunología , Linfocitos T Reguladores/inmunología , Linfocitos T/inmunología , Trofoblastos/inmunología , Adolescente , Adulto , Complejo CD3/metabolismo , Antígeno CD56/metabolismo , Decidua/metabolismo , Femenino , Factores de Transcripción Forkhead/metabolismo , Humanos , Mola Hidatiforme/patología , Inmunohistoquímica , Antígeno Ki-67/metabolismo , Embarazo , Primer Trimestre del Embarazo , Trofoblastos/citología , Adulto Joven
8.
Am J Reprod Immunol ; 65(2): 164-72, 2011 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-20645939

RESUMEN

INTRODUCTION: The suppressive microenvironment developing around the implantating ovum in normal pregnant women may correlate with the development in cancer patients of a suppressive microenvironment of neoplasmatic cells derived from trophoblasts, such as occurs in molar lesions. Macrophages are suitable candidates for mediating not only the balance of the maternal defensive immune responses to external antigens, but also a tolerance to tumor cells. The aim of our study has been to gain information about the expression of RCAS1, B7H4, and HLA-G within the macrophages present in the microenvironment of the molar lesion. METHODS: We analyzed the immunoreactivity of such antigens as B7H4, RCAS1, and HLA-G on the macrophages present in tissue samples derived from patients on whom curettage was performed after a diagnosis of molar pregnancy. These patients were then divided into two subgroups according to whether or not they required chemotherapy after the surgical procedure. RESULTS: We observed a statistically significant increase in the RCAS1-positive macrophage infiltration within the microenvironment of the molar lesions in patients with partial hydatidiform mole in comparison with those patients who exhibited complete hydatidiform mole. There were no such differences, however, in the infiltration of HLA-G- and B7H4-positive macrophages between the two groups of patients. Additionally, we showed that RCAS1- and HLA-G-positive macrophages are more distinct in those cases of complete molar pregnancy where chemotherapy was necessary after surgical treatment while no such differences with respect to B7H4-positive macrophages were observed. CONCLUSION: The immune-suppressive endometrial microenvironment represented by suppressive macrophages may have an influence on the clinical course of hydatidiform mole.


Asunto(s)
Antígenos de Neoplasias/metabolismo , Antígeno B7-1/metabolismo , Antígenos HLA/metabolismo , Antígenos de Histocompatibilidad Clase I/metabolismo , Mola Hidatiforme/inmunología , Macrófagos/inmunología , Neoplasias Uterinas/inmunología , Femenino , Antígenos HLA-G , Humanos , Mola Hidatiforme/tratamiento farmacológico , Mola Hidatiforme/cirugía , Inmunohistoquímica , Macrófagos/metabolismo , Embarazo/inmunología , Neoplasias Uterinas/tratamiento farmacológico , Neoplasias Uterinas/cirugía
9.
J Reprod Med ; 55(5-6): 261-6, 2010.
Artículo en Inglés | MEDLINE | ID: mdl-20626184

RESUMEN

OBJECTIVE: Advanced maternal age may result in a weaker immune response against complete molar pregnancy, therefore increasing the risk of gestational trophoblastic neoplasia due to ineffective elimination of the trophoblastic cells after evacuation. The present study was undertaken to investigate the cellular immune response against complete molar pregnancy at the implantation site in younger and older patients. STUDY DESIGN: Immunolocalization of CD8, granzyme B (GrB), FoxP3 and CD56 was performed on histologic tissue sections prepared from 18 patients aged < or = 40 years and 10 patients aged > 40 years to characterize effector (GrB+CD8+) cytotoxic T cells, GrB positive and negative natural killer cells (CD56) and regulatory T cells (FoxP3+) at the implantation site in complete molar pregnancies. RESULTS: The number of the different immune cell types did not show significant differences in the implantation sites of complete molar pregnancies between the 2 age groups or between persistent and nonpersistent cases. CONCLUSION: Immunosenescence of the natural killer and T cells most likely does not play a role in the increased incidence of gestational trophoblastic neoplasia in older patients with complete moles.


Asunto(s)
Mola Hidatiforme/inmunología , Inmunidad Celular/inmunología , Edad Materna , Neoplasias Uterinas/inmunología , Adulto , Recuento de Células , Femenino , Humanos , Embarazo
10.
Transfusion ; 50(5): 1126-30, 2010 May.
Artículo en Inglés | MEDLINE | ID: mdl-20030792

RESUMEN

BACKGROUND: The involvement of the human platelet antigen (HPA)-15 system in neonatal alloimmune thrombocytopenia (NAIT) has been reported in various populations, but not in the Japanese population. In Japan, the mixed passive hemagglutination assay (MPHA) is used for detection of HPA alloantibodies. However, most of the reported cases of HPA-15 incompatibility are based on the monoclonal antibody immobilization of platelet antigen (MAIPA) assay or immunoprecipitation; thus there is a possibility that HPA-15 alloantibodies are not efficiently detected by the MPHA, and currently, the causative antibody is not detectable in approximately half of the suspected NAIT cases in Japan. STUDY DESIGN AND METHODS: We examined the sera of mothers from NAIT cases, previously with undetected HPA antibodies by MPHA, using the MAIPA technique. Sera from 90 mothers of suspected NAIT were tested by MAIPA for the presence of anti-HPA-15 alloantibodies. RESULTS: Anti-HPA-15b was detected in one case. This case was a mother in the first pregnancy diagnosed as hydatid mole-coexisting fetus, and the baby was born with suspected NAIT. The familial analysis revealed compatibility of HPA-15 genotype between the mother and the baby (both HPA-15a/a), but incompatibility with the paternal one (HPA-15a/b). The hydatid mole's tissue was genotyped as HPA-15b positive. Besides anti-HPA-15b, maternal sera contain strong HLA Class I antibody CONCLUSIONS: Here we reported the first case of anti-HPA-15 in Japan. Alloimmunization against the hydatid mole seems to be responsible for the production of HPA-15b alloantibody. This antibody, however, did not apparently involve in the development of NAIT of the newborn, the coexisting anti-HLA Class I being the possible cause.


Asunto(s)
Antígenos CD/inmunología , Mola Hidatiforme/inmunología , Isoanticuerpos/sangre , Proteínas de Neoplasias/inmunología , Trombocitopenia Neonatal Aloinmune/inmunología , Neoplasias Uterinas/inmunología , Femenino , Proteínas Ligadas a GPI , Pruebas de Hemaglutinación , Humanos , Embarazo
11.
Cancer Invest ; 27(1): 60-6, 2009 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-19160109

RESUMEN

BACKGROUND: Hydatidiform mole is a gestational trophoblastic disease characterized by proliferation of the pregnancy-associated trophoblastic tissue. Complete hydatidiform mole is an entirely paternally derived lesion, and therefore, represents complete intrauterine allografts that can induce an altered maternal immune response Hypothesis: Here, we hypothesize that "the development of hydatidiform moles is associated with numeric alterations of the decidual immune cell infiltrate." MATERIALS AND METHODS: A total of 30 specimens (decidual tissue), entailing normal first trimester pregnancy terminations and complete hydatidiform moles (15 cases, each), were evaluated for immune cell infiltrate using immunohistological methods and monoclonal antibodies (CD20, CD68, and CD3 for B cells, histiocytes/dendritic cells, and T cells, respectively). RESULTS: Groups of immune cells were seen in the decidual tissue of first trimester normal pregnancy terminations and hydatidiform moles. Compared to the decidual tissue of first trimester normal pregnancy terminations, the mean counts of the immune cells were statistically significantly higher (p< 0.05) in the decidual tissue of the hydatidiform moles (0.33 +/- 0.21 vs. 1.66 +/- 0.21 for CD20(+)B cells; 9.80 +/- 1.57 vs. 13.14 +/- 1.16 for CD68(+) cells; and 12.92 +/- 3.46 vs. 23.85 +/- 1.22 for CD3(+) cells for decidual tissue without and with molar changes, respectively). CONCLUSIONS: Hydatidiform moles are associated with numeric alterations of immune cell infiltrate. The numeric dominance of immune cells in the hydatidiform moles may reflect either non-specific or specific immunological processes. The possible pathogenetic and prognostic ramifications of our findings are open for further investigations.


Asunto(s)
Linfocitos B/inmunología , Decidua/inmunología , Mola Hidatiforme/inmunología , Linfocitos T/inmunología , Neoplasias Uterinas/inmunología , Adulto , Antígenos CD/inmunología , Antígenos CD20/inmunología , Antígenos de Diferenciación Mielomonocítica/inmunología , Complejo CD3/inmunología , Recuento de Células , Decidua/metabolismo , Decidua/patología , Células Dendríticas/inmunología , Femenino , Histiocitos/inmunología , Humanos , Mola Hidatiforme/patología , Técnicas para Inmunoenzimas , Embarazo , Primer Trimestre del Embarazo , Estudios Prospectivos , Linfocitos T/patología , Neoplasias Uterinas/patología , Adulto Joven
12.
Asian Pac J Allergy Immunol ; 26(2-3): 171-81, 2008.
Artículo en Inglés | MEDLINE | ID: mdl-19054936

RESUMEN

Human pregnancy is a complex process. Placental development depends on the function of secretory molecules produced by placental trophoblast cells as well as by maternal uterine immune cells within the decidua. These decidual immune cells are T cells, natural killer cells, macrophages and dendritic cells. The interactions between the trophoblast cells and the maternal immune cells have an impact on the outcome of the pregnancy. Knowledge about the phenotypes and functions of the maternal immune cells in normal and pathological pregnancies including recurrent spontaneous abortions, preeclampsia and hydatidiform moles may improve our understanding of the immunobiology of the normal pregnancy as a whole and may provide approaches for improving the treatment of pathological pregnancies.


Asunto(s)
Aborto Habitual/inmunología , Decidua/inmunología , Mola Hidatiforme/inmunología , Inmunidad Celular , Preeclampsia/inmunología , Embarazo/inmunología , Aborto Habitual/sangre , Decidua/irrigación sanguínea , Decidua/crecimiento & desarrollo , Femenino , Humanos , Mola Hidatiforme/sangre , Circulación Placentaria/inmunología , Placentación/inmunología , Preeclampsia/sangre , Trofoblastos/inmunología , Útero/patología
13.
J Reprod Med ; 53(8): 558-64, 2008 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-18773618

RESUMEN

OBJECTIVE: To determine the level of infiltration and antigen profile of immune cells and explore their relationship in intraplacental and postmolar choriocarcinoma to better understand the immunobiology of choriocarcinoma. STUDY DESIGN: Immunolocalization of CD8, Granzyme B (GrB) and FoxP3 was performed on sections prepared from 5 intraplacental and 7 postmolar choriocarcinomas to characterize effector Tc cells (GrB+, CD8+) and GrB- (GrB-, CD8+) Tc cells, GrB+ NK cells (GrB+, CD8-) and Treg (FoxP3+) cells. RESULTS: In the case of intraplacental choriocarcinoma, immune cell infiltration was not detected in the surrounding villi or in the tumor. Immune cell infiltration into the implantation site of the placenta with intraplacental choriocarcinoma did not differ from that into the normal pregnancy implantation site. In postmolar choriocarcinoma the immune cell infiltration of the adjacent tissue was vigorous and involved all types of immune cells (Tc, NK, Treg). In 6 of 7 cases of postmolar choriocarcinoma, in spite of the vigorous immune response, immune cells could not be seen in the choriocarcinoma tissue. A sharp infiltration border of immune cells was noted at the edge of the postmolar choriocarcinoma tissue. CONCLUSION: Intraplacental choriocarcinoma is not associated with a vigorous immune cell response. In contrast, postmolar choriocarcinoma is associated with a vigorous immune cell response in adjacent tissues but not the choriocarcinoma tissue itself.


Asunto(s)
Mola Hidatiforme/inmunología , Tumor Trofoblástico Localizado en la Placenta/inmunología , Neoplasias Uterinas/inmunología , Estudios de Cohortes , Femenino , Humanos , Células Asesinas Naturales/inmunología , Embarazo , Linfocitos T Citotóxicos/inmunología , Linfocitos T Reguladores/inmunología
14.
J Reprod Med ; 53(7): 528-34, 2008 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-18720929

RESUMEN

OBJECTIVE: To investigate the antigenicity of normal placenta and complete molar trophoblastic tissue. STUDY DESIGN: T cell receptor (TCR) variable beta chain (VBC) gene expression was analyzed utilizing fresh frozen tissues. Real-time polymerase chain reactions (RT-PCR) were performed on cDNA samples from 10 normal buffy coats (BC), 7 normal placentas (NP) and 14 complete molar pregnancies (CM) using a TCR beta chain and 25 variable TCR beta chain primers. Relative expressions were calculated for each individual gene. RESULTS: Significant changes were noted in most of the gene expressions in NP and CM as compared to the buffy coat samples. The relative expression of most genes was significantly decreased in NP and CM, but VBC gene number 4 was increased in both NP and CM; however, a significant difference was noted only between BC and CM (p = 0.023). Comparing NP to CM, 5 other VBC gene expressions were decreased significantly in the CM tissues (p < 0.05). CONCLUSION: In normal placenta and CM pregnancies, T cells appear to express certain TCR VBC genes in a different manner than in BC. These genes and the VBC gene profile difference found between NP and CM may play an important role in the immunobiology of CM pregnancy.


Asunto(s)
Antígenos/inmunología , Mola Hidatiforme/inmunología , Placenta/inmunología , Embarazo/inmunología , Receptores de Antígenos de Linfocitos T alfa-beta/inmunología , Receptores de Antígenos de Linfocitos T/inmunología , Antígenos/genética , Femenino , Expresión Génica , Humanos , Mola Hidatiforme/genética , Receptores de Antígenos de Linfocitos T/genética , Receptores de Antígenos de Linfocitos T alfa-beta/genética , Linfocitos T/inmunología
15.
J Histochem Cytochem ; 56(5): 477-85, 2008 May.
Artículo en Inglés | MEDLINE | ID: mdl-18256018

RESUMEN

Glycodelin (Gd) is a major reproductive glycoprotein and a mediator for immunomodulatory effects directed to cellular, humoral, and innate immunity. Human pregnancy depends on a diversity of physiological processes including modulation of the maternal immunosystem. We evaluated the expression of Gd protein and mRNA in first trimester decidual tissue of normal pregnancies and spontaneous abortion and hydatidiform moles. Furthermore, in vitro experiments on endometrial cancer cells to analyze the effect of human chorionic gonadotropin (hCG) on Gd regulation were performed. In decidual tissue of abortion patients, Gd expression was significantly decreased compared with normal gestation, which was confirmed by in situ hybridization. In mole pregnancy, an upregulation of Gd in the first 8 weeks of pregnancy was present. Gd is a main product of decidual tissue in the first trimester of human pregnancy. Reduced Gd expression in abortive pregnancy could lead to an increased activation of the maternal immunosystem, thus causing rejection of the developing fetus. Moreover, Gd expression in endometrial cancer cells in vitro could be stimulated by addition of hCG. Therefore, we speculate that hCG could be one of the factors regulating Gd expression because hCG is downregulated in women with abortion and upregulated in mole pregnancy. In addition, we found a positive feedback loop in Gd and hCG expression in human pregnancy.


Asunto(s)
Aborto Espontáneo/genética , Regulación hacia Abajo , Regulación Neoplásica de la Expresión Génica , Glicoproteínas/genética , Mola Hidatiforme/genética , Proteínas Gestacionales/genética , Primer Trimestre del Embarazo/genética , Regulación hacia Arriba , Aborto Espontáneo/inmunología , Aborto Espontáneo/metabolismo , Anticuerpos Monoclonales/inmunología , Especificidad de Anticuerpos , Línea Celular Tumoral , Gonadotropina Coriónica/genética , Gonadotropina Coriónica/metabolismo , Femenino , Glicodelina , Humanos , Mola Hidatiforme/inmunología , Mola Hidatiforme/metabolismo , Hibridación in Situ , Embarazo , Primer Trimestre del Embarazo/inmunología , Primer Trimestre del Embarazo/metabolismo , ARN Mensajero/genética , ARN Mensajero/metabolismo
16.
Placenta ; 29 Suppl A: S92-4, 2008 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-18037165

RESUMEN

Between 11% and 20% of all clinically recognised pregnancies are lost before the 20th week of gestation, with huge financial and personal implications. Immune mechanisms have been proposed to play a role in unexplained recurrent miscarriage. Considerable attention has focused on endometrial leucocyte populations in recurrent miscarriage, although the underlying pathogenesis remains largely unexplained. The mechanisms underlying sporadic miscarriage are even less well understood, although aneuploidy is the commonest attributable cause of early (

Asunto(s)
Aborto Espontáneo/patología , Mola Hidatiforme/patología , Útero/patología , Aborto Espontáneo/inmunología , Aborto Espontáneo/metabolismo , Educación , Femenino , Humanos , Mola Hidatiforme/inmunología , Mola Hidatiforme/metabolismo , Estrés Oxidativo , Embarazo , Útero/inmunología , Útero/metabolismo
17.
Gynecol Oncol ; 107(2): 292-7, 2007 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-17878059

RESUMEN

OBJECTIVES: Cytotoxic T cells (Tc) and natural killer (NK) cells may play a role in controlling trophoblast invasion. This study was undertaken to determine the level of infiltration and antigen profile of immune cells and explore their relationship in normal placenta (NP) and molar tissues to better understand the biology of gestational trophoblastic diseases. MATERIALS AND METHODS: Immunolocalization of CD8, Granzyme B (GrB), and FoxP3 was performed on sections prepared from 11 gestational age-matched NP, 19 partial moles (PM), and 18 complete moles (CM) to characterize effector (GrB+CD8+) and GrB- (GrB-CD8+) Tc cells, GrB+ NK cells (GrB+CD8-), and Treg (FoxP3+) cells. RESULTS: Immune cells infiltrated into the implantation site of normal placenta, PM, and CM with increasing frequency. Effector and GrB- Tc, GrB+ NK and Treg infiltration in the CM were significantly stronger than seen in the normal placenta (p=0.002, p=0.007, p=0.002, respectively). Immune cell infiltration was not detected in the villi or trophoblast of gestational tissues. Treg infiltration in the implantation site was only observed in PM and CM. In CM and PM Tc infiltration positively correlated with Treg infiltration (p=0.035), but Treg infiltration did not correlate with the Tc effector ratio (effector Tc cells/all Tc cells). CONCLUSION: In CM the cellular immune response in the implantation site was significantly more vigorous than seen in normal placenta. These observations demonstrate that in the implantation site of CM, the number of effector Tc and GrB+ NK cells are increased and Treg cells may negatively regulate T lymphocyte activation.


Asunto(s)
Mola Hidatiforme/inmunología , Embarazo/inmunología , Linfocitos T/inmunología , Neoplasias Uterinas/inmunología , Adulto , Antígenos CD8/análisis , Linfocitos T CD8-positivos/inmunología , Femenino , Factores de Transcripción Forkhead/análisis , Granzimas/análisis , Humanos , Mola Hidatiforme/química , Células Asesinas Naturales/inmunología , Activación de Linfocitos , Linfocitos T Reguladores/inmunología , Neoplasias Uterinas/química
18.
Diagn Mol Pathol ; 14(3): 164-9, 2005 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-16106198

RESUMEN

Complete hydatidiform moles (CHMs) are a type of androgenetic fertilization without an ovum. Cases of CHM exhibit a generalized swelling of the villi and are known to be highly associated with persistent disease or carcinoma. In contrast, partial hydatidiform moles (PHMs) also show characteristic hydropic changes among the villi, but the incidence of secondary disease is relatively low. Because PHMs are fertilized by one ovum and two sperm and CHMs are fertilized by one or two sperm alone, we considered whether or not maternally imprinted genes might be useful for achieving a differential diagnosis. The validity of the imprinted genes in CHMs was assessed by implementation of a microarray technique. Among the genes examined, TSSC3, SLC22A1L, KCNQ1, and Decorin were shown to be down-regulated, and TSSC3 was the most markedly suppressed of these genes. In this study, 20 cases of CHM, the diagnosis of which was confirmed by DNA polymorphism, were investigated. In all of these cases, the expression of TSSC3 was completely absent, as determined by Western blot analysis. Conversely, 12 cases of PHM, also diagnosed by DNA polymorphism, were examined here; in all of these 12 cases, TSSC3 was found to be expressed normally. Immunohistochemical (IHC) analysis also produced the same results. The complete silencing of TSSC3 in cases of CHM will provide a novel, convenient strategy for the diagnosis of molar lesions in the placenta.


Asunto(s)
Anticuerpos , Mola Hidatiforme/diagnóstico , Proteínas Nucleares/análisis , Proteínas Nucleares/inmunología , Western Blotting , Decorina , Diagnóstico Diferencial , Proteínas de la Matriz Extracelular , Femenino , Regulación de la Expresión Génica , Humanos , Mola Hidatiforme/genética , Mola Hidatiforme/inmunología , Inmunohistoquímica , Proteínas de la Membrana/genética , Proteínas Nucleares/genética , Análisis de Secuencia por Matrices de Oligonucleótidos , Proteínas de Transporte de Catión Orgánico/genética , Canales de Potasio con Entrada de Voltaje/genética , Embarazo , Complicaciones del Embarazo/diagnóstico , Proteoglicanos/genética
19.
Anticancer Res ; 25(3A): 1725-30, 2005.
Artículo en Inglés | MEDLINE | ID: mdl-16033091

RESUMEN

UNLABELLED: The persistence of polymorphic trophoblastic hyperplasia in a hydatidiform mole is an extremely rare condition. Its early diagnosis is essential since such cases can transform into invasive tumours. MATERIALS AND METHODS: The paraffin-embedded biopsies were routinely stained with HE. Immunohistochemical staining reactions were performed with monoclonal antibodies against inhibin-alpha, inhibin-betaA and inhibin-betaB subunits. Additional immunohistochemical reaction was performed with, Sialyl-Lewis A and Sialyl-Lewis X and glycodelin. RESULTS: Large villi and hydatidiform villi with ranging syncyctio- and cytotrophoblasts were seen. Intervillous proliferating trophoblasts showed cell- and nuclear polymorphy with invasion of the myometrium wall. The immunohistochemistry exhibited strong positivity for inhibin-alpha, inhibin-betaA and inhibin-betaB subunits in trophoblastic tissue, while the decidua was negative. Sialyl-Lewis A and Sialyl-Lewis X showed no or minimal focal immunohistochemical reaction. CONCLUSION: A complete hydatidiform mole with hyperplasia and proliferation presents a high risk of developing a persistent (eventually metastatic) trophoblastic disorder and, in up to 15% of the cases, an invasive mole. In 2.5% of the cases it can transform into a choriocarcinoma. Since the inhibin/activin subunits reacted positively with trophoblastic tissue, they might be a useful diagnostic marker for hydatidiform mole with persistence of polymorphic trophoblastic hyperplasia.


Asunto(s)
Activinas/metabolismo , Antígeno CA-19-9/inmunología , Mola Hidatiforme/metabolismo , Hiperplasia/metabolismo , Inhibinas/metabolismo , Oligosacáridos/inmunología , Trofoblastos/metabolismo , Adulto , Femenino , Humanos , Mola Hidatiforme/inmunología , Hiperplasia/inmunología , Inmunohistoquímica , Embarazo , Antígeno Sialil Lewis X , Trofoblastos/inmunología
20.
Clin Exp Immunol ; 138(2): 330-6, 2004 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-15498045

RESUMEN

Complete hydatidiform moles are totally paternally derived and represent complete allografts that might be expected to provoke maternal immune rejection. Our previous and other studies have shown expression of Fas by increased numbers of activated decidual CD4(+) T cells in both complete and partial molar pregnancy as well as increased FasL(+) expression by molar trophoblasts compared with trophoblasts in normal pregnancies. As the Fas/FasL system represents a major apoptotic pathway that can play a role in immune privilege, the aim of this study was to investigate whether apoptosis of decidual immune cells, particularly T cells, could be responsible for maternal immune tolerance in molar pregnancy. Using terminal deoxynucleotidyl transferase (TdT)-mediated nick end-labelling (TUNEL), a significant increase in TUNEL(+) cells was demonstrated in decidua associated with partial (P = 0.0052) and complete (P = 0.0096) hydatidiform mole compared with normal early pregnancy. Co-labelling immunoperoxidase studies showed that the TUNEL(+) cells in both normal and molar pregnancies were not activated CD45RO(+) immune cells, CD3(+) T cells, CD56(+) uterine natural killer (NK) cells or CD14(+) CD68(+) macrophages. Double immunohistochemical labelling with antiactive caspase-3 and leucocyte markers confirmed the lack of leucocyte apoptosis. Double immunostaining with anticytokeratin to detect trophoblast and M30 CytoDeath, which detects a neoepitope of cytokeratin 18 revealed after caspase-mediated cleavage, revealed apoptotic extravillous trophoblast cells within decidual tissue. We conclude that there is no evidence that apoptosis of decidual leucocytes plays a role in maintaining maternal tolerance in either normal or molar pregnancy.


Asunto(s)
Apoptosis/inmunología , Decidua/inmunología , Mola Hidatiforme/inmunología , Tolerancia Inmunológica/inmunología , Leucocitos/inmunología , Neoplasias Uterinas/inmunología , Antígenos CD/análisis , Caspasa 3 , Caspasas/análisis , Decidua/patología , Precursores Enzimáticos/análisis , Femenino , Humanos , Técnicas para Inmunoenzimas/métodos , Etiquetado Corte-Fin in Situ/métodos , Queratinas/análisis , Células Asesinas Naturales/inmunología , Embarazo , Linfocitos T/inmunología
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