VERONICA PORTO CARREIRO DE VASCONCELLOS COELHO
Projetos de Pesquisa
Unidades Organizacionais
Instituto do Coração, Hospital das Clínicas, Faculdade de Medicina - Médico
LIM/19 - Laboratório de Histocompatibilidade e Imunidade Celular, Hospital das Clínicas, Faculdade de Medicina - Líder
LIM/19 - Laboratório de Histocompatibilidade e Imunidade Celular, Hospital das Clínicas, Faculdade de Medicina - Líder
5 resultados
Resultados de Busca
Agora exibindo 1 - 5 de 5
- InhibitoryKIR2DL2Gene: Risk for Deep Endometriosis in Euro-descendants(2021) MARIN, Maria Lucia Carnevale; COELHO, Veronica; VISENTAINER, Jeane Eliete Laguila; ALVES, Hugo Vicentin; KOHLER, Karen Francine; RACHED, Marici Rached; ABRAO, Mauricio Simoes; KALIL, JorgeEndometriosis (EDT) is an inflammatory disease characterized by implantation/growth of endometrial tissue, glands, and/or stroma, outside the uterus. Reduced NK cell cytotoxic activity has been implicated in its pathogenesis, together with other immunologic alterations. We investigated the influence ofKIRgene polymorphisms and their HLA ligand combinations in deep endometriosis (DE) susceptibility. One hundred sixty women with a histological diagnosis of DE and 202 control women without the disease, who underwent laparoscopy, were enrolled. The DE group was subdivided into initial (I/II;n = 60) and advanced stages (III/IV,n = 100).KIRand HLA class I gene polymorphisms were typed by PCR-SSP and sequence-based-typing (SBT), respectively. We observed a significant association ofKIR2DL2, an inhibitory gene of B haplotype, conferring risk for DE in Euro-descendants. Positive associations of Bx haplotype and centromeric AB segments were also found. However, no association with KIR-HLA ligand combination was observed. Our data suggestKIR2DL2gene to be a relevant factor favoring NK inhibition in DE in Euro-descendants, contributing to the defective NK cytotoxic activity and impaired clearance of ectopic endometrial cells in the disease.
- Time-dependent contraction of the SARS-CoV-2–specific T-cell responses in convalescent individuals(2022) FERNANDES, E. R.; APOSTOLICO, J. de Souza; JACINTHO, L. C.; MARIN, M. L. Carnevale; JúNIOR, R. C. Vieira da Silva; RODRIGUES, H.; SANTOS, K. S.; COELHO, V.; BOSCARDIN, S. B.; KALIL, J.; CUNHA-NETO, E.; ROSA, D. S.Background: Adaptive immunity in severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection is decisive for disease control. Delayed activation of T cells is associated with a worse outcome in coronavirus disease 2019 (COVID-19). Although convalescent individuals exhibit solid T-cell immunity, to date, long-term immunity to SARS-CoV-2 is still under investigation. Objectives: We aimed to characterize the specific T-cell response on the basis of the in vitro recall of IFN-γ–producing cells to in silico–predicted peptides in samples from SARS-CoV-2 convalescent individuals. Methods: The sequence of the SARS-CoV-2 genome was screened, leading to the identification of specific and promiscuous peptides predicted to be recognized by CD4+ and CD8+ T cells. Next, we performed an in vitro recall of specific T cells from PBMC samples from the participants. The results were analyzed according to clinical features of the cohort and HLA diversity. Results: Our results indicated heterogeneous T-cell responsiveness among the participants. Compared with patients who exhibited mild symptoms, hospitalized patients had a significantly higher magnitude of response. In addition, male and older patients showed a lower number of IFN-γ–producing cells. Analysis of samples collected after 180 days revealed a reduction in the number of specific circulating IFN-γ–producing T cells, suggesting decreased immunity against viral peptides. Conclusion: Our data are evidence that in silico–predicted peptides are highly recognized by T cells from convalescent individuals, suggesting a possible application for vaccine design. However, the number of specific T cells decreases 180 days after infection, which might be associated with reduced protection against reinfection over time. © 2022 The Authors
conferenceObject Potential involvement of MICA (Major Histocompatibility Class I-related Chain A) in the pathogenesis of endometriosis(2016) MARIN, M. L. Carnevale; COELHO, V; RACHED, M. Rached; KALIL, J.; ABRAO, M. Simoes- HLA-G is upregulated in advanced endometriosis(2019) RACHED, Marici R.; COELHO, Veronica; MARIN, Maria Lucia C.; PINCERATO, Kstja; FUJITA, Andre; KALIL, Jorge E.; ABRAO, Mauricio S.Objective: To assess whether the HLA-G immunomodulatory protein is potentially involved in the pathophysiology of endometriosis or disease progression. Study design: Cross-sectional observational study of 227 women who underwent laparoscopy, being 146 for endometriosis excision and 81 for elective tubal ligation (control group). Soluble HLA-G (sHLA-G) levels in the serum and peritoneal fluid (PF), as well as the HLA-G protein expression in matched eutopic and ectopic endometrium of women with and without endometriosis were evaluated by ELISA and immunohistochemistry assays, respectively. Women with endometriosis were separated into groups according to the initial (I/II, n=60) and advanced (III/IV, n=86) stages of disease. sHLA-G measurement was performed only in women with matched serum and PF samples in both the control (CTRL; n=77) and endometriosis (EDT; I-II, n=60; n=83) groups. HLA-G protein expression was evaluated in 26 women with deep endometriosis (I-II, n=12; III-IV, n=14) and 22 controls. Results: Higher concentrations of sHLA-G (P=0.013) in the serum but not in the PF were observed in women with advanced endometriosis compared to the control group. In situ expression of HLA-G protein was also higher in ectopic (P=0.018) but not in eutopic endometrium of women with advanced endometriosis compared to control group. Conclusion: Our findings suggest that HLA-G upregulation in advanced stages may contribute to the state of immunosuppression in endometriosis as disease progresses.
- Soluble MICA in endometriosis pathophysiology: Impairs NK cell degranulation and effector functions(2024) MARIN, Maria Lucia Carnevale; RACHED, Marici Rached; MONTEIRO, Sandra Maria; KALIL, Jorge; ABRAO, Mauricio Simoes; COELHO, VeronicaProblem: Endometriosis exhibits several immune dysfunctions, including deficient natural killer (NK) cell cytotoxicity. MICA (MHC class I chain-related molecule A) is induced by biological stress and soluble MICA (sMICA) negatively modulates the expression of the activating receptor, NKG2D, reducing NK cells activities. We investigated the involvement of soluble MICA in NK cell-deficient activity in endometriosis. Methods of study: sMICA levels (serum and peritoneal fluid-PF) were evaluated by ELISA. Circulating NK cell subsets quantification and its NKG2D receptor expression, NK cell cytotoxicity and CD107a, IFN-gamma and IL-10 expressions by NK cells stimulated with K562 cells were determined by flow cytometry. Results: We found higher sMICA levels (serum and PF) in endometriosis, especially in advanced and deep endometriosis. Endometriosis presented lower percentages of CD56(dim)CD16+ cytotoxic cells and impaired NK cell responses upon stimulation, resulting in lower CD107a and IFN-gamma expressions, and deficient NK cell cytotoxicity. NK cell stimulation in the MICA-blocked condition (mimicking the effect of sMICA) showed decreased cytotoxicity in initial endometriosis stages and the emergence of a negative correlation between CD107a expression and sMICA levels. Conclusions: We suggest that soluble MICA is a potential player in endometriosis pathophysiology with involvement in disease progression and severity, contributing to NK cell impaired IFN-gamma response and degranulation. NK cell compartment exhibits multiple perturbations, including quantitative deficiency and impaired cytotoxicity, contributing to inadequate elimination of ectopic endometrial tissue.