VERONICA PORTO CARREIRO DE VASCONCELLOS COELHO

(Fonte: Lattes)
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Lattes
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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

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Autor: COELHO, Veronica ×

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Agora exibindo 1 - 10 de 26
  • article 13 Citação(ões) na Scopus
    UPLC-MS/MS assay validation for tacrolimus quantitative determination in peripheral blood T CD4+and B CD19+lymphocytes
    (2018) ROMANO, Paschoalina; FERNANDES, Maria da Luz; EBNER, Persio de Almeida Rezende; OLIVEIRA, Nayara Duarte de; OKUDA, Larissa Mitsue; AGENA, Fabiana; MENDES, Maria Elizabete; SUMITA, Nairo Massakazu; COELHO, Veronica; DAVID-NETO, Elias; GALANTE, Nelson Zocoler
    Monitoring tacrolimus (Tac) exposure in cell matrices enriched with lymphocytes can improve Tac therapeutic drug monitoring (TDM) in solid organ transplant recipients. An UPLC-MS/MS based assay for Tac quantification in peripheral blood T CD4+ and B CD19+ lymphocytes was developed. Peripheral blood mononuclear cells (PBMC) were obtained by density gradient centrifugation and highly purified (purity >90%) T CD4+ and B CD19+ cell suspensions were acquired by magnetic negative selection from whole blood of 6 healthy volunteers. The purity of lymphocyte suspensions was checked by flow cytometry. Tac extraction was performed in a liquid-liquid zinc sulfate, methanol and acetonitrile based medium. Ascomycin was used as internal standard. The equipment used was a Waters (R) Acquity (TM) UPLC system (Waters Corporation, Milford, MA, USA). The chromatographic run was performed on a Waters (R) MassTrak TDM C18 (2.1 x 10 mm) column (Waters Corporation, Milford, MA, USA). at a flow rate of 0.4 mL/min. The instrument was set in electrospray positive ionization mode. The method was validated according to Clinical Laboratory Standard Institute (CLSI) guidelines and showed a high sensitivity and specificity over a range of 0-5.2 ng/mL in PBMC, 0-5.0 ng/mL in T CD4+ Lymphocytes and 0-5.3 ng/mL in B CD19+ lymphocytes. Precision was appropriate with CV of intra-assay quantifications ranging from 4.9 to 7.4%, and of inter-assay quantifications from 7.2 to 13.9%. Limit of detection and quantification were 0.100 and 0.115 ng/mL in PBMC, 0.058 and 0.109 ng/mL in T CD4+ and 0.017 and 0.150 ng/mL in B CD19+ cells. Matrix effect was not significant among all the studied matrices. Samples showed stability for Tac quantification over a period of 90 days either at room temperature or at -30 degrees C storage conditions. The method was applied to clinical samples of 20 kidney transplant recipients. Concentrations ranged from 2.200 to 11.900 ng/mL in whole blood, from 0.005 to 0.570 ng/10(6) cells in PBMC, from 0.081 to 1.432 ng/10(6) cells in T CD4+, and from 0.197 to 1.564 ng/10(6) cells in B CD19+ cell matrices. The method has potential applicability for Tac TDM in solid organ transplant recipients.
  • article 1 Citação(ões) na Scopus
    Regulatory/inflammatory cellular response discrimination in operational tolerance
    (2019) CARMONA, Priscila; MEDINA-ARMENTEROS, Yordanka; CABRAL, Amanda; MONTEIRO, Sandra Maria; FONSECA, Simone Goncalves; FARIA, Ana Caetano; LEMOS, Francine; SAITOVITCH, David; NORONHA, Irene L.; KALIL, Jorge; COELHO, Veronica
    Background. Antigen-specific cellular response is essential in immune tolerance. We tested whether antigen-specific cellular response is differentially modulated in operational tolerance (OT) in renal transplantation with respect to critical antigenic challenges in allotransplantation-donor antigens, pathogenic antigens and self-antigens. Methods. We analysed the profile of immunoregulatory (REG) and pro-inflammatory (INFLAMMA) cytokines for the antigen-specific response directed to these three antigen groups, by Luminex. Results. We showed that, in contrast to chronic rejection and healthy individuals, OT gives rise to an immunoregulatory deviation in the cellular response to donor human leucocyte antigen DR isotype peptides, while preserving the pro-inflammatory response to pathogenic peptides. Cellular autoreactivity to the N6 heat shock protein 60 (Hsp60) peptide also showed a REG profile in OT, increasing IL4, IL-5, IL-10 and IL-13. Conclusions. The REG shift of donor indirect alloreactivity in OT, with inhibition of interleukin (IL)-1B, IL-8, IL-12, IL-17, granulocyte colony-stimulating factor, Interferon-gamma and monocyte chemoattractant protein-1, indicates that this may be an important mechanism in OT. In addition, the differential REG profile of cellular response to the Hsp60 peptide in OT suggests that REG autoimmunity may also play a role in human transplantation tolerance. Despite cross-reactivity of antigen-specific T cell responses, a systemic functional antigen-specific discrimination takes place in OT.
  • article 19 Citação(ões) na Scopus
    Rethinking the multiple roles of B cells in organ transplantation
    (2013) COELHO, Veronica; SAITOVITCH, David; KALIL, Jorge; SILVA, Hernandez Moura
    Purpose of review To discuss the B-cell diverse functions in organ transplantation, highlighting the emerging debate on the role of regulatory B cells (Bregs). We underscore the need to re-examine and integrate data on B-cell functional activities, aiming to discriminate their regulatory (REG) and inflammatory (INFLAMMA) functions and to translate this knowledge for the development of novel immunomodulatory therapeutic strategies and to rethink the current ones. Recent findings Data from both experimental models and clinical trials point that B cells of various phenotypes have immunoregulatory activity and play an important role in controlling graft inflammation. Data on the state of operational tolerance, in kidney transplantation, suggest the relevance of preserving a healthy B-cell compartment - in numbers and in the Breg capacity to activate the CD40/STAT3 signalling pathway - for achieving and maintaining homeostasis. Moreover, autoantibodies also comprise transplant immunobiology and it seems that not all alloantibodies are deleterious. Summary The role of B cells, in organ transplantation, can no longer be taken as mere generators of plasma cells, which produce alloantibodies deleterious to the graft. B cells also seem to integrate a complex immunoregulatory network in organ transplantation, with Bregs of various phenotypes and possibly also antibodies. The functional discrimination of REG/INFLAMMA B-cell roles needs to be considered in the clinical setting.
  • article 77 Citação(ões) na Scopus
    Preserving the B-Cell Compartment Favors Operational Tolerance in Human Renal Transplantation
    (2012) SILVA, Hernandez M.; TAKENAKA, Maisa C. S.; MORAES-VIEIRA, Pedro M. M.; MONTEIRO, Sandra M.; HERNANDEZ, Maristela O.; CHAARA, Wahiba; SIX, Adrien; AGENA, Fabiana; SESTERHEIM, Patricia; BARBE-TUANA, Florencia Maria; SAITOVITCH, David; LEMOS, Francine; KALIL, Jorge; COELHO, Veronica
    Transplanted individuals in operational tolerance (OT) maintain long-term stable graft function after completely stopping immunosuppression. Understanding the mechanisms involved in OT can provide valuable information about pathways to human transplantation tolerance. Here we report that operationally tolerant individuals display quantitative and functional preservation of the B-c ell compartment in renal transplantation. OT exhibited normal numbers of circulating total B cells, naive, memory and regulatory B cells (Bregs) as well as preserved B-cell receptor repertoire, similar to healthy individuals. In addition, OT also displayed conserved capacity to activate the cluster of differentiation 40 (CD40)/signal transducer and activator of transcription 3 (STAT3) signaling pathway in Bregs, in contrast, with chronic rejection. Rather than expansion or higher activation, we show that the preservation of the B-cell compartment favors OT. Online address: http://www.molmed.org doi: 10.2119/molmed.2011.00281
  • article 11 Citação(ões) na Scopus
    MMP9 integrates multiple immunoregulatory pathways that discriminate high suppressive activity of human mesenchymal stem cells
    (2017) LAVINI-RAMOS, Carolina; SILVA, Hernandez Moura; SOARES-SCHANOSKI, Alessandra; MONTEIRO, Sandra Maria; FERREIRA, Ludmila Rodrigues Pinto; PACANARO, Ana Paula; GOMES, Samirah; BATISTA, Janaina; FAE, Kellen; KALIL, Jorge; COELHO, Veronica
    The mechanisms underlying mesenchymal stem cells' (MSC) suppressive potency are largely unknown. We here show that highly suppressive human adipose tissue-derived MSC (AdMSC) display and induce a differential immunologic profile, upon ongoing AdMSC suppressive activity, promoting: (i) early correlated inhibition of IFN-gamma and TNF-alpha production, along IL-10 increase, (ii) CD73(+) Foxp3(+) Treg subset expansion, and (iii) specific correlations between gene expression increases, such as: MMP9 correlated with CCL22, TNF, FASL, RUNX3, and SEMAD4 in AdMSC and, in T cells, MMP9 upregulation correlated with CCR4, IL4 and TBX21, among others, whereas MMP2 correlated with BCL2 and LRRC31. MMP9 emerged as an integrating molecule for both AdMSC and T cells in molecular networks built with our gene expression data, and we confirmed upregulation of MMP9 and MMP2 at the protein level, in AdMSC and T cells, respectively. MMP2/9 inhibition significantly decreased AdMSC suppressive effect, confirming their important role in suppressive acitivity. We conclude that MMP9 and 2 are robust new players involved in human MSC immunoregulatory mechanisms, and the higher suppressive activity correlates to their capacity to trigger a coordinated action of multiple specific molecules, mobilizing various immunoregulatory mechanisms.
  • article 32 Citação(ões) na Scopus
    Aging and End Stage Renal Disease Cause A Decrease in Absolute Circulating Lymphocyte Counts with A Shift to A Memory Profile and Diverge in Treg Population
    (2019) FREITAS, Geraldo Rubens Ramos; FERNANDES, Maria da Luz; AGENA, Fabiana; JALUUL, Omar; SILVA, Sergio Colenci; LEMOS, Francine Brambate Carvalhinho; COELHO, Veronica; DAVID-NETO, Elias; GALANTE, Nelson Zocoler
    There is a growing number of elderly kidney transplant (Ktx) recipients. Elderly recipients present lower acute rejection rates but higher incidence of infection and malignancies. Aging per se seems to result in a shift to memory profile and chronic kidney disease (CKD) in premature immunological aging. Understanding aging and CKD effects on the immune system can improve elderly Ktx immunosuppression. We analyzed the effects of aging and CKD in the immune system, comparing healthy adults (HAd) (n=14, 26 +/- 2y), healthy elderly (HEld) (n=15, 79 +/- 7y), end stage renal disease (ESRD) adults (EnAd) (n=18, 36 +/- 7y) and ESRD elderly (EnEld) (n=31, 65 +/- 3y) prior to Ktx regarding their naive, memory and regulatory T and B peripheral lymphocytes. Aging and ESRD presented additive effect decreasing absolute numbers of B and T-lymphocytes, affecting memory, naive and regulatory subsets without synergic effect. Both resulted in higher percentages of T memory subsets and opposing effects on regulatory T (TREG) subsets, higher percentage in aging and lower in ESRD. Combined effect of aging and ESRD also resulted in higher regulatory B cell percentages. In addition to global lymphopenia and TCD4(+) memory shift in both aging and ESRD, aging shifts to an immunoregulatory profile, inducing a increase in TREG percentages, contrasting with ESRD that decreases TREGs. Differential immunosuppression regimens for elderly Ktx may be required.
  • article 9 Citação(ões) na Scopus
    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, Jorge
    Endometriosis (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.
  • article 5 Citação(ões) na Scopus
    Immunodominant antibody responses directed to SARS-CoV-2 hotspot mutation sites and risk of immune escape
    (2023) OLIVEIRA, Jamille Ramos; RUIZ, Cesar Manuel Remuzgo; MACHADO, Rafael Rahal Guaragna; MAGAWA, Jhosiene Yukari; DAHER, Isabela Pazotti; URBANSKI, Alysson Henrique; SCHMITZ, Gabriela Justamante Haendel; ARCURI, Helen Andrade; FERREIRA, Marcelo Alves; SASAHARA, Greyce Luri; MEDEIROS, Giuliana Xavier de; JR, Roberto Carlos Vieira Silva; DURIGON, Edison Luiz; BOSCARDIN, Silvia Beatriz; ROSA, Daniela Santoro; SCHECHTMAN, Deborah; NAKAYA, Helder. I. I.; CUNHA-NETO, Edecio; GADERMAIER, Gabriele; KALIL, Jorge; COELHO, Veronica; SANTOS, Keity Souza
    IntroductionConsidering the likely need for the development of novel effective vaccines adapted to emerging relevant CoV-2 variants, the increasing knowledge of epitope recognition profile among convalescents and afterwards vaccinated with identification of immunodominant regions may provide important information. MethodsWe used an RBD peptide microarray to identify IgG and IgA binding regions in serum of 71 COVID-19 convalescents and 18 vaccinated individuals. ResultsWe found a set of immunodominant RBD antibody epitopes, each recognized by more than 30% of the tested cohort, that differ among the two different groups and are within conserved regions among betacoronavirus. Of those, only one peptide, P44 (S415-429), recognized by 68% of convalescents, presented IgG and IgA antibody reactivity that positively correlated with nAb titers, suggesting that this is a relevant RBD region and a potential target of IgG/IgA neutralizing activity. DiscussionThis peptide is localized within the area of contact with ACE-2 and harbors the mutation hotspot site K417 present in gamma (K417T), beta (K417N), and omicron (K417N) variants of concern. The epitope profile of vaccinated individuals differed from convalescents, with a more diverse repertoire of immunodominant peptides, recognized by more than 30% of the cohort. Noteworthy, immunodominant regions of recognition by vaccinated coincide with mutation sites at Omicron BA.1, an important variant emerging after massive vaccination. Together, our data show that immune pressure induced by dominant antibody responses may favor hotspot mutation sites and the selection of variants capable of evading humoral response.
  • article 26 Citação(ões) na Scopus
    HSP60: issues and insights on its therapeutic use as an immunoregulatory agent
    (2012) COELHO, Veronica; FARIA, Ana M. C.
    Heat shock proteins 60 (HSP60) is one of the most well studied member of the HSP family. Although found to be a target self antigen in pathological autoimmunity and HSP60-reactive land B cells are part of immune responses in several infectious diseases, there is consistent experimental evidence that HSP60 displays dominant immunoregulatory properties. There are a series of reports on animal models showing that the administration of HSP60 can modulate inflammatory diseases. However, HSP60 has both immune-regulatory and inflammatory properties placing it as an essentially homeostatic antigen, but with potentially harmful effects as well. There have been a series of reports on the successful use of HSP60 and its peptides as immune-modulatory agent for several models of autoimmune diseases and in some clinical trials as well. We believe that the potential risks of HSP60 as a therapeutic agent can be controlled by addressing important factors determining its effects. These factors would be route of administration, appropriate peptides, time point of administration in the course of the disease, and possible association with other modulatory agents.
  • article 4 Citação(ões) na Scopus
    Integrated Metabolic and Inflammatory Signatures Associated with Severity of, Fatality of, and Recovery from COVID-19
    (2023) GARDINASSI, Luiz Gustavo; SERVIAN, Carolina do Prado; LIMA, Gesiane da Silva; ANJOS, Deborah Carolina Carvalho dos; JR, Antonio Roberto Gomes; GUILARDE, Adriana Oliveira; BORGES, Moara Alves Santa Barbara; SANTOS, Gabriel Franco dos; MORAES, Brenda Grazielli Nogueira; SILVA, Joao Marcos Maia; MASSON, Leticia Carrijo; SOUZA, Flavia Pereira de; SILVA, Rodolfo Rodrigues da; ARAUJO, Giovanna Lopes de; RODRIGUES, Marcella Ferreira; SILVA, Lidya Cardozo da; MEIRA, Sueli; FIACCADORI, Fabiola Souza; SOUZA, Menira; ROMAO, Pedro Roosevelt Torres; FERREIRA, Monica Spadafora; COELHO, Veronica; CHAVES, Andrea Rodrigues; SIMAS, Rosineide Costa; VAZ, Boniek Gontijo; FONSECA, Simone Goncalves
    COVID-19 is characterized by diverse clinical outcomes that include asymptomatic to mild manifestations or severe disease and death. Infection by SARS-CoV-2 activates inflammatory and metabolic responses that drive protection or pathology. Severe manifestations of coronavirus disease 2019 (COVID-19) and mortality have been associated with physiological alterations that provide insights into the pathogenesis of the disease. Moreover, factors that drive recovery from COVID-19 can be explored to identify correlates of protection. The cellular metabolism represents a potential target to improve survival upon severe disease, but the associations between the metabolism and the inflammatory response during COVID-19 are not well defined. We analyzed blood laboratorial parameters, cytokines, and metabolomes of 150 individuals with mild to severe disease, of which 33 progressed to a fatal outcome. A subset of 20 individuals was followed up after hospital discharge and recovery from acute disease. We used hierarchical community networks to integrate metabolomics profiles with cytokines and markers of inflammation, coagulation, and tissue damage. Infection by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) promotes significant alterations in the plasma metabolome, whose activity varies according to disease severity and correlates with oxygen saturation. Differential metabolism underlying death was marked by amino acids and related metabolites, such as glutamate, glutamyl-glutamate, and oxoproline, and lipids, including progesterone, phosphocholine, and lysophosphatidylcholines (lysoPCs). Individuals who recovered from severe disease displayed persistent alterations enriched for metabolism of purines and phosphatidylinositol phosphate and glycolysis. Recovery of mild disease was associated with vitamin E metabolism. Data integration shows that the metabolic response is a hub connecting other biological features during disease and recovery. Infection by SARS-CoV-2 induces concerted activity of metabolic and inflammatory responses that depend on disease severity and collectively predict clinical outcomes of COVID-19.IMPORTANCE COVID-19 is characterized by diverse clinical outcomes that include asymptomatic to mild manifestations or severe disease and death. Infection by SARS-CoV-2 activates inflammatory and metabolic responses that drive protection or pathology. How inflammation and metabolism communicate during COVID-19 is not well defined. We used high-resolution mass spectrometry to investigate small biochemical compounds (<1,500 Da) in plasma of individuals with COVID-19 and controls. Age, sex, and comorbidities have a profound effect on the plasma metabolites of individuals with COVID-19, but we identified significant activity of pathways and metabolites related to amino acids, lipids, nucleotides, and vitamins determined by disease severity, survival outcome, and recovery. Furthermore, we identified metabolites associated with acute-phase proteins and coagulation factors, which collectively identify individuals with severe disease or individuals who died of severe COVID-19. Our study suggests that manipulating specific metabolic pathways can be explored to prevent hyperinflammation, organ dysfunction, and death.