SANDRA MARIA MONTEIRO

Índice h a partir de 2011
4
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Unidades Organizacionais
Instituto do Coração, Hospital das Clínicas, Faculdade de Medicina
LIM/19 - Laboratório de Histocompatibilidade e Imunidade Celular, Hospital das Clínicas, Faculdade de Medicina

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  • 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 10 Citação(ões) na Scopus
    Differential microRNA Profile in Operational Tolerance: A Potential Role in Favoring Cell Survival
    (2019) CABRAL, Amanda; CANDIDO, Daran da Silva; MONTEIRO, Sandra Maria; LEMOS, Francine; SAITOVITCH, David; NORONHA, Irene L.; ALVES, Leticia Ferreira; GERAIDO, Murilo Vieira; KALIL, Jorge; CUNHA-NETO, Edecio; FERREIRA, Ludmila Rodrigues Pinto; COEIHO, Veronica
    Background: Operational tolerance (OT) is a state of graft functional stability that occurs after at least 1 year of immunosuppressant withdrawal. MicroRNAs (microRNA) are small non-coding RNAs that downregulate messenger RNA/protein expression of innumerous molecules and are critical for homeostasis. We investigated whether OT in kidney transplantation displays a differential microRNA profile, which would suggest that microRNAs participate in Operational Tolerance mechanisms, and may reveal potential molecular pathways. Methods: We first compared serum microRNA in OT (n = 8) with chronic rejection (CR) (n = 5) and healthy individuals (HI) (n = 5), using a 768-microRNA qPCR-panel. We used the Thermo Fisher Cloud computing platform to compare the levels of microRNAs in the OT group in relation to the other study groups. We performed validation experiments for miR-885-5p, by q-PCR, in a larger number of study subjects (OT = 8, CR = 12, HI = 12), as individual samples. Results: We detected a differential microRNA profile in OT vs. its opposing clinical outcome-CR-suggesting that microRNAs may integrate transplantation tolerance mechanisms. Some miRNAs were detected at higher levels in OT: miR-885-5p, miR-331-3p, miR-27a-5p vs. CR; others, we found at lower levels: miR-1233-3p, miR-572, miR-638, miR-1260a. Considering highly predicted/experimentally demonstrated targets of these miRNAs, bioinformatics analysis revealed that the granzyme B, and death receptor pathways are dominant, suggesting that cell death regulation integrates transplantation tolerance mechanisms. We confirmed higher miR-885-5p levels in OT vs. CR, and vs. HI, in a larger number of subjects. Conclusions: We propose that epigenetics mechanisms involving microRNAs may integrate human transplantation tolerance mechanisms, and regulate key members of the cell death/survival signaling. miR-885-5p could favor cell survival in OT by diminishing the levels of CRADD/RAIDD and CASP3. Nonetheless, given the nature of any complex phenomenon in humans, only cumulative data will help to determine whether this microRNA differential profile may be related to the cause or consequence of operational tolerance.
  • article 1 Citação(ões) na Scopus
    Toward an Integrated View of Operational Tolerance in Human Renal Transplantation: A Systems Biology Perspective
    (2020) COELHO, Veronica; CABRAL, Amanda; MARTINS, Felipe; ARCURI, Helen; CARMONA, Priscila; MORAES-VIEIRA, Pedro Manoel Mendes; LEMOS, Francine; FONSECA, Simone G.; FARIA, Ana Caetano de; MONTEIRO, Sandra Maria; NORONHA, Irene; SAITOVITCH, David; NAKAYA, Helder; FERREIRA, Ludmila Rodrigues Pinto; KALIL, Jorge
    Operational tolerance (OT) is the phenomenon occurring in human renal and liver transplantation in which the body does not reject the organ after discontinuing immunosuppression for at least a year. We revisited the data generated by The Brazilian Multicenter Study on Operational Tolerance involving different conceptual fields- antigen-specific cytokine response, immune cell numbers and repertoire, signaling pathways, and epigenetics. We integrated our data to pave the way to systems biology thinking and harness debate on potential mechanisms in OT. We present original data on systems biology in OT, connecting potential mechanistic players. Using bioinformatics, we identified three dominant features that discriminate OT from its opposing clinical outcome, chronic rejection (CR). The OT-CR discriminative molecules were FOXP3, GATA3 and STAT6, each corresponding to a differential profile: (1) In FOXP3, OT presents preserved regulatory T cell (Treg) numbers but decreased numbers in CR; (2) in GATA3, increased expression is seen in OT; and (3) in STAT6, decreased monocyte activation is seen in OT. With these variables, we built molecular networks to identify interactions related to OT versus CR. Our first systems biology endeavor gave rise to novel potentially relevant interconnected players in OT mechanisms: FOXP3 connecting to interleukin-9 (IL-9) and IL-35 signaling, suggesting their immunoregulatory involvement in OT. Likewise, GATA3/FOXP3 interactions incrementing/stabilizing FOXP3 transcription suggest participation in keeping healthy FOXP3(+). Tregs in OT. We envision that systems biology thinking will greatly contribute to advancing knowledge in human transplantation tolerance in an interactive perspective.