MARIANA COLOMBINI ZANIBONI

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LIM/56 - Laboratório de Investigação em Dermatologia e Imunodeficiências, Hospital das Clínicas, Faculdade de Medicina

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  • article 5 Citação(ões) na Scopus
    Increased expression of Filaggrin and Claudin-1 in the ocular surface of patients with atopic dermatitis
    (2022) CALLOU, T. M. P.; ORFALI, R. L.; SOTTO, M. N.; V, N. Pereira; ZANIBONI, M. C.; AOKI, V; BRITO, M. P.; MATSUDA, M.; SANTO, R. M.
    Background Atopic dermatitis (AD) is an itchy, chronic and inflammatory skin condition, with dysfunctional immune response and skin barrier defects. Reduction of filaggrin (FLG) and tight junctions (TJ) proteins, such as claudin-1 (CLDN-1), expression in cutaneous epithelial barrier is remarkable in AD pathogenesis. Ocular involvement occurs in approximately 40% of AD patients leading to changes in the structure of the conjunctiva. Objectives We aimed to evaluate the expression of FLG and CLDN-1 in the ocular surface of adults with AD, analysing bulbar conjunctival cells collected by a novel non-invasive cellular imprint. Methods Bulbar conjunctival epithelial cells were collected by cellular imprint technique, and FLG and CLDN-1 expression were assessed by immunofluorescence (IF) and real-time polymerase chain reaction (RT-PCR). Results We detected increased expression of FLG and CLDN-1, as well as their transcript levels in AD patients compared with healthy controls (HC). There was a positive correlation between tear film break-up time (TBUT) and FLG expression. Fluorescein staining was inversely associated with FLG expression. Conclusions Our results may reflect a reactive response of the ocular surface to AD-related ocular inflammation and associated dry eye disease. Further investigations focusing on the role of FLG and TJ expression in the ocular surface of AD patients may increment the understanding of the pathophysiology of extracutaneous AD and developing future targeted therapies.
  • article 24 Citação(ões) na Scopus
    Consensus on the therapeutic management of atopic dermatitis Brazilian Society of Dermatology
    (2019) AOKI, Valeria; LORENZINI, Daniel; ORFALI, Raquel Leao; ZANIBONI, Mariana Colombini; OLIVEIRA, Zilda Najjar Prado de; RIVITTI-MACHADO, Maria Cecilia; TAKAOKA, Roberto; WEBER, Magda Blessmann; CESTARI, Tania; GONTIJOS, Bernardo; RAMOSS, Andrea Machado Coelho; SILVA, Claudia Marcia de Resende; CESTARI, Silmara da Costa Pereira; SOUTO-MAYOR, Silvia; CARNEIRO, Francisca Regina; CERQUEIRA, Ana Maria Mosca de; LACZYNSKI, Cristina; PIRES, Mario Cezar
    BACKGROUND: Atopic dermatitis is a highly prevalent inflammatory and pruritic dermatosis with a multifactorial etiology, which includes skin barrier defects, immune dysfunction, and microbiome alterations. Atopic dermatitis is mediated by genetic, environmental, and psychological factors and requires therapeutic management that covers all the aspects of its complex pathogenesis. OBJECTIVES: The aim of this article is to present the experience, opinions, and recommendations of Brazilian dermatology experts regarding the therapeutic management of atopic dermatitis. METHODS: Eighteen experts from 10 university hospitals with experience in atopic dermatitis were appointed by the Brazilian Society of Dermatology to organize a consensus on the therapeutic management of atopic dermatitis. The 18 experts answered an online questionnaire with 14 questions related to the treatment of atopic dermatitis. Afterwards, they analyzed the recent international guidelines on atopic dermatitis of the American Academy of Dermatology, published in 2014, and of the European Academy of Dermatology and Venereology, published in 2018. Consensus was defined as approval by at least 70% of the panel. RESULTS/CONCLUSION: The experts stated that the therapeutic management of atopic dermatitis is based on skin hydration, topical anti-inflammatory agents, avoidance of triggering factors, and educational programs. Systemic therapy, based on immunosuppressive agents, is only indicated for severe refractory disease and after failure of topical therapy. Early detection and treatment of secondary bacterial and viral infections is mandatory, and hospitalization may be needed to control atopic dermatitis flares. Novel target-oriented drugs such as immunobiologicals are invaluable therapeutic agents for atopic dermatitis.
  • article 95 Citação(ões) na Scopus
    Profile of skin barrier proteins (filaggrin, claudins 1 and 4) and Th1/Th2/Th17 cytokines in adults with atopic dermatitis
    (2015) BATISTA, D. I. S.; PEREZ, L.; ORFALI, R. L.; ZANIBONI, M. C.; SAMORANO, L. P.; PEREIRA, N. V.; SOTTO, M. N.; ISHIZAKI, A. S.; OLIVEIRA, L. M. S.; SATO, M. N.; AOKI, V.
    BackgroundAtopic dermatitis (AD) in adults and profile of skin barrier proteins and inflammatory cytokines. ObjectiveEvaluation of the expression of skin barrier proteins such as filaggrin, claudins 1 and 4 and of circulating inflammatory cytokines (Th1/Th2/Th17) in adults with AD. MethodsThirty-three adult patients with AD diagnosed according to the Hanifin & Rajkacriteria, and 25 healthy controls were enrolled in the study. AD severity was measured by Eczema Area and Severity Index (EASI). Laboratory assays included immunohistochemistry analysis of skin barrier proteins, such as filaggrin, claudins 1 and 4 and interleukin-17 (IL-17) from skin samples and determination of circulating cytokine levels (IL-2, 4, 5, 6, 10, 17A, TNF and IFN-) by flow cytometry (Cytometric Bead Array). ResultsWe observed a reduced expression of filaggrin and claudin 1 in lesional skin of AD patients, when compared to controls. There was an inverse correlation of filaggrin expression and disease severity. In addition, IL-17 expression was enhanced in AD patients. Similarly, higher levels of inflammatory cytokines (IL-2, 5, 6, 10, 17A and IFN-) were found in AD patients. ConclusionOur data reinforce the role of an altered skin barrier in the pathogenesis of AD. Our results show not only reduced expression of filaggrin and claudin 1 in lesional atopic skin but also inverse correlation of filaggrin expression and disease severity. Moreover, elevation of in situ IL-17 and of circulating interleukin levels in AD emphasize the systemic, inflammatory profile of this defective skin barrier dermatosis.
  • article 21 Citação(ões) na Scopus
    Atopic dermatitis in adults: clinical and epidemiological considerations
    (2013) ORFALI, Raquel Leao; SHIMIZUA, Marta M.; TAKAOKA, Roberto; ZANIBONI, Mariana C.; ISHIZAKI, Aline S.; COSTA, Anderson A.; TIBA, Ana Paula L.; SATO, Maria Notomi; AOKI, Valeria
    Objective: Atopic dermatitis (AD) is a chronic inflammatory disease causing intense pruritus, and with typical clinical features. There are few epidemiological studies concerning AD in adults, aswell as little information about its prognostic. The aim of this study was to evaluate the clinical and epidemiological course of adults with AD. Methods: 80 patients aged above 18 years (mean age = 29 years) were selected (30 males and 50 females) and interviewed about hospitalization, systemic corticoid usage, age of ADonset, and personal and/or familial history of atopy. Disease severity was evaluated through the Scoring Atopic Dermatitis (SCORAD) tool. Laboratory examination included IgE serum levels and eosinophil blood count. Results: 71 out of 80 patients referred association with respiratory symptoms (18 had asthma, 17 had rhinitis, and 36 had both conditions); nine out of 80 patients denied any respiratory disease. AD patients were divided in mild (n = 25), moderate (n = 30), and severe (n = 25); 56% had one or more hospitalizations due to AD. A positive association was found between IgE serum levels, eosinophil blood count, and disease severity. Conclusion: Adult AD represents a clinical challenge that needs to be better characterized, since it can be misdiagnosed and interferes with the patient's social and personal life. The association of skin and respiratory atopic disease is frequent, and laboratory parameters such as circulating IgE levels and eosinophil blood count may be helpful to assess disease severity.
  • article 28 Citação(ões) na Scopus
    A position paper on the management of itch and pain in atopic dermatitis from the International Society of Atopic Dermatitis (ISAD)/Oriented Patient-Education Network in Dermatology (OPENED) task force
    (2021) MISERY, L.; FORTINA, A. Belloni; HACHEM, M. El; CHERNYSHOV, P.; KOBYLETZKI, L. von; HERATIZADEH, A.; MARCOUX, D.; AOKI, V.; ZANIBONI, M. C.; STALDER, J. -F.; EICHENFIELD, L. F.
    Atopic dermatitis (AD) is a disease that can have a high impact on quality of life, especially due to itch and skin pain. This paper utilizes expertise from members of the International Society of Atopic Dermatitis (ISAD)/Oriented Patient-Education Network in Dermatology (OPENED) task force to review the epidemiology, pathophysiology and exacerbating factors of itch and pain in atopic dermatitis. General principles of treatment are provided, as well as a more detailed evaluation of topical and systemic therapies. Educational and psychological approaches to itch and pain in atopic dermatitis are proposed, along with expert recommendations for the management of itch and pain in atopic dermatitis.
  • article 28 Citação(ões) na Scopus
    Staphylococcus aureus enterotoxins modulate IL-22-secreting cells in adults with atopic dermatitis
    (2018) ORFALI, Raquel Leao; OLIVEIRA, Luanda Mara da Silva; LIMA, Josenilson Feitosa de; CARVALHO, Gabriel Costa de; RAMOS, Yasmim Alefe Leuzzi; PEREIRA, Natalli Zanete; PEREIRA, Naiura Vieira; ZANIBONI, Mariana Colombini; SOTTO, Mirian Nacagami; DUARTE, Alberto Jose da Silva; SATO, Maria Notomi; AOKI, Valeria
    Atopic dermatitis (AD) is a chronic inflammatory immune-mediated skin disease characterized by skin colonization by Staphylococcus aureus. Interleukin (IL)-22, in cooperation with IL-17, triggers antimicrobial peptide elaboration and enhances certain immunological responses. In AD, IL-22 is related to epidermal hyperplasia, keratinocyte apoptosis, and inhibition of antimicrobial peptide (AMP) production. We aimed to evaluate the impact of staphylococcal enterotoxins on the Tc22/Th22 induction in the peripheral blood of AD patients and on CD4(+/)CD8(+)T cells expressing IL-22 in AD skin. Our study showed inhibition of the staphylococcal enterotoxins A and B (SEA and SEB) response by Th22 (CD4(+)IL22(+)IL-17A(-)IFN-gamma(-)) cells in AD patients. In contrast, Tc22 (CD8(+)IL-22(+)IL-17A(-)IFN-gamma(-)) cells were less susceptible to the inhibitory effects of staphylococcal enterotoxins and exhibited an enhanced response to the bacterial stimuli. In AD skin, we detected increased IL-22 transcript expression and T lymphocytes expressing IL-22. Together, our results provide two major findings in response to staphylococcal enterotoxins in adults with AD: dysfunctional CD4(+)IL-22 secreting T cells and increased Tc22 cells. Our hypothesis reinforces the relevance of CD8 T cells modulated by staphylococcal enterotoxins as a potential source of IL-22 in adults with AD, which is relevant for the maintenance of immunological imbalance.
  • article 70 Citação(ões) na Scopus
    Report from the fifth international consensus meeting to harmonize core outcome measures for atopic eczema/dermatitis clinical trials (HOME initiative)
    (2018) CHALMERS, J. R.; THOMAS, K. S.; APFELBACHER, C.; WILLIAMS, H. C.; PRINSEN, C. A.; SPULS, P. I.; SIMPSON, E.; GERBENS, L. A. A.; BOERS, M.; BARBAROT, S.; STALDER, J. F.; ABUABARA, K.; AOKI, V.; ARDELEANU, M.; ARMSTRONG, J.; BANG, B.; BERENTS, T. L.; BURTON, T.; BUTLER, L.; CHUBACHI, T.; CRESSWELL-MELVILLE, A.; DELOZIER, A.; ECKERT, L.; EICHENFIELD, L.; FLOHR, C.; FUTAMURA, M.; GADKARI, A.; GJERDE, E. S.; HALEWIJN, K. F. van; HAWKES, C.; HOWELLS, L.; HOWIE, L.; HUMPHREYS, R.; ISHII, H. A.; KATAOKA, Y.; KATAYAMA, I.; KOUWENHOVEN, W.; LANGAN, S. M.; LESHEM, Y. A.; MERHAND, S.; MINA-OSORIO, P.; MUROTA, H.; NAKAHARA, T.; NUNES, F. P.; NYGAARD, U.; NYGARDAS, M.; OHYA, Y.; ONO, E.; REHBINDER, E.; ROGERS, N. K.; ROMEIJN, G. L. E.; SCHUTTELAAR, M. L. A.; SEARS, A. V.; SIMPSON, M. A.; SINGH, J. A.; SROUR, J.; STUART, B.; SVENSSON, A.; TALMO, G.; TALMO, H.; TEIXEIRA, H. D.; THYSSEN, J. P.; TODD, G.; TORCHET, F.; VOLKE, A.; KOBYLETZKI, L. von; WEISSHAAR, E.; WOLLENBERG, A.; ZANIBONI, M.
    This is the report from the fifth meeting of the Harmonising Outcome Measures for Eczema initiative (HOME V). The meeting was held on 12-14 June 2017 in Nantes, France, with 81 participants. The main aims of the meeting were (i) to achieve consensus over the definition of the core domain of long-term control and how to measure it and (ii) to prioritize future areas of research for the measurement of the core domain of quality of life (QoL) in children. Moderated whole-group and small-group consensus discussions were informed by presentations of qualitative studies, systematic reviews and validation studies. Small-group allocations were performed a priori to ensure that each group included different stakeholders from a variety of geographical regions. Anonymous whole-group voting was carried out using handheld electronic voting pads according to pre-defined consensus rules. It was agreed by consensus that the long-term control domain should include signs, symptoms, quality of life and a patient global instrument. The group agreed that itch intensity should be measured when assessing long-term control of eczema in addition to the frequency of itch captured by the symptoms domain. There was no recommendation of an instrument for the core outcome domain of quality of life in children, but existing instruments were assessed for face validity and feasibility, and future work that will facilitate the recommendation of an instrument was agreed upon.
  • article 7 Citação(ões) na Scopus
    Up-regulation of HMGB1 and TLR4 in skin lesions of lichen planus
    (2018) CARVALHO, Gabriel Costa de; HIRATA, Fabiana Yasumoto Araujo; DOMINGUES, Rosana; FIGUEIREDO, Cristina Adelaide; ZANIBONI, Mariana Colombini; PEREIRA, Naiura Vieira; SOTTO, Mirian Nacagami; AOKI, Valeria; DUARTE, Alberto Jose da Silva; SATO, Maria Notomi
    Lichen planus (LP) is a chronic, mucocutaneous inflammatory disease of an unknown aetiology. The disease has been associated with certain viruses, and the factors such as DAMPs (damage-associated molecular patterns) and PAMPs (pathogen-associated molecular patterns) may also contribute to the inflammatory response in LP. HMGB1 (high mobility group box 1 protein) is one of the major DAMPs that induces inflammation and could trigger LP disease. The present study was aimed to examine TLR4, RAGE and HMGB1 production in epidermis or dermis by immunohistochemistry and the respective expression of these targets in the skin lesions of patients with LP. Moreover, we measured HMGB1 serum levels by ELISA. The results showed similar profile of expression by HMGB1 and TLR4, which are decreased at epidermis and up-regulated at dermis of skin lesions of LP patients that was sustained by intense cellular infiltration. RAGE expression was also increased in dermis of LP. Although there is increased RAGE protein levels, a decreased RAGE transcript levels was detected. Similar HMGB1 serum levels were detected in the LP and control groups. This study demonstrates that HMGB1 and TLR4 could contribute to the inflammatory LP process in skin.
  • article 1 Citação(ões) na Scopus
    Consensus on the therapeutic management of atopic dermatitis - Brazilian Society of Dermatology: an update on phototherapy and systemic therapy using e-Delphi technique
    (2023) ORFALI, Raquel Leao; LORENZINI, Daniel; BRESSAN, Aline; TANAKA, Anber Ancel; CERQUEIRA, Ana Maria Mosca de; HIRAYAMA, Andre da Silva; RAMOS, Andrea Machado Coelho; PROENCA, Carolina Contin; SILVA, Claudia Marcia de Resende; LACZYNSKI, Cristina Marta Maria; CARNEIRO, Francisca Regina; DUARTE, Gleison; HANS FILHO, Gunter; GONCALVES, Heitor de Sa; MELO, Ligia Pessoa de; AZULAY-ABULAFIA, Luna; WEBER, Magda Blessmann; RIVITTI-MACHADO, Maria Cecilia; ZANIBONI, Mariana Colombini; OGAWA, Marilia; PIRES, Mario Cezar; IANHEZ, Mayra; FELIX, Paulo Antonio Oldani; BONAMIGO, Renan; TAKAOKA, Roberto; LAZZARINI, Rosana; CESTARI, Silmara; MAYOR, Silvia Assumpcao Soutto; CESTARI, Tania; OLIVEIRA, Zilda Najjar Prado de; SPULS, Phyllis I.; GERBENS, Louise A. A.; AOKI, Valeria
    This publication is an update of the ""Consensus on the therapeutic management of atopic dermatitis - Brazilian Society of Dermatology"" published in 2019, considering the novel, targeted-oriented systemic therapies for atopic dermatitis. The initial recommendations of the current consensus for systemic treatment of patients with atopic dermatitis were based on a recent review of scientific published data and a consensus was reached after voting. The Brazilian Society of Dermatology invited 31 experts from all regions of Brazil and 2 international experts on atopic dermatitis who fully contributed to the process. The methods included an e-Delphi study to avoid bias, a literature search and a final consensus meeting. The authors added novel approved drugs in Brazil and the indication for phototherapy and systemic therapy for AD. The therapeutical response to systemic treatment is hereby reported in a suitable form for clinical practice and is also part of this updated manuscript. (c) 2023 Sociedade Brasileira de Dermatologia.