VALERIA AOKI
Projetos de Pesquisa
Unidades Organizacionais
Departamento de Dermatologia, Faculdade de Medicina - Docente
LIM/56 - Laboratório de Investigação em Dermatologia e Imunodeficiências, Hospital das Clínicas, Faculdade de Medicina - Líder
LIM/56 - Laboratório de Investigação em Dermatologia e Imunodeficiências, Hospital das Clínicas, Faculdade de Medicina - Líder
14 resultados
Resultados de Busca
Agora exibindo 1 - 10 de 14
- 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.
- Beta-adrenoceptor expression in pemphigus foliaceus(2018) MIYAMOTO, D.; DIAS, A. B. T.; AOKI, V.; BURNIER JR., M. N.
- Increased serum levels of vascular endothelial growth factor in pemphigus foliaceus patients with erythroderma(2017) MIYAMOTO, D.; SOTTO, M. N.; OTANI, C. S. V.; FUKUMORI, L. M. I.; PEREIRA, N. V.; SANTI, C. G.; MARUTA, C. W.; BURNIER, M. N. N.; REBEIS, M. M.; AOKI, V.Background Erythroderma is a clinical skin syndrome shared by patients with cutaneous disorders of distinct aetiologies as a result of the combined actions of chemokines, adhesion molecules, and cytokines, such as vascular endothelial growth factor (VEGF). Objective To evaluate the profile of serum levels of VEGF and soluble vascular endothelial growth factor receptor 1 (sVEGFR-1) in pemphigus foliaceus (PF) patients with erythroderma. Methods We conducted a retrospective study, which included (i) a chart review of all PF patients from the Autoimmune Blistering Clinic, University of Sao Paulo, Brazil, from January 1991 to December 2014, together with an evaluation of demographic variables, hospitalization duration and complications and (ii) analysis of the circulating VEGF and sVEGFR-1 levels in PF patients with erythroderma by ELISA. The controls included patients with pemphigus vulgaris or psoriasis. Results We observed higher serum VEGF levels in PF patients during erythroderma than during the non-erythrodermic phase. PF patients showed increased serum levels of sVEGFR-1 during the erythrodermic phase in comparison to controls. Interestingly, the sVEGFR-1 and antidesmoglein-1 levels were positively correlated during the non-erythrodermic period. Conclusion Erythroderma, which represents one clinical form of PF, implies more severe outcomes. The circulating levels of VEGF, a potent endothelial activator, are increased in PF patients with erythroderma; this result suggests the contribution of the blood vessel endothelium to the pathogenesis of this clinical syndrome. Interestingly, our findings showed a positive correlation between the sVEGFR-1 and antidesmoglein-1 antibody levels, indicating a suppressive response to VEGF augmentation during the erythrodermic phase of PF.
- Characterization of the humoral and insitu autoantibody profile of scalp involvement in pemphigus(2016) MARAGNO, L.; BUSSATO, W. M. M.; MARUTA, C. W.; FUKUMORI, L. M. I.; SOTTO, M. N.; SANTI, C. G.; AOKI, V.
- Atopy patch test with Aleuroglyphus ovatus antigen in patients with atopic dermatitis(2015) LORENZINI, D.; PIRES, M.; AOKI, V.; TAKAOKA, R.; SOUZA, R. L.; VASCONCELLOS, C.BackgroundEpicutaneous test made with dust mite antigens. ObjectiveEvaluation of the response of the epicutaneous test withAleuroglyphus ovatus antigen in atopic patients. MethodsWe patch tested 119 individuals, 48 with atopic dermatitis, 50 with respiratory allergy and 21 healthy controls. We compare the positive response frequency to a closed patch test usingAleuroglyphus ovatusantigen in different concentrations and 48 and 96h reading times among those individuals. ResultsSix patients with atopic dermatitis (12.5%) and 4 with respiratory atopy (8.0%) had positive reactions. None of the non-atopic controls had a positive response. As the antigen concentration raised, the number of positive reactions to epicutaneous test raised as well. ConclusionOur data suggest a positive relation between Atopy Patch Test positive responses andAleuroglyphus ovatusantigen concentration, no matter the kind of the atopic clinical expression.
- Increased expression of in situ IL-31RA and circulating CXCL8 and CCL2 in pemphigus herpetiformis suggests participation of the IL-31 family in the pathogenesis of the disease(2020) MORAIS, K. L.; MIYAMOTO, D.; ORFALI, R. L.; MARUTA, C. W.; SANTI, C. G.; SOTTO, M. N.; SILVA, L. F. F. da; BRANCO, A. C. C. C.; SATO, M. N.; AOKI, VBackground Pemphigus herpetiformis (PH) is a rare clinical subtype of pemphigus with the presence of urticarial plaques, severe pruritus, rare acantholysis and eosinophilic spongiosis. Objectives The aim of this study was to investigate the influence of IL-31 and pro-inflammatory cytokines/chemokines in the pathogenesis of PH. Methods Twenty-five patients with PH and three groups: pemphigus foliaceus (PF = 14), pemphigus vulgaris (PV = 15) and healthy controls (HC = 20) were selected for this study. The groups were analysed by immunohistochemistry utilizing IL-31, IL-31RA, IL-4, IL-17 and TNF-alpha antibodies. Serum levels of IL-4, IL-13, TNF, CXCL8, CCL5 and CCL2 were evaluated by cytometric bead array. Results Analysis of IL-31 family of PH patients revealed the following findings: (i) Enhanced in situ expression of IL-31 in PH samples, compared to PF and to PV (epidermis); (ii) Cutaneous IL-31RA expression in PH samples was higher than in PF, PV and HC groups (epidermis and dermis); (iii) PF patients that evolved to PH showed significant increased IL-31RA epidermal expression during the PH phase. Profile of pro-inflammatory cytokines (IL-4, IL-17 and TNF-alpha) in PH patients' skin exhibited: (i) Enhanced IL-4 expression, when compared to patients with PF (epidermis and dermis) and with PV (epidermis); (ii) Augmented IL-17 expression than PF and PV patients (epidermis); (iii) Augmented expression of TNF-alpha when compared to PF at the epidermal level. Evaluation of circulating cytokines and chemokines showed higher levels of CXCL8 and CCL2 in PH sera compared to HC group. Conclusions IL-31 and IL-31RA, cytokines related to pruritus, and pro-inflammatory chemokines (CXCL8 and CCL2) seem to exert a role in the pathogenesis of PH. These findings support future studies to clarify the role of IL-31 pathway as a potential therapeutic target for patients with PH.
- Deciphering the influence of smoking in adults with atopic dermatitis(2022) AOKI, Valeria; ORFALI, Raquel Leao
- 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.
- Real-world clinical, psychosocial and economic burden of atopic dermatitis: Results from a multicountry study(2024) EYERICH, Kilian; GOODERHAM, Melinda J.; SILVESTRE, Juan Francisco; SHUMACK, Stephen P.; MENDES-BASTOS, Pedro; AOKI, Valeria; ORTONCELLI, Michela; SILVERBERG, Jonathan I.; TEIXEIRA, Henrique D.; CHEN, Shirley H.; CALIMLIM, Brian M.; TAKEMOTO, Shunya; SANCHO, Cristina; FRITZ, Bjoern; IRVINE, Alan D.Background: Atopic dermatitis (AD), a relapsing, inflammatory skin disease, is associated with pruritus that can negatively affect patients' quality of life. Understanding the burden of AD is critical for informing and tailoring treatment and disease management to improve patient outcomes. This study characterized global treatment patterns and the clinical, psychosocial and economic burden of moderate- to-severe AD. Methods: MEASURE- AD was a cross-sectional 28-country study in patients with physician-confirmed moderate- to-severe AD who were either receiving or eligible for systemic therapy for AD. Patients =12 years were enrolled between December 2019 and December 2020 while attending routine office or clinic visit. Primary out-comes included Worst Pruritus Numeric Rating Scale (WP- NRS; range: 0- 10) and Dermatology Life Quality Index (DLQI; range: 0- 30) and Childrens DLQI (CDLQI; range: 0- 30). Secondary outcomes included physician-and patient-reported clinical, psychosocial and economic burden.Results: Of the 1591 patients enrolled, 1558 (1434 adults and 124 adolescents) ful-filled all patient selection criteria and were included in this analysis. Almost all patients (98.4%) in the total population were using AD medications and more than half (56%) were receiving systemic medication (15% systemic monotherapy). The most used systemic therapies were dupilumab (56.3%), systemic glucocorticoids (18.1%) and methotrexate (16.2%). Mean WP- NRS was 5.3 in the total population, and most patients (= 55%) reported moderate- to-severe pruritus (WP-NRS = 4). Mean DLQI was 10.8 and mean CDLQI was 9.6. Secondary endpoints demonstrated substantial clinical, psychosocial, and economic burden of disease. Subgroup analysis demonstrated that patients receiving systemic therapy had lower disease burden than those not taking systemic medications.Conclusions: While systemic therapy lowers overall disease burden, patients with moderate- to-severe AD continue to have substantial multidimensional disease bur-den and uncontrolled disease. Overall, there is a need for effective disease management, including effective treatments that improve patients' psychosocial outcomes and reduce the economic burden of AD.
- Exploring the in situ expression of vascular endothelial growth factor and endoglin in pemphigus foliaceus variants and pemphigus vulgaris(2018) MIYAMOTO, D.; MARUTA, C. W.; SANTI, C. G.; ZOROQUIAIN, P.; DIAS, A. B. T.; MANSURE, J. J.; BURNIER JR., M. N.; AOKI, V.Background Erythroderma is a severe manifestation of pemphigus foliaceus (PF), a blistering disease mediated by IgG autoantibodies against desmoglein 1. Increasing evidence supports the contribution of angiogenic mediators in the pathogenesis of erythroderma. ObjectiveMethodsTo evaluate the in situ expression of vascular endothelial growth factor (VEGF) and endoglin in patients with PF with erythroderma. Formalin-fixed paraffin-embedded skin samples obtained from patients with erythrodermic PF (n = 19; 12 patients with endemic PF), non-erythrodermic PF (n = 17), pemphigus vulgaris (PV; n = 10), psoriasis (n = 10) and healthy individuals (HI; n = 10) were processed in an automated immunohistochemistry platform utilizing anti-VEGF and anti-endoglin as primary antibodies. Reactivity was evaluated both manually (0 = negative; 1+ = mild; 2+ = intense) and through an automated microvessel analysis algorithm. ResultsConclusionVascular endothelial growth factor expression in erythrodermic PF was higher than in non-erythrodermic PF (P = 0.034) and in HI (P = 0.004), and similar to psoriasis (P = 0.667) and PV (P = 0.667). In non-erythrodermic PF, VEGF positivity was similar to HI (P = 0.247), and lower than psoriasis (P = 0.049) and PV (P = 0.049). Both erythrodermic and non-erythrodermic PF presented similar endoglin expression (P = 0.700). In addition, endoglin positivity during erythrodermic PF was similar to psoriasis (P = 0.133) and lower than PV (P = 0.0009). Increased expression of in situVEGF suggests that healing processes are triggered in response to tissue damage led by autoantibodies in PF, especially during erythroderma. Reduced endoglin positivity suggests that an unbalanced angiogenesis may occur during erythrodermic PF. Further studies may help to confirm if the regulation of VEGF and endoglin expression in patients with PF can contribute to control the healing process and enable disease remission. Overexpression of VEGF in erythrodermic PF as well as in PV and psoriasis points out a dysregulated repair process in severe forms of these diseases and suggests VEGF and endoglin could act as prognostic markers and future therapeutic targets to enable proper healing in PF.