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
160 resultados
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- Update on fogo selvagem, an endemic form of pemphigus foliaceus(2015) AOKI, Valeria; RIVITTI, Evandro A.; DIAZ, Luis A.Pemphigus are organ-specific autoimmune diseases, where autoantibodies (mainly immunoglobulin [Ig]G) directed against epidermal targets (glycoproteins of the desmosomal core) are detected. Endemic pemphigus foliaceus or fogo selvagem (FS) is one of the variants of pemphigus foliaceus pemphigus foliaceus that shares the same clinical and immunopathological features of the classic non-endemic pemphigus foliaceus form, including pathogenic IgG (mainly IgG4) autoantibodies directed against the ectodomain of desmoglein 1 (Dsg1), that lead to acantholysis. Pathogenesis of FS is complex, involving genetic, environmental and immunological factors. Human leukocyte antigen (HLA)-DRB1 alleles DRB1*0404, *1402, *1406 or *0102 have been previously identified as risk factors for FS (relative risk, >14). Individuals exposed to hematophagous insects are more susceptible to develop the disease. Non-pathogenic anti-Dsg1 antibodies of the IgG1 subclass, directed against the extracellular 5 domain of Dsg1, are detected in patients in the preclinical stage of the disease, and also in healthy controls living in endemic areas. In counterpart, patients with FS show pathogenic anti-Dsg1 IgG4 autoantibodies that bind the pathogenic extracellular 1 and 2 domains of Dsg1, emphasizing the intramolecular epitope-spreading hypothesis. A possible explanation for the development of the autoimmune process would be antigenic mimicry, initiated by environmental stimuli in those genetically predisposed individuals. Characterization of the pathogenesis of FS will allow the development of specific therapeutic targets, and the elucidation of other autoimmune processes.
- Pyostomatitis vegetans and its relation to inflammatory bowel disease, pyoderma gangrenosum, pyodermatitis vegetans, and pemphigus(2012) NICO, Marcello M. S.; HUSSEIN, Thais P.; AOKI, Valeria; LOURENCO, Silvia V.J Oral Pathol Med (2012) 41: 584588 Pyostomatitis vegetans (PSV) is an intraoral pustular eruption considered by most authors to represent the mucous analogous of cutaneous pyoderma gangrenosum and its vegetating presentations (pyodermatitis vegetans). A strong correlation of PSV with inflammatory bowel disease (IBD) is well documented. The histopathology of PSV lesions usually reveals acanthosis, and neutrophils and/or eosinophils infiltration with intraepithelial or subepithelial abscesses; acantholysis is present in some cases. We studied four patients with IBD that presented oral lesions suggestive of PSV. Two male and two female patients were included. The histopathology of oral lesions of two patients revealed findings typical for PSV. The other two patients showed findings typical for pemphigus vulgaris (PV), although the course of their symptoms paralleled that of the bowel disease. Our findings may suggest that pustular lesions in patients with IBD can be a presentation of both PSV and PV; adequate diagnosis is required because clinical presentation is very similar.
- Analysis of the reactivity of indirect immunofluorescence in patients with pemphigus foliaceus and pemphigus vulgaris using rat bladder epithelium as a substrate(2011) ORTOLAN, Damaris G.; SOUZA, Danielle P. G.; AOKI, Valeria; SANTI, Claudia G.; GABBI, Tatiana V. B.; ICHIMURA, Ligia M. F.; MARUTA, Celina W.OBJECTIVES: To evaluate the reactivity of indirect immunofluorescence using rat bladder epithelium as a substrate in patients with pemphigus foliaceus and pemphigus vulgaris from the Department of Dermatology, University of Sao Paulo Medical School, Brazil. METHODS: Thirty-two patients (8 male and 24 female) from the Department of Dermatology, University of Sao Paulo Medical School, were selected. Three had mucosal pemphigus vulgaris, 20 had mucocutaneous pemphigus vulgaris, and 9 had pemphigus foliaceus. Patients' sera were tested by indirect immunofluorescence performed on human foreskin and rat bladder epithelium and by ELISA assays utilizing baculovirus-expressed recombinant desmoglein 3 and desmoglein 1. RESULTS: No patients with mucosal pemphigus vulgaris, 5 of 20 patients with mucocutaneous pemphigus vulgaris (25%) and 4 of 9 patients with pemphigus foliaceus (44%) had positive indirect immunofluorescence using rat bladder epithelium as a substrate. CONCLUSION: Indirect immunofluorescence using rat bladder epithelium as a substrate is recommended whenever a diagnosis of paraneoplastic pemphigus is considered. The identification of a subset of pemphigus foliaceus and pemphigus vulgaris patients that recognizes desmoplakins by this laboratory tool is critical to avoid the misdiagnosis of paraneoplastic pemphigus.
- Evidence of regulatory myeloid dendritic cells and circulating inflammatory epidermal dendritic cells-like modulated by Toll-like receptors 2 and 7/8 in adults with atopic dermatitis(2017) SANTOS, Vanessa G. dos; ORFALI, Raquel L.; TITZ, Tiago de Oliveira; DUARTE, Alberto J. da Silva; SATO, Maria N.; AOKI, ValeriaBackgroud Atopic dermatitis (AD) is a chronic, inflammatory skin disease characterized by intense pruritus and xerosis. Dendritic cells (DC) play an essential role in tissue inflammation in atopic dermatitis (AD) skin, especially the inflammatory epidermal dendritic cells (IDEC), a particular subset of myeloid dendritic cells (mDC). The aim of the present study was to assess the phenotype and function of mDC and circulating IDEC-like in peripheral blood mononuclear cells (PBMC) of adults with AD. Methods We selected 21 AD patients and 21 non-AD controls, age and gender matched. Expressions of Fc epsilon RI, CD36, TNF, IFN-gamma , and IL-10 in mDC were analyzed by flow cytometry under various stimuli, such as staphylococcal enterotoxin B (SEB), TLR2 (Pam3CSK4), TLR4 (LPS), and TLR7/8 (CL097) agonists. Results The most prominent findings in AD patients were: (i) enhanced frequency of IL-10 under TLR4 (LPS), and decreased frequency of IFN-gamma and TNF under TLR2 (Pam3CSK4) and 7/8 (CL097) stimulation in classic mDC; (ii) elevation of circulating IDEC-like frequency with TLR2 (Pam3CSK4) stimuli, augmented frequency of IFN-gamma in nonstimulated condition, and of IL-10 under TLR7/8 (CL097) stimuli in IDEC-like population. Conclusions In AD individuals, classic mDC showed an immunomodulatory profile, favoring tolerance in a combined action with IDEC-like, and inducing Th1 polarization. Our findings indicate a potential role of IDEC-like in the maintenance of inflammation in atopic dermatitis patients; moreover, IDEC-like may exert a regulatory impact on T cells of AD individuals through IL-10, often induced by agonist mimicking single stranded RNA virus.
article Correlation between Histopathological Findings and Results of Direct Immunofluorescence in the Diagnosis of Canine Localized Cutaneous Chronic Lupus Erythematosus(2017) ODAGUIRI, Juliana; AOKI, Valeria; FUKUMORI, Ligia Maria Ichimura; PERIGO, Alexandre Marques; MICHALANY, Nilceo Scwery; FONTANA, Isabella; LARSSON, Carlos EduardoBackground: Localized chronic cutaneous lupus erythematosus (CCLE), also known as discoid lupus erythematosus, is one of the most prevalent canine autoimmune skin diseases. Histopathology is considered the gold standard for the diagnosis of CCLE and the accuracy of which can be increased by use of direct immunofluorescence (DIF). This study aimed to investigate the fluorescence pattern revealed by DIF in cases of canine localized CCLE and to establish and compare its effectiveness with that obtained from histopathology. Materials, Methods & Results: Eleven dogs suspicious to localized CCLE, i.e., those animals that presented mucocutaneous lesions as erythema, leucoderma, erosive-ulcerative lesions, and loss of nasal planum architecture and its transition to the haired skin underwent medical physical and laboratory examinations (blood count, platelet count, determination of alanine transaminase, alkaline phosphatase, total protein, serum albumin, urea, creatinine). Only those animals that proved to be normal across both the physical and laboratorial evaluation were included in Group I. Animals belonging to this group were submitted to general anesthesia to biopsy two samples of lesioned skin from nasal planum to histopathologic examination and DIF test. Five dogs with no skin lesions were included in Group II as negative control to the DIF assay. Two samples of no lesioned skin from nasal planum were biopsied to histopathologic and DIF evaluation. The kappa (k) coefficient was used to determine the degree of agreement and reliability of the results of both tests. A P-value < 5% was considered to be statistically significant. In Group I, all animals were normal across both the physical and laboratorial evaluation. A diagnosis of canine CCLE was established in 81.8% (9/11) of the animals based on histopathology analysis. Two dogs, numbers 10 and 11, respectively, had histopathologic findings suggestive of cutaneous leishmaniasis and compatible with canine demodicosis. The DIF assay confirmed the diagnostic of canine CCLE in 100% (11/11) of the cases, including dogs numbers 10 and 11. Direct immunofluorescence positivity for canine localized CCLE was determined by the presence of homogeneous green fluorescence in the basement membrane zone, with IgM and C3 immunoreagents being found at a significantly higher frequency (P = 0.007) than IgA and IgG (P = 0.017 and P = 0.037, respectively). In Group II, no alterations from histopathologic examination and unspecific fluorescence from DIF reaction were shown in all animals belonging to this group. A substantial and significant degree of agreement or reliability (k = 0.738 and P = 0.002, respectively) was established between the results of both tests. Discussion: In veterinary medicine, there is a lack of studies about DIF around autoimmune dermatoses. This is the first manuscript comparing histopathological and direct immunofluorescence findings in the diagnostic of dogs with localized CCLE. In the present study, the positivity to the DIF assay for canine localized CCLE was established by the presence of green fluorescence of a homogeneous morphologic pattern, especially for IgM and C3, located in the BMZ and cutaneous annexes. Direct immunofluorescence excluded the suspicion of cutaneous leishmaniasis determined by the histopathological findings and confirmed the diagnostic of canine localized CCLE in the dog number 10. Statistically, a substantial degree of agreement and reliability was shown between DIF and histopathology. Therefore, we concluded that the DIF assay is a highly effective and useful complementary examination that improves our ability to diagnose canine CCLE.conferenceObject Anti-Desmoglein 1 autoantibodies from Fogo Selvagem recognize LJM11, a member of the ""yellow"" family of salivary proteins from Lutzomyia longipalpis(2012) QIAN, Y.; JEONG, J. S.; MALDONADO, M.; EVANGELISTA, F.; QAQISH, B. F.; AOKI, V.; HANS-FILHIO, G.; RIVITTI, E. A.; VALENZUELA, J. G.; DIAZ, L. A.- Laryngeal involvement in pemphigus vulgaris: a proposed classification(2012) MAHMOUD, A.; MIZIARA, I. D.; COSTA, K. C.; SANTI, C. G.; MARUTA, C. W.; AOKI, V.Objective: (1) To investigate the incidence of laryngeal involvement in a large series of patients with pemphigus vulgaris, using endoscopic examination, (2) to describe the lesions, and (3) to establish a classification of laryngeal involvement in pemphigus vulgaris based on the location of the lesions. Study design: Prospective study. Methods: A total of 40 sequentially treated pemphigus vulgaris patients, diagnosed using clinical, histological and immunofluorescence criteria, were evaluated for laryngeal manifestations using endoscopic examination. The results were used to establish a graded classification of laryngeal involvement according to the location of the lesions. Results: Active laryngeal lesions (ulcers or blisters) were found in 16 patients (40 per cent). Of these, 37.5 per cent were classified as grade I, 20 per cent as grade II, 20 per cent as grade III and 17.5 per cent as grade IV. Conclusion: Laryngeal involvement is common in pemphigus vulgaris and must be considered at the point of diagnosis. Grade I lesions are the most frequent.
- Bullous pemphigoid(2019) MIYAMOTO, Denise; SANTI, Claudia Giuli; AOKI, Valeria; MARUTA, Celina WakisakaBullous pemphigoid is the most frequent autoimmune bullous disease and mainly affects elderly individuals. Increase in incidence rates in the past decades has been attributed to population aging, drug-induced cases and improvement in the diagnosis of the nonbullous presentations of the disease. A dysregulated T cell immune response and synthesis of IgG and IgE autoantibodies against hemidesmosomal proteins (BP180 and BP230) lead to neutrophil chemotaxis and degradation of the basement membrane zone. Bullous pemphigoid classically manifests with tense blisters over urticarial plaques on the trunk and extremities accompanied by intense pruritus. Mucosal involvement is rarely reported. Diagnosis relies on (1) the histopathological evaluation demonstrating eosinophilic spongiosis or a subepidermal detachment with eosinophils; (2) the detection of IgG and/or C3 deposition at the basement membrane zone using direct or indirect immunofluorescence assays; and (3) quantification of circulating autoantibodies against BP180 and/or BP230 using ELISA. Bullous pemphigoid is often associated with multiple comorbidities in elderly individuals, especially neurological disorders and increased thrombotic risk, reaching a 1-year mortality rate of 23%. Treatment has to be tailored according to the patient's clinical conditions and disease severity. High potency topical steroids and systemic steroids are the current mainstay of therapy. Recent randomized controlled studies have demonstrated the benefit and safety of adjuvant treatment with doxycycline, dapsone and immunosuppressants aiming a reduction in the cumulative steroid dose and mortality.
- Direct immunofluorescence findings and thrombophilic factors in livedoid vasculopathy: how do they correlate?(2014) CRIADO, P. R.; GIACOMO, T. H. B. Di; SOUZA, D. P. G.; SANTOS, D. V.; AOKI, V.
conferenceObject Characterization of haematological and transaminase laboratory findings associated with upadacitinib use in moderate-to-severe atopic dermatitis: results of two phase III Trials (Measure Up 1 and 2)(2022) SILVERBERG, J. I.; GOODERHAM, M. J.; BRUIN-WELLER, M. S. de; PAPP, K. A.; AOKI, V.; PALLER, A. S.; OFORI, S.; TENORIO, A. R.; LIU, Y.; LIU, J.; CHOVATIYA, Raj