MIRIAN NACAGAMI SOTTO
Projetos de Pesquisa
Unidades Organizacionais
Departamento de Patologia, Faculdade de Medicina - Docente
LIM/53 - Laboratório de Micologia, Hospital das Clínicas, Faculdade de Medicina
LIM/53 - Laboratório de Micologia, Hospital das Clínicas, Faculdade de Medicina
10 resultados
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- Analysis of microvasculature phenotype and endothelial activation markers in skin lesions of lacaziosis (Lobomycosis)(2015) QUARESMA, Juarez A. S.; BRITO, Maysa V.; SOUSA, Jorge R.; SILVA, Luciana M.; HIRAI, Kelly E.; ARAUJO, Rafael S.; BRITO, Arival C. de; CARNEIRO, Francisca R. O.; FUZII, Hellen T.; PAGLIARI, Carla; SOTTO, Mirian N.; DUARTE, Maria I. S.Jorge Lobo's disease is a rare mycosis characterized by chronic inflammation, which causes skin lesions in the absence of visceral dissemination. The disease occurs mainly in hot and humid climates and most cases have been registered in the Brazilian Amazon region. This study investigated possible microvascular alterations in skin lesions caused by infection with Lacazia loboi which may interfere with the clinical progression of the disease. Immunohistochemistry was used to evaluate the density of blood and lymphatic vessels, as well as expression of the cell adhesion molecules ICAM-1, VCAM-1 and E-selectin. The results showed a reduced number of blood (62.66 +/- 20.30 vessels/mm(2)) and lymphatic vessels (3.55 +/- 5.84 vessels/mm(2)) in Jorge Lobo's disease when compared to control skin (169.66 +/- 66.38 blood vessels/mm(2) and 8 +/- 2.17 lymphatic vessels/mm(2)). There were a larger number of vessels expressing ICAM-1 (27.58 +/- 15.32 vessels/mm(2)) and VCAM-1 (7.55 +/- 6.2 vessels/mm(2)). No difference was observed in the expression of E-selectin (4.66 +/- 11 vessels/mm(2)). Taken together, the results indicate changes in the local microvasculature which may interfere with the development of an efficient cell-mediated immune response and may explain restriction of the fungus to the site of injury.
- Increased corticotropin-releasing hormone (CRH) expression in cutaneous lupus lesions(2015) SCHMITZ, M. K.; BOTTE, D. A.; SOTTO, M. N.; BORBA, E. F.; BONFA, E.; MELLO, S. B. V. deObjective Corticotropin-releasing hormone (CRH) and pro-opiomelanocortin (POMC) axis activation leads to the production of hormones, such as adrenocorticotrophic hormone (ACTH) and the -melanocyte stimulating hormone (-MSH). Data regarding the role of these hormones in systemic lupus erythematosus (SLE) are scarce. In the present study we aim to evaluate the participation of this axis in the cutaneous involvement of SLE. Methods Seventeen SLE patients were clinically evaluated, and biopsies from affected and unaffected skin of these patients were compared with 17 healthy control individuals. Immunohistochemical analyses for CRH, ACTH, -MSH, and MC-1R were performed, and the serum levels of -MSH, IL-1, IL-1ra, IL-6, IL-10, IL-12p70, IL-17, TNF-, and IFN- were measured. Results The affected skin of the SLE patients exhibited higher CRH expression in the deep dermis compared to the skin of the controls (p=0.024), whereas the tissue expression of ACTH, cortisol, -MSH and its receptor MC-1R were comparable in SLE patients and controls. Higher serum levels of IFN- (p=0.041), TNF- (p=0.001) and IL-6 (p=0.049) were observed in SLE patients compared with controls, while -MSH levels were similar in both groups. Conclusion The novel finding of elevated CRH expression solely in the affected skin deep dermis supports the notion of a cutaneous local dysfunction of the CRH-POMC axis in the pathogenesis of cutaneous SLE lesions.
- Post-kala-azar dermal leishmaniasis and leprosy: case report and literature review(2015) TRINDADE, Maria Angela Bianconcini; SILVA, Lana Luiza da Cruz; BRAZ, Lucia Maria Almeida; AMATO, Valdir Sabbaga; NAAFS, Bernard; SOTTO, Mirian NacagamiBackground: Post-kala-azar dermal leishmaniasis (PKDL) is a dermal complication of visceral leishmaniasis (VL), which may occur after or during treatment. It has been frequently reported from India and the Sudan, but its occurrence in South America has been rarely reported. It may mimic leprosy and its differentiation may be difficult, since both diseases may show hypo-pigmented macular lesions as clinical presentation and neural involvement in histopathological investigations. The co-infection of leprosy and VL has been reported in countries where both diseases are endemic. The authors report a co-infection case of leprosy and VL, which evolved into PKDL and discuss the clinical and the pathological aspects in the patient and review the literature on this disease. Case presentation: We report an unusual case of a 53-year-old female patient from Alagoas, Brazil. She presented with leprosy and a necrotizing erythema nodosum, a type II leprosy reaction, about 3 month after finishing the treatment (MDT-MB) for leprosy. She was hospitalized and VL was diagnosed at that time and she was successfully treated with liposomal amphotericin B. After 6 months, she developed a few hypo-pigmented papules on her forehead. A granulomatous inflammatory infiltrate throughout the dermis was observed at histopathological examination of the skin biopsy. It consisted of epithelioid histiocytes, lymphocytes and plasma cells with the presence of amastigotes of Leishmania in macrophages (Leishman's bodies). The diagnosis of post-kala-azar dermal leishmaniasis was established because at this time there was no hepatosplenomegaly and the bone marrow did not show Leishmania parasites thus excluding VL. About 2 years after the treatment of PKDL with liposomal amphotericin B the patient is still without PKDL lesions. Conclusion: Post-kala-azar dermal leishmaniasis is a rare dermal complication of VL that mimics leprosy and should be considered particularly in countries where both diseases are endemic. A co-infection must be seriously considered, especially in patients who are non-responsive to treatment or develop persistent leprosy reactions as those encountered in the patient reported here.
- Jorge Lobo's Disease: Immunohistochemical Characterization of Dendritic Cells in Cutaneous Lesions(2015) BARBOZA, Tania Cristina; QUARESMA, Juarez Antonio Simoes; BRITO, Arival Cardoso de; XAVIER, Marilia Brasil; OLIVEIRA, Clivia Maria Moraes de; UNGER, Deborah Aben Athar; DUARTE, Maria Irma Seixas; SOTTO, Mirian Nacagami; PAGLIARI, CarlaJorge Lobo's disease (JLD) is a cutaneous chronic mycosis caused by Lacazia loboi. We studied Factor XIIIa + dermal dendrocytes (FXIIIa + DD), Langerhans cells (LC) through the expression of langerin and the expression of S100 protein. A total of 41 biopsies and 10 normal skins (control) were developed with a polymer-based immunohistochemical method. Lesions presented infiltrate comprising macrophages, some asteroid corpuscles, lymphocytes, multinucleated giant cells and a large number of fungi. LCs presented short dendrites and were scarcely distributed. Dermal langerin + cells were detected in nine JLD lesions. FXIIIa + DD were hypertrophic, visualized in the inflammatory infiltrate of JLD lesions. Cells S100+ were present in JLD and control group with a similar number of cells. A total of 14 specimens did not express FXIIIa, and this considerable number probably contributed to the statistical similarity with the control group. The results indicate that LCs are present in the immune response against Lacazia loboi. Some dermal langerin + cells could be another subset of dendritic cells. Our data indicate changes of LCs in JLD cutaneous lesions and present, for the first time, results that show langerin + cells in the dermis and corroborate previous observations on the participation of FXIIIa + DD in the in situ immune response in JLD.
- 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.
- Evaluation of the 2008 World Health Organization classification for non-mycosis fungoides, non-Sezary syndrome T/NK-cell lymphomas with primary cutaneous involvement(2015) CHANG, Daniel; ZERBINI, Maria Claudia Nogueira; SOTTO, Mirian Nacagami; SIQUEIRA, Sheila Aparecida Coelho; SANCHES, Jose AntonioBackgroun: Cutaneous non-mycosis fungoides non-Sezary syndrome T/NK cell lymphomas (non-MF/non-SS CTCL) are rare. In 2005, a consensus of the World Health Organization (WHO) and European Organization for Research and Treatment of Cancer (EORTC) classifications for primary cutaneous lymphomas was established. These guidelines were then adopted into the WHO Classification of Tumours of Haematopoietic and Lymphoid Tissues, 2008. This study aims to assess the applicability of the WHO 2008 classification in a retrospective series of CTCL cases registered in a reference academic center in Brazil. Methods: Twenty-seven patients with non-MF/non-SS CTCL were studied. Clinical, histopathological and immunophenotypical features based on an extensive panel of antibodies were applied to classify the cases according to the WHO, 2008. Results: Overall, diagnostic categories included eight (29.6%) cutaneous anaplastic large-cell lymphoma, five (18.5%) lymphomatoid papulosis, six (22.2%) extranodal natural killer (NK)/T-cell lymphoma, nasal type, five (18.5%) adult T-cell leukemia/lymphoma, one (3.7%) cutaneous CD8-positive aggressive epidermotropic cytotoxic T-cell lymphoma and two (7.4%) of peripheral T-cell lymphoma not otherwise specified (NOS). Conclusions: The WHO classification (2008) was applicable to most cases of non-MF/non-SS CTCL, while some cases remained unclassified and were considered NOS-peripheral T-cell lymphoma. An unexpected high frequency of NK/T-cell lymphoma nasal type was observed.
- Unusual remodeling of the hyalinization band in vulval lichen sclerosus by type V collagen and ECM 1 protein(2015) GODOY, Charles A.P.; TEODORO, Walcy R.; VELOSA, Ana Paula P.; GARIPPO, Ana Lucia; EHER, Esmeralda Miristeni; PARRA, Edwin Roger; SOTTO, Mirian N.; CAPELOZZI, Vera L.OBJECTIVES: The vulva is the primary site affected in lichen sclerosus, a chronic dermatosis in women that is histologically characterized by a zone of collagen remodeling in the superior dermis. The normal physiological properties of the vulva depend on the assembly of collagen types I (COLI), III (COLIII) and V (COLV), which form heterotypic fibers, and extracellular matrix protein interactions. COLV regulates the heterotypic fiber diameter, and the preservation of its properties is important for maintaining normal tissue architecture and function. In the current work, we analyzed the expression of COLV and its relationship with COLI, COLIII, elastic fibers and extracellular matrix protein 1 in vulvar biopsies from patients with lichen sclerosus. METHODS: Skin biopsies from 21 patients with lichen sclerosus, classified according to Hewitt histological criteria, were studied and compared to clinically normal vulvar tissue (N=21). Morphology, immunohistochemistry, immunofluorescence, 3D reconstruction and morphometric analysis of COLI, COLIII, COLV deposition, elastic fibers and extracellular matrix 1 expression in a zone of collagen remodeling in the superior dermis were performed. RESULTS: A significant decrease of elastic fibers and extracellular matrix 1 protein was present in the hyalinization zone of lichen sclerosus compared to healthy controls. The non-homogeneous distribution of collagen fibers visualized under immunofluorescence in the hyalinization zone of lichen sclerosus and control skin was confirmed by histomorphometry. Lichen sclerosus dermis shows a significant increase of COLI, COLIII and COLV expression compared to the healthy controls. Significant inverse associations were found between elastic fibers and COLV and between COLV and extracellular matrix 1 expression. A direct association was found between elastic fiber content and extracellular matrix 1 expression. Tridimensional reconstruction of the heterotypic fibers of the lichen sclerosus zone of collagen remodeling confirmed the presence of densely clustered COLV. CONCLUSIONS: Increased deposition of abnormal COLV and its correlation with extracellular matrix 1 and elastic fibers suggest that COLV may be a trigger in the pathogenesis of lichen sclerosus.
- TOLL-LIKE RECEPTORS (TLR) 2 AND 4 EXPRESSION OF KERATINOCYTES FROM PATIENTS WITH LOCALIZED AND DISSEMINATED DERMATOPHYTOSIS(2015) OLIVEIRA, Cristiane Beatriz de; VASCONCELLOS, Cidia; SAKAI-VALENTE, Neusa Y.; SOTTO, Mirian Nacagami; LUIZ, Fernanda Guedes; BELDA JUNIOR, Walter; SOUSA, Maria da Gloria Teixeira de; BENARD, Gil; CRIADO, Paulo RicardoThere are few studies on the role of innate immune response in dermatophytosis. An investigation was conducted to define the involvement of Toll-Like Receptors (TLRs) 2 and 4 in localized (LD) and disseminated (DD) dermatophytosis due to T. rubrum. Fifteen newly diagnosed patients, eight patients with LD and seven with DD, defined by involvement of at least three body segments were used in this study. Controls comprised twenty skin samples from healthy individuals undergoing plastic surgery. TLR2 and TLR4 were quantified in skin lesions by immunohistochemistry. A reduced expression of TLR4 in the lower and upper epidermis of both LD and DD patients was found compared to controls; TLR2 expression was preserved in the upper and lower epidermis of all three groups. As TLR4 signaling induces the production of inflammatory cytokines and neutrophils recruitment, its reduced expression likely contributed to the lack of resolution of the infection and the consequent chronic nature of the dermatophytosis. As TLR2 expression acts to limit the inflammatory process and preserves the epidermal structure, its preserved expression may also contribute to the persistent infection and limited inflammation that are characteristic of dermatophytic infections.
- Lipoprotein(a) and livedoid vasculopathy: A new thrombophilic factor?(2015) CRIADO, P. R.; ESPINELL, D. P. S.; BARRETO, P.; GIACOMO, T. H. B. Di; SOTTO, M. N.Livedoid vasculopathy is a chronic disorder characterised by recurrent reticulated purpura on lower extremities, associated with painful purpuric or necrotic macules and ulcerations. Current knowledge indicates LV to be a thrombo-occlusive vasculopathy of cutaneous blood vessels; exact pathogenesis is yet to be understood. Elevated levels of lipoprotein(a) have been found in LV patients. To date, elevated plasma levels of lipoprotein(a) are considered an independent and causal genetic risk factor for the development of cardiovascular disease, as well as a relevant factor in hypercoagulable states. Because of its structural homology with plasminogen, Lp(a) might have important anti-fibrinolytic properties. Altered endothelial function and participation in immune and autoimmune processes, such as antiphospholipid syndrome, are also potential mechanisms of Lp(a) involvement in LV pathogenesis. Lp(a) is part of the wound healing process; the possibility of Lp(a) serum elevation to reflect an acute-phase reagent in LV scenario is also considered. The objective of this review is to examine the possible association of lipoprotein(a) with LV pathogenesis, based on its effects on thrombogenesis, fibrinolysis and autoimmunity.
- Increased NY-ESO-1 Expression and Reduced Infiltrating CD3+T Cells in Cutaneous Melanoma(2015) GIAVINA-BIANCHI, Mara; GIAVINA-BIANCHI, Pedro; SOTTO, Mirian Nacagami; MUZIKANSKY, Alona; KALIL, Jorge; FESTA-NETO, Cyro; DUNCAN, Lyn M.NY-ESO-1 is a cancer-testis antigen aberrantly expressed in melanomas, which may serve as a robust and specific target in immunotherapy. NY-ESO-1 antigen expression, tumor features, and the immune profile of tumor infiltrating lymphocytes were assessed in primary cutaneous melanoma. NY-ESO-1 protein was detected in 20% of invasive melanomas (16/79), rarely in in situ melanoma (1/10) and not in benign nevi (0/20). Marked intratumoral heterogeneity of NY-ESO-1 protein expression was observed. NY-ESO-1 expression was associated with increased primary tumor thickness (P = 0.007) and inversely correlated with superficial spreading melanoma (P < 0.02). NY-ESO-1 expression was also associated with reduced numbers and density of CD3+ tumor infiltrating lymphocytes (P = 0.017). When NY-ESO-1 protein was expressed, CD3+ T cells were less diffusely infiltrating the tumor and were more often arranged in small clusters (P = 0.010) or as isolated cells (P = 0.002) than in large clusters of more than five lymphocytes. No correlation of NY-ESO-1 expression with gender, age, tumor site, ulceration, lymph node sentinel status, or survival was observed. NY-ESO-1 expression in melanoma was associated with tumor progression, including increased tumor thickness, and with reduced tumor infiltrating lymphocytes.