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
76 resultados
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- Mutational signatures and increased retrotransposon insertions in xeroderma pigmentosum variant skin tumors(2023) CORRADI, Camila; VILAR, Juliana B.; BUZATTO, Vanessa C.; SOUZA, Tiago A. de; CASTRO, Ligia P.; MUNFORD, Veridiana; VECCHI, Rodrigo De; GALANTE, Pedro A. F.; ORPINELLI, Fernanda; MILLER, Thiago L. A.; BUZZO, Jose L.; SOTTO, Mirian N.; SALDIVA, Paulo; OLIVEIRA, Jocelanio W. de; CHAIBUB, Sulamita C. W.; SARASIN, Alain; MENCK, Carlos F. M.This manuscript describes the genetic alterations found in the skin tumors of XP-V patients deficient in translesion synthesis. The alterations include mutation signatures and retrotransposition insertions, which provide mechanistic information about DNA polymerase eta functions. Xeroderma pigmentosum variant (XP-V) is an autosomal recessive disease with an increased risk of developing cutaneous neoplasms in sunlight-exposed regions. These cells are deficient in the translesion synthesis (TLS) DNA polymerase eta, responsible for bypassing different types of DNA lesions. From the exome sequencing of 11 skin tumors of a genetic XP-V patients' cluster, classical mutational signatures related to sunlight exposure, such as C>T transitions targeted to pyrimidine dimers, were identified. However, basal cell carcinomas also showed distinct C>A mutation spectra reflecting a mutational signature possibly related to sunlight-induced oxidative stress. Moreover, four samples carry different mutational signatures, with C>A mutations associated with tobacco chewing or smoking usage. Thus, XP-V patients should be warned of the risk of these habits. Surprisingly, higher levels of retrotransposon somatic insertions were also detected when the tumors were compared with non-XP skin tumors, revealing other possible causes for XP-V tumors and novel functions for the TLS polymerase eta in suppressing retrotransposition. Finally, the expected high mutation burden found in most of these tumors renders these XP patients good candidates for checkpoint blockade immunotherapy.
- Amantadine-Induced Livedo Racemosa(2016) CRIADO, Paulo Ricardo; ALAVI, Afsaneh; VALENTE, Neusa Yuriko Sakai; SOTTO, Mirian NacagamiAlthough livedo reticularis is a known adverse effect of amantadine, only limited studies have addressed this association. Livedo racemosa in contrast to livedo reticularis is characterized by a striking violaceous netlike pattern of the skin similar to livedo reticularis with a different histopathology and morphology (irregular, broken circular segments). In this case report, we present 2 cases of livedo racemosa and edema of lower extremities following amantadine treatment. The cutaneous biopsies in both cases showed intraluminal thrombi in subcutaneous blood vessels without evidence of vasculitis, which is consistent with livedo racemosa.
- Lacaziosis: immunohistochemical evaluation of elements of the humoral response in cutaneous lesions(2020) KANASHIRO-GALO, Luciane; ALEXANDRE, Ariane Fernandes; TAFURI, Wagner Luiz; BARBOZA, Tania Cristina; QUARESMA, Juarez Antonio Simoes; BRITO, Arival Cardoso de; NASCIMENTO, Gabriela Yasmin Francisca da Silva do; SANTOS FILHO, Antonio Marques dos; SOTTO, Mirian Nacagami; PAGLIARI, CarlaLacaziosis is a cutaneous mycosis caused by the fungus Lacazia loboi, described in different countries of Latin America and prevalent in the Amazon region. The ineffective immune response against the agent seems to be related to a Th2 pattern of cytokines. There are few reports exploring elements of the humoral response in these lesions. Our aim was to investigate some elements focusing on 13 cells, plasma cells and local expression of IgG and IgM antibodies. Forty skin biopsies of lower limbs were selected. The diagnosis of lacaziosis was based on direct mycological examination and histological analysis. The visualization of fungal cells was improved by using Gridley's staining. An immunohistochemical protocol was performed to detect the expression of B cells, plasma cells. IgG and IgM. A double staining was performed to explore the presence of yeasts in the cytoplasm of keratinocytes, using an anti-AE1 AE3 antibody over Gridley's staining. The inflammatory infiltrate consisted of macrophages, multinucleated giant cells, lymphocytes, and fibrosis. Fungal cells were frequent in the stratum corneum and in both, the dermis and, in 50% of the specimens, also in the epidermis. Cells expressing IgG were more abundant when compared to cells expressing IgM. B cells and the presence of IgG might indicate that the humoral response promotes a Th2 immune response resulting in an anti-inflammatory phenotype. Our results lead us to suggest a possible role of B cells and immunoglobulins in the mechanisms of lacaziosis pathogenesis.
- Unilateral Livedoid Vasculopathy Associated With Involutional Phase of Cutaneous Infantile Hemangioma: The Connection to Coagulation Disorders(2013) CRIADO, Paulo Ricardo; ALAVI, Afsaneh; HALPERN, Ilana; SOTTO, Mirian Nacagami; KIRSNER, Robert S.Livedoid vasculopathy is a bilateral painful and recurrent cutaneous ulcerative disorder of the legs that leads to atrophie blanche, atrophic white-porcelain scars, and is associated with disorders of fibrinolysis and/or coagulation. We present a young boy with an association between livedoid vasculopathy in the area of a previous involuted cutaneous hemangioma. We found 4 uncommon abnormalities associated with thrombo-occlusive events: heterozygous 20210 AG genotype of prothrombin, reduced activity of anticoagulation proteins C and S, and elevated lipoprotein (a).
- Macrophage subtypes in recurrent nodular basal cell carcinoma after Mohs micrographic surgery(2017) PADOVEZE, Emerson H.; CHIACCHIO, Nilton Di; OCAMPO-GARZA, Jorge; CERNEA, Selma S.; BELDA, Walter; SOTTO, Mirian N.BackgroundThe macrophages associated with solid tumors are related to the progression or regression of tumors, depending on the differentiation in M1 or M2. M2 subtype promotes angiogenesis, remodeling, and tissue repair (tumor proliferation). In contrast, M1 produces toxic mediators and presents antigens, destroying microorganisms and tumor cells. The microenvironment of most aggressive forms of basal cell carcinoma (BCC) shows an increase in macrophages due to M2 phenotype compared to noninvasive forms. The treatment of nodular BCC by Mohs micrographic surgery (MMS) provides high cure rates, but relapses can occur. AimsTo compare the total population of macrophages and their subpopulations M1 and M2 in cases of recurrent and nonrecurrent nodular BCC after excision by MMS. Materials & MethodsHistological sections obtained from paraffin blocks of nine cases of recurrent nodular BCC after MMS and 18 cases of nonrecurrent nodular BCC operated by MMS were immunostained for iNOS, CD204, CD163, and CD68. The expression of these markers was analyzed by image analysis. ResultsNo significant differences were found between the groups in relation to the average percentage of M1 cells, M2 cells, and total cells. Discussion and ConclusionA relationship was not seen between tumor-associated macrophages (TAM) and tumor recurrence.
- 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.
- M2-Polarized Macrophages Determine Human Cutaneous Lesions in Lacaziosis(2020) BARBOZA, Tania Cristina; SOTTO, Mirian Nacagami; KANASHIRO-GALO, Luciane; BRITO, Arival Cardoso de; DUARTE, Maria Irma Seixas; QUARESMA, Juarez Antonio Simoes; PAGLIARI, CarlaLacaziosis is a cutaneous chronic mycosis caused by Lacazia loboi. Macrophages are important cells in the host immune response in fungal infections. The macrophage population exhibits strong plasticity that varies according to the stimuli in the microenvironment of lesions M1 profile promotes a Th1 pattern of cytokines and a microbicidal function and M2 is related to Th2 cytokines and immunomodulatory response. We investigated the population of M1 and M2 polarized macrophages in human cutaneous lesions. A total of 27 biopsies from human lesions were submitted to an immunohistochemistry protocol using antibodies to detect M1 and M2 macrophages (Arginase-1, CD163, iNOS, RBP-J and cMAF). We could observe high number of cells expressing Arginase1, CD163 and c-MAF that correspond to elements of the M2 profile of macrophage, over iNOS and RBP-J (elements of the M1 profile). The results suggest a predominant phenotype of M2 macrophages, which have an immunomodulatory role and probably contributing to chronicity of Lacaziosis.
- Outlining the skin-homing and circulating CLA+NK cells in patients with severe atopic dermatitis(2024) LIMA, Josenilson Feitosa de; TEIXEIRA, Franciane Mouradian Emidio; RAMOS, Yasmim alefe Leuzzi; CARVALHO, Gabriel Costa de; BRANCO, Anna Claudia Calvielli Castelo; PEREIRA, Naiura Vieira; SOTTO, Mirian Nacagami; AOKI, Valeria; SATO, Maria Notomi; ORFALI, Raquel LeaoAtopic dermatitis (AD) is a complex, multifactorial skin disease, characterized by pruritus and predominant Th2 inflammation. Innate immune cells may play a role in AD development and are composed of granulocytes, macrophages, innate-like T cells, and innate lymphoid cells. This study investigates the phenotypic and functional profile of circulating CLA(+) natural killer (NK) cells and its role in the skin-homing to NK cells infiltrated in adults' skin with AD. We selected 44 AD patients and 27 non-AD volunteers for the study. The results showed increased frequencies of both CLA(+)CD56(bright) and CLA(+)CD56(dim) NK cell populations in the peripheral blood, mainly in severe AD patients. Upon SEB stimulation, we observed an augmented percentage of CLA(+)CD56(dim) NK cells expressing CD107a, IFN-gamma, IL-10, and TNF, reinforcing the role of staphylococcal enterotoxins in AD pathogenesis. Additionally, we demonstrated increased dermal expression of both NK cell markers NCAM-1/CD56 and pan-granzyme, corroborating the skin-homing, mostly in severe AD. Further studies are necessary to elucidate the potential role of NK cells in the chronification of the inflammatory process in AD skin, as well as their possible relationship with staphylococcal enterotoxins, and as practicable therapeutic targets.
- 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.
- 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.