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
12 resultados
Resultados de Busca
Agora exibindo 1 - 10 de 12
- 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.
- 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.
- Epidermolysis Bullosa Pruriginosa: An Unusual Presentation of a Simplex Variant(2020) VISENTAINER, Lorena; KAZMAREK, Laura Moya; MAGALHAES, Renata Ferreira; STEINER, Carlos Eduardo; SOTTO, Mirian Nacagami; CINTRA, Maria Leticia; SOUZA, Elemir Macedo de
- Main autopsyfindings of visceral involvement by fatal mpox in patients with AIDS: necrotising nodular pneumonia, nodular ulcerative colitis, and diffuse vasculopathy(2023) DUARTE-NETO, Amaro Nunes; GONCALVES, Ana Maria; ELIODORO, Raissa Heloisa de Araujo; MARTINS, Wilker Dias; CLARO, Ingra Morales; VALENCA, Ian Nunes; PAES, Vitor Ribeiro; TEIXEIRA, Ralcyon; SZTAJNBOK, Jaques; SILVA, Ivan Leonardo Avelino Franca e; LEITE, Luiz Antonio Ferreira; MALAQUE, Ceila Maria Sant'Ana; BORGES, Luciana Marques Sansao; GONZALEZ, Mario Peribanez; BARRA, Luiz Alberto Costa; PEREIRA JUNIOR, Luiz Carlos; MELLO, Claudia Figueiredo; QUEIROZ, Wladimir; ATOMYA, Angela Naomi; FERNEZLIAN, Sandra de Morais; ALVES, Venancio Avancini Ferreira; LEITE, Katia Ramos Moreira; FERREIRA, Cristiane Rubia; SALDIVA, Paulo Hilario Nascimento; MAUAD, Thais; SILVA, Luiz Fernando Ferraz da; FARIA, Nuno R.; CORREA, Maria Cassia Jacinto Mendes; SABINO, Ester Cerdeira; SOTTO, Mirian Nacagami; DOLHNIKOFF, Marisa
- Methotrexate for refractory adult atopic dermatitis leads to alterations in cutaneous IL-31 and IL-31RA expression(2024) SAMORANO, Luciana Paula; MANFRERE, Kelly Cristina Gomes; PEREIRA, Naiura Vieira; TAKAOKA, Roberto; VALENTE, Neusa Yuriko Sakai; SOTTO, Mirian Nacagami; SILVA, Luiz Fernando Ferraz; SATO, Maria Notomi; AOKI, ValeriaBackground: Methotrexate (MTX) is an alternative treatment for patients with moderate/severe atopic dermatitis (AD). Objective: The authors evaluated the effect of MTX on the cutaneous expression of cytokines and chemokines that are involved in the inflammatory response in adult AD patients who received treatment with methotrexate for 24 weeks. Methods: The authors conducted a prospective single-institution cohort study with 12 adults with moderate/severe AD who received oral MTX (15 mg/wk for 24 wks) and 10 non-atopic matched controls. The comparison was made of skin biopsies of lesional and non-lesional skin, pre- and post MTX treatment. The authors analyzed mean epidermal thickness and expression of IL-31, IL-31RA, OSMR, TSLP, Ki67, IL-4 mRNA, IL-6, IL-10, TNF-alpha, IFN-gamma, TARC, and CCL-22. Results: There was a reduction in mean epidermal thickness (p = 0.021), an increase in IL-31RA expression (immunohistochemistry) in the epidermis (p = 0.016) and a decrease in IL-31 gene expression (p = 0.019) on lesional AD skin post-MTX treatment. No significant changes in the cutaneous expression of the other evaluated markers were identified. Study limitations: Small sample size and limited length of follow-up. Conclusions: Treatment with MTX in adults with moderate/severe AD reduced epidermal hyperplasia and changed the cutaneous expression of inflammatory cytokines and receptors that are mainly related to pruritus, including IL-31 and IL-31RA. (c) 2023 Published by Elsevier Espana, S.L.U. on behalf of Sociedade Brasileira de Dermatologia. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).
- Imbalanced IL-1B and IL-18 Expression in Sezary Syndrome(2023) MANFRERE, Kelly Cristina Gomes; TORREALBA, Marina Passos; FERREIRA, Frederico Moraes; SOUSA, Emanuella Sarmento Alho de; MIYASHIRO, Denis; TEIXEIRA, Franciane Mouradian Emidio; CUSTODIO, Ricardo Wesley Alberca; NAKAYA, Helder I.; RAMOS, Yasmin Alefe Leuzzi; SOTTO, Mirian Nacagami; WOETMANN, Anders; ODUM, Niels; DUARTE, Alberto Jose da Silva; SANCHES, Jose Antonio; SATO, Maria NotomiSezary syndrome (SS) is a rare and aggressive type of cutaneous T-cell lymphoma, with an abnormal inflammatory response in affected skin. The cytokines IL-1B and IL-18, as key signaling molecules in the immune system, are produced in an inactive form and cleave to the active form by inflammasomes. In this study, we assessed the skin, serum, peripheral mononuclear blood cell (PBMC) and lymph-node samples of SS patients and control groups (healthy donors (HDs) and idiopathic erythroderma (IE) nodes) to investigate the inflammatory markers IL-1B and IL-18 at the protein and transcript expression levels, as potential markers of inflammasome activation. Our findings showed increased IL-1B and decreased IL-18 protein expression in the epidermis of SS patients; however, in the dermis layer, we detected increased IL-18 protein expression. In the lymph nodes of SS patients at advanced stages of the disease (N2/N3), we also detected an enhancement of IL-18 and a downregulation of IL-1B at the protein level. Moreover, the transcriptomic analysis of the SS and IE nodes confirmed the decreased expression of IL1B and NLRP3, whereas the pathway analysis indicated a further downregulation of IL1B-associated genes. Overall, the present findings showed compartmentalized expressions of IL-1B and IL-18 and provided the first evidence of their imbalance in patients with Sezary syndrome.
- Inflammasome and Inflammatory Programmed Cell Death in Chromoblastomycosis(2023) PAGLIARI, Carla; KANASHIRO-GALO, Luciane; SOTTO, Mirian NacagamiChromoblastomycosis (CBM) is a chronic, progressive fungal disease of the skin and subcutaneous tissue caused by a group of dematiaceous fungi. Verrucous lesions present parasite-rich granulomas and predominance of a Th2 patterns of cytokines. The inflammasome constitutes a macromolecular protein complex that play a role in the activation of caspase 1 that cleaves pro-IL1 beta and pro-IL18, essential mediators of inflammation, and also activates pyroptosis. We intended to explore the presence and a possible role of inflammasome elements in cutaneous human lesions in CBM, considering the expression of IL1 beta, IL18, caspase 1, NLRP1, and also RIPK3, a key downstream component of necroptosis signaling. 35 skin biopsies of cutaneous lesions of verrucous form of CBM and 10 biopsies from normal skin were selected. The diagnosis was based on histological and clinical analysis. An immunohistochemical protocol was performed. The histopathological analysis evidenced epidermis with hyperkeratosis, irregular acanthosis, and micro abscesses. The dermis presented suppurative granulomas and inflammatory infiltrate composed by giant cells, macrophages, epithelioid cells, lymphocytes, and some eosinophils. Positive cells were distributed in the inflammatory infiltrate, with an increased number of cells expressing caspase 1, IL1 beta and IL18. Cells expressing RIPK3 and NLRP1 were less frequent. The intense presence of caspase 1, IL1 beta and IL18, allied to NLRP1 expression, suggest that inflammasome and pyroptosis could play a role in the immune response against fungal agents of CBM. Our results, allied to data from literature, could suggest that inflammasome-mediated response and pyroptosis could be a target to be explored to decrease CBM lesions.
- Plasmacytoid Dendritic Cells, the Expression of the Stimulator of Interferon Genes Protein (STING) and a Possible Role of Th17 Immune Response in Cervical Lesions Mediated by Human Papillomavirus(2023) JESUS, Ana Carolina Caetano; MENICONI, Maria Cristina Goncalves; GALO, Luciane Kanashiro; DUARTE, Maria Irma Seixas; SOTTO, Mirian Nacagami; PAGLIARI, CarlaHuman papillomavirus (HPV) is a virus with a DNA structure that specifically targets squamous epithelial cells. In individuals with a healthy immune system, HPV infection is typically resolved naturally, leading to spontaneous regression. However, when the viral genetic material integrates into the host DNA, it can disrupt the immune response and eventually give rise to neoplastic manifestations. Remarkably, HPV infection appears to activate a protein called Stimulator of Interferon genes (STING), which contributes to the infiltration of Treg Foxp3 + cells. This cellular response acts as a predisposing factor in patients with HPV, potentially exacerbating the progression of the infection. The STING is versatile in different circumstances and can play a role in the immune response as an anti-tumour therapeutic target in HPV-related carcinogenesis. The function of Th17 cells is ambiguous, depending on the microenvironment in the tumour. In this study, 46 biopsies of the uterine cervix of human immunodeficiency virus (HIV) positive patients were divided into three groups: I-cervicitis (10); II-low-grade intraepithelial neoplasia (26); III-moderate or severe intraepithelial neoplasia (10) and it was performed an immunohistochemical technique with the specific antibodies to HPV, CD123, STING and IL17. Immunostained cells were quantified and statistically analysed. Antigens of HPV were detected in the cervical intraepithelial neoplasia (CIN) groups and were absent in cervicitis group. The expression of CD123 was positive in 10.87% of the casuistic, with no statistical difference among groups. STING was present in the three groups. Group 1 presented an area fraction that varied from 3 to 20%, group 2 presented a variation of 3-23% and group 3 presented an area fraction between 4 and 12%. Cells expressing IL17 were present in three groups, more frequent in cervicitis. Considering that the casuistic is composed of women carrying HIV, this infectious agent could influence the numerical similarities of the cells studied among three groups, even in the absence of HPV. Stimulator of Interferon genes protein (STING) is versatile in different mechanisms in the immune response and may be a target in HPV-related carcinogenesis. Through immunohistochemistry it was detected IL17 in cervicitis and lesions with HPV. Also, CD123 + plasmacytoid cells seems to play a role both in cervicitis and lesions mediated by HPV.
- A Rare Association of Chronic Pulmonary Aspergillosis and Pulmonary Cryptococcosis as an Underlying Risk Factor(2023) SEKIGUCHI, William Kazunori; ALBUQUERQUE, Ronniel Morais; RAPOZO, Marjorie Marini; POLLY, Matheus; NASTRI, Ana Catharina de Seixas Santos; MAGRI, Marcello Mihailenko Chaves; OLIVEIRA, Vitor Falcao de; BERNARDI, Fabiola del Carlo; SOTTO, Mirian Nacagami
- Obesity Induces an Impaired Placental Antiviral Immune Response in Pregnant Women Infected with Zika Virus(2023) BRANCO, Anna Claudia Calvielli Castelo; OLIVEIRA, Emily Araujo De; PEREIRA, Natalli Zanete; ALBERCA, Ricardo Wesley; DUARTE-NETO, Amaro Nunes; SILVA, Luiz Fernando Ferraz Da; LUIZ, Fernanda Guedes; PEREIRA, Naiura Vieira; SOTTO, Mirian Nacagami; DEJANI, Naiara Naiana; RONDO, Patricia Helen Carvalho; AVVAD-PORTARI, Elyzabeth; VASCONCELOS, Zilton Farias Meira De; DUARTE, Alberto Jose da Silva; AZAMOR, Tamiris; SATO, Maria NotomiObesity is increasing in incidence worldwide, especially in women, which can affect the outcome of pregnancy. During this period, viral infections represent a risk to the mother, the placental unit, and the fetus. The Zika virus (ZIKV) outbreak in Brazil has been the cause of congenital Zika syndrome (CZS), with devastating consequences such as microcephaly in newborns. Herein, we analyzed the impact of maternal overweight/obesity on the antiviral factors' expression in the placental tissue of Zika-infected mothers. We accessed placentas from women with and without obesity from 34 public health units (Sao Paulo) and from Zika-infected mothers with and without obesity from the Clinical Cohort Study of ZIKV pregnant women (Rio de Janeiro, Brazil). We first verified that obesity, without infection, did not alter the constitutive transcriptional expression of antiviral factors or IFN type I/III expression. Interestingly, obesity, when associated with ZIKV infection, showed a decreased transcriptional expression of RIG-I and IFIH1 (MDA-5 protein precursor gene). At the protein level, we also verified a decreased RIG-I and IRF-3 expression in the decidual placenta from the Zika-infected obese group, regardless of microcephaly. This finding shows, for the first time, that obesity associated with ZIKV infection leads to an impaired type I IFN downstream signaling pathway in the maternal-fetal interface.