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Raquel Orfali
Laboratory of Dermatology and Immunodeficiencies (LIM-56), Department of Dermatology, Faculdade de Medicina FMUSP, Universidade de Sao Paulo, 01246-903 Sao Paulo, Brazil

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Journal article
Published: 10 May 2021 in Vaccines
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Psoriasis is an immune-mediated dermatosis usually associated with comorbidities. Treatment varies from topicals to systemic drugs and data on susceptibility to viral infections in psoriatic patients are scarce. The objectives of this study were to analyze psoriatic patients on different therapies who were at risk for COVID-19 for seroprevalence of SARS-COV-2, pro-inflammatory cytokine profile, comorbidities and outcomes in order to unveil the immunological mechanisms involved in the anti-viral response in patients with psoriasis. Seventy-five patients with psoriasis were divided according to treatment: immunobiologics, methotrexate, topicals and acitretin. Twenty healthy controls were included. Plasma samples were collected for: IgG SARS-COV-2 (ELISA); IL-27, IL-29 and IL-18 (ELISA); and IL-1β, IL-17A, IL-6 and TNF (cytometric array). Seropositivity for SARS-COV-2 was detected in 24 out of 75 psoriasis patients and did not relate to COVID-19 symptoms and/or hospitalization, despite associated comorbidities. Psoriasis patients who were asymptomatic for SARS-COV-2 exhibited immune imbalance with high levels of IL-18, IL-17A and IL-6, and low levels of IL-27 compared to healthy controls. Psoriasis groups showed significant increased cytokine levels only in the group with immunobiologics. Despite immune deviations and lower IL-27, which has a potential antiviral impact, psoriatic patients did not exhibit complications related to COVID-19. An understanding of this kind of proinflammatory profile of psoriatic patients and of the lack of severe outcomes for COVID-19 is essential to establish novel therapeutic approaches and preventive measures, including with regard to the concomitance of viral infections.

ACS Style

Tatiana Yendo; Maria Sato; Anna Branco; Anna Pietrobon; Franciane Teixeira; Yasmim Ramos; Ricardo Alberca; Cesar Valêncio; Vivian Arruda; Ricardo Romiti; Marcelo Arnone; André Hirayama; Alberto Duarte; Valeria Aoki; Raquel Orfali. Impact of Inflammatory Immune Dysfunction in Psoriasis Patients at Risk for COVID-19. Vaccines 2021, 9, 478 .

AMA Style

Tatiana Yendo, Maria Sato, Anna Branco, Anna Pietrobon, Franciane Teixeira, Yasmim Ramos, Ricardo Alberca, Cesar Valêncio, Vivian Arruda, Ricardo Romiti, Marcelo Arnone, André Hirayama, Alberto Duarte, Valeria Aoki, Raquel Orfali. Impact of Inflammatory Immune Dysfunction in Psoriasis Patients at Risk for COVID-19. Vaccines. 2021; 9 (5):478.

Chicago/Turabian Style

Tatiana Yendo; Maria Sato; Anna Branco; Anna Pietrobon; Franciane Teixeira; Yasmim Ramos; Ricardo Alberca; Cesar Valêncio; Vivian Arruda; Ricardo Romiti; Marcelo Arnone; André Hirayama; Alberto Duarte; Valeria Aoki; Raquel Orfali. 2021. "Impact of Inflammatory Immune Dysfunction in Psoriasis Patients at Risk for COVID-19." Vaccines 9, no. 5: 478.

Original article
Published: 12 June 2020 in Journal of the European Academy of Dermatology and Venereology
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Background 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 proinflammatory 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 analyzed by immunohistochemistry utilizing IL‐31, IL‐31RA, IL‐4, IL‐17 and TNF‐α 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: 1) Enhanced in situ expression of IL‐31 in PH samples, compared to PF and to PV (epidermis); 2) Cutaneous IL‐31RA expression in PH samples was higher than in PF, PV and HC groups (epidermis and dermis) ;3) 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‐α) in PH patients’ skin exhibited: 1) Enhanced IL‐4 expression, when compared to patients with PF (epidermis and dermis) and with PV (epidermis); 2) Augmented IL‐17 expression than PF and PV patients (epidermis); 3) Augmented expression of TNF‐α 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 proinflammatory 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.

ACS Style

Karina Lopes Morais; Denise Miyamoto; Raquel Leão Orfali; Celina Wakisaka Maruta; Claudia Giuli Santi; Mirian Nacagami Sotto; Luiz Fernando Ferraz Da Silva; Anna Cláudia Calvielli Castelo Branco; Maria Notomi Sato; Valeria Aoki. 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. Journal of the European Academy of Dermatology and Venereology 2020, 34, 2890 -2897.

AMA Style

Karina Lopes Morais, Denise Miyamoto, Raquel Leão Orfali, Celina Wakisaka Maruta, Claudia Giuli Santi, Mirian Nacagami Sotto, Luiz Fernando Ferraz Da Silva, Anna Cláudia Calvielli Castelo Branco, Maria Notomi Sato, Valeria Aoki. 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. Journal of the European Academy of Dermatology and Venereology. 2020; 34 (12):2890-2897.

Chicago/Turabian Style

Karina Lopes Morais; Denise Miyamoto; Raquel Leão Orfali; Celina Wakisaka Maruta; Claudia Giuli Santi; Mirian Nacagami Sotto; Luiz Fernando Ferraz Da Silva; Anna Cláudia Calvielli Castelo Branco; Maria Notomi Sato; Valeria Aoki. 2020. "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." Journal of the European Academy of Dermatology and Venereology 34, no. 12: 2890-2897.

Journal article
Published: 11 September 2019 in Scientific Reports
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Staphylococcus aureus colonizes the skin of atopic dermatitis (AD) individuals, but the impact of its enterotoxins on the chronic activation of CD4+ T cells demands further analysis. We aimed to analyze the CD4+ T cell anergy profile and their phenotypic and functional features through differential expression of cellular activation markers, cytokine production and response to staphylococcal enterotoxin A (SEA). A panel of 84 genes relevant to T cell anergy was assessed by PCR array in FACS-sorted CD4+ T cells, and the most prominent genes were validated by RT-qPCR. We evaluated frequencies of circulating CD4+ T cells secreting single or multiple (polyfunctional) cytokines (IL-17A, IL-22, TNF, IFN-γ, and MIP-1β) and expression of activation marker CD38 in response to SEA stimulation by flow cytometry. Our main findings indicated upregulation of anergy-related genes (EGR2 and IL13) promoted by SEA in AD patients, associated to a compromised polyfunctional response particularly in CD4+CD38+ T cells in response to antigen stimulation. The pathogenic role of staphylococcal enterotoxins in adult AD can be explained by their ability to downmodulate the activated effector T cell response, altering gene expression profile such as EGR2 induction, and may contribute to negative regulation of polyfunctional CD4+ T cells in these patients.

ACS Style

Raquel Leao Orfali; Fabio Seiti Yamada Yoshikawa; Luanda Oliveira; Natalli Zanete Pereira; Josenilson Feitosa De Lima; Yasmim Álefe Leuzzi Ramos; Alberto José Da Silva Duarte; Maria Notomi Sato; Valeria Aoki. Staphylococcal enterotoxins modulate the effector CD4+ T cell response by reshaping the gene expression profile in adults with atopic dermatitis. Scientific Reports 2019, 9, 13082 .

AMA Style

Raquel Leao Orfali, Fabio Seiti Yamada Yoshikawa, Luanda Oliveira, Natalli Zanete Pereira, Josenilson Feitosa De Lima, Yasmim Álefe Leuzzi Ramos, Alberto José Da Silva Duarte, Maria Notomi Sato, Valeria Aoki. Staphylococcal enterotoxins modulate the effector CD4+ T cell response by reshaping the gene expression profile in adults with atopic dermatitis. Scientific Reports. 2019; 9 (1):13082.

Chicago/Turabian Style

Raquel Leao Orfali; Fabio Seiti Yamada Yoshikawa; Luanda Oliveira; Natalli Zanete Pereira; Josenilson Feitosa De Lima; Yasmim Álefe Leuzzi Ramos; Alberto José Da Silva Duarte; Maria Notomi Sato; Valeria Aoki. 2019. "Staphylococcal enterotoxins modulate the effector CD4+ T cell response by reshaping the gene expression profile in adults with atopic dermatitis." Scientific Reports 9, no. 1: 13082.

Review
Published: 05 June 2019 in Toxins
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Atopic dermatitis (AD) is a chronic and inflammatory skin disease with intense pruritus and xerosis. AD pathogenesis is multifactorial, involving genetic, environmental, and immunological factors, including the participation of Staphylococcus aureus. This bacterium colonizes up to 30–100% of AD skin and its virulence factors are responsible for its pathogenicity and antimicrobial survival. This is a concise review of S. aureus superantigen-activated signaling pathways, highlighting their involvement in AD pathogenesis, with an emphasis on skin barrier disruption, innate and adaptive immunity dysfunction, and microbiome alterations. A better understanding of the combined mechanisms of AD pathogenesis may enhance the development of future targeted therapies for this complex disease.

ACS Style

Fabio Seiti Yamada Yoshikawa; Josenilson Feitosa De Lima; Maria Notomi Sato; Yasmin Álefe Leuzzi Ramos; Valeria Aoki; Raquel Leao Orfali. Exploring the Role of Staphylococcus Aureus Toxins in Atopic Dermatitis. Toxins 2019, 11, 321 .

AMA Style

Fabio Seiti Yamada Yoshikawa, Josenilson Feitosa De Lima, Maria Notomi Sato, Yasmin Álefe Leuzzi Ramos, Valeria Aoki, Raquel Leao Orfali. Exploring the Role of Staphylococcus Aureus Toxins in Atopic Dermatitis. Toxins. 2019; 11 (6):321.

Chicago/Turabian Style

Fabio Seiti Yamada Yoshikawa; Josenilson Feitosa De Lima; Maria Notomi Sato; Yasmin Álefe Leuzzi Ramos; Valeria Aoki; Raquel Leao Orfali. 2019. "Exploring the Role of Staphylococcus Aureus Toxins in Atopic Dermatitis." Toxins 11, no. 6: 321.

Urticaria
Published: 01 April 2019 in Anais Brasileiros de Dermatologia
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Urticarias are frequent diseases, with 15% to 20% of the population presenting at least one acute episode in their lifetime. Urticaria are classified in acute ( ≤ 6 weeks) or chronic (> 6 weeks). They may be induced or spontaneous. To verify the diagnostic and therapeutic recommendations in chronic spontaneous urticaria (CSU), according to the experience of Brazilian experts, regarding the available guidelines (international and US). A questionnaire was sent to Brazilian experts, with questions concerning diagnostic and therapeutic recommendations for CSU in adults. Sixteen Brazilian experts answered the questionnaire related to diagnosis and therapy of CSU in adults and data were analyzed. Final text was written, considering the available guidelines (International and US), adapted to the medical practices in Brazil. Diagnostic work up in CSU is rarely necessary. Biopsy of skin lesion and histopathology may be indicated to rule out other diseases, such as, urticarial vasculitis. Other laboratory tests, such as complete blood count, CRP, ESR and thyroid screening. Treatment of CSU includes second-generation anti-histamines (sgAH) at licensed doses, sgAH two, three to fourfold doses (non-licensed) and omalizumab. Other drugs, such as, cyclosporine, immunomodulatory drugs and immunosuppressants may be indicated (non-licensed and with limited scientific evidence). Most of the Brazilian experts in this study partially agreed with the diagnostic and therapeutic recommendations of the International and US guidelines. They agreed with the use of sgAH at licensed doses. Increase in the dose to fourfold of sgAH may be suggested with restrictions, due to its non-licensed dose. Sedating anti-histamines, as suggested by the US guideline, are indicated by some of the Brazilian experts, due to its availability. Adaptations are mandatory in the treatment of CSU, due to scarce or lack of other therapeutic resources in the public health system in Brazil, such as omalizumab or cyclosporine.

ACS Style

Paulo Ricardo Criado; Celina Wakisaka Maruta; Alice De Oliveira De Avelar Alchorne; Andréa Machado Coelho Ramos; Bernardo Gontijo; Josemir Belo Dos Santos; Luis Eduardo Agner Machado Martins; Maria Cecília Rivitti-Machado; Maria Regina Cavariani Silvares; Mario Cezar Pires; Patricia Karla De Souza; Raquel Leão Orfali; Renan Rangel Bonamigo; Roberta Buense Bedrikow; Roberta Fachini Jardim Criado; Zilda Najjar Prado De Oliveira. Consensus on the diagnostic and therapeutic management of chronic spontaneous urticaria in adults - Brazilian Society of Dermatology. Anais Brasileiros de Dermatologia 2019, 94, 56 -66.

AMA Style

Paulo Ricardo Criado, Celina Wakisaka Maruta, Alice De Oliveira De Avelar Alchorne, Andréa Machado Coelho Ramos, Bernardo Gontijo, Josemir Belo Dos Santos, Luis Eduardo Agner Machado Martins, Maria Cecília Rivitti-Machado, Maria Regina Cavariani Silvares, Mario Cezar Pires, Patricia Karla De Souza, Raquel Leão Orfali, Renan Rangel Bonamigo, Roberta Buense Bedrikow, Roberta Fachini Jardim Criado, Zilda Najjar Prado De Oliveira. Consensus on the diagnostic and therapeutic management of chronic spontaneous urticaria in adults - Brazilian Society of Dermatology. Anais Brasileiros de Dermatologia. 2019; 94 (2):56-66.

Chicago/Turabian Style

Paulo Ricardo Criado; Celina Wakisaka Maruta; Alice De Oliveira De Avelar Alchorne; Andréa Machado Coelho Ramos; Bernardo Gontijo; Josemir Belo Dos Santos; Luis Eduardo Agner Machado Martins; Maria Cecília Rivitti-Machado; Maria Regina Cavariani Silvares; Mario Cezar Pires; Patricia Karla De Souza; Raquel Leão Orfali; Renan Rangel Bonamigo; Roberta Buense Bedrikow; Roberta Fachini Jardim Criado; Zilda Najjar Prado De Oliveira. 2019. "Consensus on the diagnostic and therapeutic management of chronic spontaneous urticaria in adults - Brazilian Society of Dermatology." Anais Brasileiros de Dermatologia 94, no. 2: 56-66.

Atopic dermatitis
Published: 01 April 2019 in Anais Brasileiros de Dermatologia
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Keywords: Atopic dermatitis; Interleukins; Inflammation; Keratinocytes; Skin barrier

ACS Style

Valeria Aoki; Daniel Lorenzini; Raquel Leão Orfali; Mariana Colombini Zaniboni; Zilda Najjar Prado De Oliveira; Maria Cecília Rivitti-Machado; Roberto Takaoka; Magda Blessmann Weber; Tania Cestari; Bernardo Gontijo; Andrea Machado Coelho Ramos; Claudia Marcia De Resende Silva; Silmara Da Costa Pereira Cestari; Silvia Souto-Mayor; Francisca Regina Carneiro; Ana Maria Mosca De Cerqueira; Cristina Laczynski; Mario Cezar Pires. Consensus on the therapeutic management of atopic dermatitis - Brazilian Society of Dermatology. Anais Brasileiros de Dermatologia 2019, 94, 67 -75.

AMA Style

Valeria Aoki, Daniel Lorenzini, Raquel Leão Orfali, Mariana Colombini Zaniboni, Zilda Najjar Prado De Oliveira, Maria Cecília Rivitti-Machado, Roberto Takaoka, Magda Blessmann Weber, Tania Cestari, Bernardo Gontijo, Andrea Machado Coelho Ramos, Claudia Marcia De Resende Silva, Silmara Da Costa Pereira Cestari, Silvia Souto-Mayor, Francisca Regina Carneiro, Ana Maria Mosca De Cerqueira, Cristina Laczynski, Mario Cezar Pires. Consensus on the therapeutic management of atopic dermatitis - Brazilian Society of Dermatology. Anais Brasileiros de Dermatologia. 2019; 94 (2):67-75.

Chicago/Turabian Style

Valeria Aoki; Daniel Lorenzini; Raquel Leão Orfali; Mariana Colombini Zaniboni; Zilda Najjar Prado De Oliveira; Maria Cecília Rivitti-Machado; Roberto Takaoka; Magda Blessmann Weber; Tania Cestari; Bernardo Gontijo; Andrea Machado Coelho Ramos; Claudia Marcia De Resende Silva; Silmara Da Costa Pereira Cestari; Silvia Souto-Mayor; Francisca Regina Carneiro; Ana Maria Mosca De Cerqueira; Cristina Laczynski; Mario Cezar Pires. 2019. "Consensus on the therapeutic management of atopic dermatitis - Brazilian Society of Dermatology." Anais Brasileiros de Dermatologia 94, no. 2: 67-75.

Journal article
Published: 27 April 2018 in Scientific Reports
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Atopic dermatitis (AD) is a chronic inflammatory immune-mediated skin disease characterized by skin colonization by Staphylococcus aureus. Interleukin (IL)-22, in cooperation with IL-17, triggers antimicrobial peptide elaboration and enhances certain immunological responses. In AD, IL-22 is related to epidermal hyperplasia, keratinocyte apoptosis, and inhibition of antimicrobial peptide (AMP) production. We aimed to evaluate the impact of staphylococcal enterotoxins on the Tc22/Th22 induction in the peripheral blood of AD patients and on CD4+/CD8+ T cells expressing IL-22 in AD skin. Our study showed inhibition of the staphylococcal enterotoxins A and B (SEA and SEB) response by Th22 (CD4+IL-22+IL-17A−IFN-γ−) cells in AD patients. In contrast, Tc22 (CD8+IL-22+IL-17A−IFN-γ−) cells were less susceptible to the inhibitory effects of staphylococcal enterotoxins and exhibited an enhanced response to the bacterial stimuli. In AD skin, we detected increased IL-22 transcript expression and T lymphocytes expressing IL-22. Together, our results provide two major findings in response to staphylococcal enterotoxins in adults with AD: dysfunctional CD4+ IL-22 secreting T cells and increased Tc22 cells. Our hypothesis reinforces the relevance of CD8 T cells modulated by staphylococcal enterotoxins as a potential source of IL-22 in adults with AD, which is relevant for the maintenance of immunological imbalance.

ACS Style

Raquel Leão Orfali; Luanda Oliveira; Josenilson Feitosa De Lima; Gabriel Costa De Carvalho; Yasmim Alefe Leuzzi Ramos; Nátalli Zanete Pereira; Naiura Vieira Pereira; Mariana Colombini Zaniboni; Mirian Nacagami Sotto; Alberto José Da Silva Duarte; Maria Notomi Sato; Valeria Aoki. Staphylococcus aureus enterotoxins modulate IL-22-secreting cells in adults with atopic dermatitis. Scientific Reports 2018, 8, 6665 .

AMA Style

Raquel Leão Orfali, Luanda Oliveira, Josenilson Feitosa De Lima, Gabriel Costa De Carvalho, Yasmim Alefe Leuzzi Ramos, Nátalli Zanete Pereira, Naiura Vieira Pereira, Mariana Colombini Zaniboni, Mirian Nacagami Sotto, Alberto José Da Silva Duarte, Maria Notomi Sato, Valeria Aoki. Staphylococcus aureus enterotoxins modulate IL-22-secreting cells in adults with atopic dermatitis. Scientific Reports. 2018; 8 (1):6665.

Chicago/Turabian Style

Raquel Leão Orfali; Luanda Oliveira; Josenilson Feitosa De Lima; Gabriel Costa De Carvalho; Yasmim Alefe Leuzzi Ramos; Nátalli Zanete Pereira; Naiura Vieira Pereira; Mariana Colombini Zaniboni; Mirian Nacagami Sotto; Alberto José Da Silva Duarte; Maria Notomi Sato; Valeria Aoki. 2018. "Staphylococcus aureus enterotoxins modulate IL-22-secreting cells in adults with atopic dermatitis." Scientific Reports 8, no. 1: 6665.