ARIANA CAMPOS YANG
Projetos de Pesquisa
Unidades Organizacionais
Instituto Central, Hospital das Clínicas, Faculdade de Medicina - Médico
LIM/60 - Laboratório de Imunologia Clínica e Alergia, Hospital das Clínicas, Faculdade de Medicina
LIM/60 - Laboratório de Imunologia Clínica e Alergia, Hospital das Clínicas, Faculdade de Medicina
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- Eosinophilic Esophagitis: Latent Disease in Patients with Anaphylactic Reaction to Cow's Milk(2018) BARBOSA, Adriana C.; CASTRO, Fabio Morato; MEIRELES, Paula Rezende; ARRUDA, L. Karla; CARDOSO, Silvia Regina; KALIL, Jorge; YANG, Ariana C.BACKGROUND: Food allergy and eosinophilic esophagitis are a substantial and evolving public health issue. Clinicians should know the relationship between these diseases and how one may predispose to the other. This can help minimize misdiagnosis. OBJECTIVE: The objective of this study was to assess esophageal eosinophilia and eosinophilic esophagitis frequency in patients with persistent cow's milk allergy and anaphylaxis manifestations. METHODS: Patients with persistent cow's milk allergy with anaphylaxis manifestations were enrolled from 2012 through 2016 at the Sao Paulo University Hospital, Brazil. All of them were submitted to endoscopy despite the presence or absence of gastrointestinal symptoms. Demographics data, atopic comorbidities, medication use, endoscopic findings, and esophageal eosinophilia frequency were evaluated. RESULTS: Eighty-nine patients were selected. The median age was 8 years. It was observed that 34 of 89 patients (38.2%; 95% confidence interval [CI]: 28.14%-49.16%) presented with esophageal eosinophilia. Five patients (7.1%) presented proton pump inhibitor-responsive esophageal eosinophilia, and 10 patients (14.2%) presented eosinophilic esophagitis. We found that 29.4% were asymptomatic patients, 23.5% had nonspecific symptoms, 23.5% had persistent typical symptoms, and 23.5% had intermittent typical symptoms. There was an association with inflammatory endoscopy findings in 21 patients (61.7%). CONCLUSIONS: This description demands scientific attention because it is the highest frequency of esophageal eosinophilia yet described in a group of patients with cow's milk allergy presenting with anaphylaxis. Eosinophilic esophagitis is a condition that can coexist ""silently"" with an IgE-mediated food allergy and is most often underestimated and under-diagnosed. (C) 2017 American Academy of Allergy, Asthma & Immunology
- Novel allergens from ancient foods: Man e 5 from manioc (Manihot esculenta Crantz) cross reacts with Hev b 5 from latex(2013) SANTOS, Keity Souza; GADERMAIER, Gabriele; VEJVAR, Eva; ARCURI, Helen Andrade; GALVAO, Clovis Eduardo; YANG, Ariana Campos; RESENDE, Virginia Maria Ferreira; MARTINS, Carlo de Oliveira; HIMLY, Martin; MARI, Adriano; LISO, Marina; POMPONI, Debora; BREITENEDER, Heimo; WAGNER, Stefan; KALIL, Jorge; FERREIRA, Fatima; CASTRO, Fabio Fernandes MoratoScope Manioc (Manihot esculenta) is a tuber mainly consumed in the Southern Hemisphere and used worldwide by food and chemistry industry. We aimed to recombinantly produce and characterize the first manioc allergen and evaluate its IgE reactivity in sera of Brazilian and Italian patients. Methods and results The molecule, termed Man e5, was expressed in E. coli, characterized by amino acid analysis, mass spectrometry, circular dichroism, HPLC, and dynamic light scattering. A tertiary structural model of the protein was produced using bioinformatics and susceptibility to pepsin digestion was analyzed in vitro. Based on its high content of charged residues, heat stability, flexibility and lack of secondary structure elements, the allergen was determined a member of the intrinsically disordered protein family. Brazilian patients were selected based on manioc allergy and Italians based on latex allergy and sensitization to Hev b 5.71% of Brazilians and 40% of Italians were in vitro IgE positive to Man e5. Cross-inhibition assays suggest a possible involvement of this allergen in the latex-fruit syndrome. Conclusion Man e5, the first purified allergen from manioc demonstrates IgE cross-reactivity with Hev b 5. Data suggest Hev b 5 might act as primary sensitizer and could therefore lead to allergic manifestations upon manioc consumption without prior exposition.
- Clinical Features and Disease Management in Adult Patients With Atopic Dermatitis Receiving Care at Reference Hospitals in Brazil: the ADAPT Study(2021) ARRUDA, L. K.; YANG, A. C.; AOKI, V; CRIADO, R. F. J.; PIRES, M. C.; LUPI, O.; FABRICIO, L. H. Z.; RICHMAN, D.; SILVI, S.Background: Atopic dermatitis is a chronic inflammatory skin disease with a prevalence of 0.02% to 8.1% in adults. Adult patients with moderate-to-severe atopic dermatitis are affected by frequent relapses and a significant disease burden. Objective: To determine the clinical, immunological, and therapeutic profile of Brazilian adults with atopic dermatitis. Methods: A multicenter, observational, retrospective, descriptive registry-based study was conducted at reference hospitals between December 2016 and October 2017. The data collected were demographics, personal and family history of atopic diseases, clinical manifestations, laboratory tests, disease severity and management. Results: Of the 187 patients included in the analysis, 56.1% were female and 71.7% were White, with a mean age of 24.7 years. Mean follow-up was 9 years. Asthma or other allergic diseases were reported by 80.2% of patients. The main comorbidity was hypertension (10.2%), and common disease manifestations included pruritus and erythema. Lesions generally affected flexural and nonflexural areas, with typical morphology. Around 83% of patients had moderate-to-severe disease, and 8.6% reported at least 1 hospitalization. Most patients received topical and/or systemic pharmacological therapies, including omalizumab (5.9%); 4.3% received phototherapy. Moreover, 66.8% of patients received adjuvant therapy, and 79.1% changed or discontinued treatment for atopic dermatitis due to remission (46.5%), poor effectiveness (33.7%), or lack of adherence (12.9%). Most patients presented characteristics of type 2 inflammation, with immunoglobulin E levels above 100 IU/mL (94.4%) and peripheral blood eosinophils above 5% (55.9%). Conclusion: Brazilian adult patients with severe atopic dermatitis need treatment to efficiently control the disease and improve quality of life.
- Evaluating the impacts of relaxation and mutation in the SARS-CoV-2 on the COVID-19 epidemic based on a mathematical model: a case study of Sao Paulo State (Brazil)(2021) YANG, Hyun Mo; LOMBARDI JUNIOR, Luis Pedro; CASTRO, Fabio Fernandes Morato; YANG, Ariana CamposAt the beginning of 2020, SARS-CoV-2 spread to all continents, and many countries adopted quarantine to flatten the COVID-19 outbreak, resulting in the containment of transmission. However, the persistent transmission of SARS-CoV-2, an RNA virus, resulted in the appearance of mutations in the original virus. The appearance of more virulent mutations in different regions of the world resulted in an increased number of severe COVID-19 cases. A mathematical model based on the COVID-19 natural history encompassing the mutations was applied to evaluate the SARS-CoV-2 epidemic. The model parameters were fitted against the observed data from Sao Paulo State (Brazil) considering quarantine, relaxation, and mutation. The estimated data from Sao Paulo State showed that the original SARS-CoV-2 transmission better explained the COVID-19 epidemic during the quarantine. However, the increased number of fatalities beyond that predicted by the relaxation indicated the occurrence of mutations. Hence, the relaxation in association with the transmission of a more virulent SARS-CoV-2 better estimated the COVID-19 epidemic from February 26, 2020, to June 15, 2021, in Sao Paulo State.
- Mathematical modeling of the transmission of SARS-CoV-2-Evaluating the impact of isolation in SAo Paulo State (Brazil) and lockdown in Spain associated with protective measures on the epidemic of CoViD-19(2021) YANG, Hyun Mo; LOMBARDI JUNIOR, Luis Pedro; CASTRO, Fabio Fernandes Morato; YANG, Ariana CamposCoronavirus disease 2019 (CoViD-19), with the fatality rate in elder (60 years old or more) being much higher than young (60 years old or less) patients, was declared a pandemic by the World Health Organization on March 11, 2020. A mathematical model considering young and elder subpopulations under different fatality rates was formulated based on the natural history of CoViD-19 to study the transmission of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The model considered susceptible, exposed, asymptomatic, pre-symptomatic, mild CoViD-19, severe CoViD-19, and recovered compartments, besides compartments of isolated individuals and those who were caught by test. This model was applied to study the epidemiological scenario resulting from the adoption of quarantine (isolation or lockdown) in many countries to control the rapid propagation of CoViD-19. We chose as examples the isolation adopted in SAo Paulo State (Brazil) in the early phase but not at the beginning of the epidemic, and the lockdown implemented in Spain when the number of severe CoViD-19 cases was increasing rapidly. Based on the data collected from SAo Paulo State and Spain, the model parameters were evaluated, and we obtained a higher estimation for the basic reproduction number R-0 (9.24 for SAo Paulo State, and 8 for Spain) compared to the currently accepted estimation of R-0 around 2 using the SEIR (susceptible, exposed, infectious, and recovered compartments) model. In comparison with the lockdown in Spain, the relatively early adoption of the isolation in SAo Paulo State resulted in enlarging the period of the first wave of the epidemic and delaying its peak. The model allowed to explain the flattening of the epidemic curves by quarantine when associated with the protective measures (face mask, washing hands with alcohol and gel, and social distancing) adopted by the population. The description of the epidemic under quarantine and protections can be a background to foreseen the epidemiological scenarios from the release strategies, which can help guide public health policies by decision-makers.
- Mathematical model describing CoViD-19 in Sao Paulo, Brazil - evaluating isolation as control mechanism and forecasting epidemiological scenarios of release(2020) YANG, H. M.; LOMBARDI JUNIOR, L. P.; CASTRO, F. F. M.; YANG, A. C.In Sao Paulo, Brazil, the first case of coronavirus disease 2019 (CoViD-19) was confirmed on 26 February, the first death due to CoViD-19 was registered on 16 March, and on 24 March, Sao Paulo implemented the isolation of persons in non-essential activities. A mathematical model was formulated based on non-linear ordinary differential equations considering young (60 years old or less) and elder (60 years old or more) subpopulations, aiming to describe the introduction and dissemination of the new coronavirus in Sao Paulo. This deterministic model used the data collected from Sao Paulo to estimate the model parameters, obtainingR(0)= 6.8 for the basic reproduction number. The model also allowed to estimate that 50% of the population of Sao Paulo was in isolation, which permitted to describe the current epidemiological status. The goal of isolation implemented in Sao Paulo to control the rapid increase of the new coronavirus epidemic was partially succeeded, concluding that if isolation of at least 80% of the population had been implemented, the collapse in the health care system could be avoided. Nevertheless, the isolated persons must be released one day. Based on this model, we studied the potential epidemiological scenarios of release by varying the proportions of the release of young and elder persons. We also evaluated three different strategies of release: All isolated persons are released simultaneously, two and three releases divided in equal proportions. The better scenarios occurred when young persons are released, but maintaining elder persons isolated for a while. When compared with the epidemic without isolation, all strategies of release did not attain the goal of reducing substantially the number of hospitalisations due to severe CoViD-19. Hence, we concluded that the best decision must be postponing the beginning of the release.
- Underlying IPEX syndrome in a patient with idiopathic juvenile arthritis and vitiligo(2022) MENDONCA, Leonardo Oliveira; CHUSTER, Adriana Pitchon dos Reis; DORNA, Mayra Barros; BARROS, Samar Freschi; ALVES, Janaina Baptista; GONCALVES, Victor Lucas; YANG, Ariana Campos; KALIL, Jorge; TOLEDO-BARROS, Myrthes Anna Maragna; KOKRON, Cristina MariaBackground: IPEX syndrome is an X-linked inborn error of immunity clinically characterized by the triad of: enteropathy, polyendocrinopathy and eczema. However many other clinical presentations lacking the triad above described have been reported what underpin the need of careful clinical suspicion, immunological evaluation and genetic sequencing. Case presentation: Here we report a case of a Brazilian boy with severe eczema as the first and only presentation requiring cyclosporin therapy. Progressive and cumulative symptoms of arthritis and enteropathy lead to the suspicion of an inborn error of immunity. Peripheral FOXP3 expression was normal (CD127-/CD4+/CD25+/FOXP3+-396 cells-63%) and a pathogenic mutation in FOXP3 gene (c.1150G > A; p.Ala384Thr), confirmed the diagnosis of IPEX syndrome. Conclusions: IPEX syndrome should be suspected in patients presenting with severe eczema associated or not with other autoimmune/hyper inflammatory diseases in life. Our study also reinforces that FOXP3 expression by flowcytometry seems not to be a good screening method, and genetic sequencing is mandatory even in those with high suspicion and normal peripheral FOXP3 expression.
- Relative cost-effectiveness of using an extensively hydrolyzed casein formula in managing infants with cow's milk allergy in Brazil(2016) GUEST, Julian F.; YANG, Ariana C.; OBA, Jane; RODRIGUES, Maraci; CAETANO, Rosane; POLSTER, LilianObjective: To estimate the cost-effectiveness of three alternative dietetic strategies for cow's milk allergy in Brazil: 1) using an extensively hydrolyzed casein formula (eHCF; -Nutramigen) as a first-line formula, but switching to an amino acid formula (AAF) if infants remain symptomatic; 2) using an AAF as a first-line formula and then switching to an eHCF after 4 weeks once infants are symptom-free, but switching back to an AAF if infants become symptomatic; and 3) using an AAF as a first-line formula and keeping all infants on that formula. The analysis was conducted from the perspective of the Brazilian public health care system, Sistema Unico de Saude. Methods: Decision modeling was used to estimate the probability of immunoglobulin E (IgE)-mediated and non-IgE-mediated allergic infants developing tolerance to cow's milk by 12 months from starting a formula. The models also estimated the Sistema Unico de Saude cost (at 2013/2014 prices) of managing infants over 12 months after starting a formula, as well as the relative cost-effectiveness of each of the dietetic strategies. Results: The probability of developing tolerance to cow's milk by 12 months from starting a formula was higher among infants with either IgE-mediated or non-IgE-mediated allergy who were initially fed with an eHCF, compared with those who were initially fed with an AAF. The total health care cost of initially feeding an eHCF to cow's milk allergic infants was less than that of initially feeding both IgE-mediated and non-IgE-mediated infants with an AAF. Conclusion: Within the study's limitations, using an eHCF instead of an AAF for the first-line management of newly-diagnosed infants with cow's milk allergy affords a cost-effective use of publicly funded resources, since it improves the outcome for less cost.
- Molecular Diagnosis of Shrimp Allergy: Efficiency of Several Allergens to Predict Clinical Reactivity(2015) PASCAL, Mariona; GRISHINA, Galina; YANG, Ariana C.; SANCHEZ-GARCIA, Silvia; LIN, Jing; TOWLE, David; IBANEZ, Maria Dolores; SASTRE, Joaquin; SAMPSON, Hugh A.; AYUSO, RosaliaBACKGROUND: The diagnosis of shellfish allergy remains a challenge for clinicians. Several shellfish allergens have been characterized and their IgE epitopes identified. However, the clinical relevance of this sensitization is still not clear. OBJECTIVE: The objective of this study was to identify allergens and epitopes associated with clinical reactivity to shrimp. METHODS: Shrimp-sensitized subjects were recruited and grouped based on the history of shrimp-allergic reactions and challenge outcome. IgE reactivity to recombinant crustacean allergens, and IgE and IgG4 reactivity to peptides were determined. Subjects sensitized to dust mites and/or cockroach without shrimp sensitization or reported allergic reactions, as well as nonatopic individuals, were used as controls. RESULTS: A total of 86 subjects were recruited with a skin prick test to shrimp; 74 reported shrimp-allergic reactions, 58 were allergic (38 positive double-blind placebo-controlled food challenge and 20 recent anaphylaxis), and 16 were tolerant. All subjects without a history of reactions had negative challenges. The individuals with a positive challenge more frequently recognized tropomyosin and sarcoplasmic calcium-binding proteins than those found tolerant by the challenge. Especially a sarcoplasmic-calcium-binding-protein positive test is very likely to result in a positive challenge, though the frequency of recognition is low. Subjects with dust mite and/or cockroach allergy not sensitized to shrimp recognized arginine kinase and hemocyanin. Several epitopes of these allergens may be important in predicting clinical reactivity. CONCLUSION: Tropomyosin and sarcoplasmic-calciumbinding- protein sensitization is associated with clinical reactivity to shrimp. Myosin light chain testing may help in the diagnosis of clinical reactivity. Arginine kinase and hemocyanin appear to be cross-reacting allergens between shrimp and arthropods. Detection of IgE to these allergens and some of their epitopes may be better diagnostic tools in the routine workup of shrimp allergy. (C) 2015 American Academy of Allergy, Asthma & Immunology
- Fructose biphosphate aldolase: A new cassava allergen(2023) VENTURA, Anne K. R. M.; ALVES, Safiri de P.; CASTRO, Roberta A.; ROSSINI, Bruno C.; DELAZARI, Lucilense S.; OLIVEIRA, Amanda M. de; MORETTI, Ana I. S.; CASTRO, Fabio F. M.; KALIL, Jorge; YANG, Ariana C.; SANTOS, Keity S.Background: Food allergy has considerably increased in recent years and this situation has been aggravated mainly by the consumption of more processed and complex foods, since minor or potentially allergenic foods are not required to be labeled. Manihot esculenta (cassava) is a widely consumed food in South America, Africa, and Asia and can be used in the production of flour and starch, as well as several other products. This root can cause allergic reactions with symptoms ranging from mild to severe. Methods: Thus, the aim of this study was the characterization of the immunogenic cassava proteins responsible for sensitizing patients allergic to it. Using a 2D-SDS-PAGE based proteomic approach, six proteins were identified, including Fructose Bisphosphate Aldolase (FBA). Recom-binant FBA was produced in Expi293 cells and evaluated by immunoblotting with the serum of 10 individual study subjects. Results: Our results showed six cassava IgE-reactive proteins. From those, recombinant fructose bisphosphate aldolase (FBA) showed a positivity of 80% among tested sera, proving to be a highly sensitizing protein. Conclusion: The recombinant FBA molecule obtained in this study can be important for in vivo diagnostic assays, by producing more accurate results, and for desensitization protocols, in which the use of the isolated molecule produces more precise results by avoiding secondary sensitization. Trial registration: All patients signed a consent form approved by the internal ethics committee CAPPesq, Comissao de etica para Analise de Projetos de Pesquisa do HC FMUSP (CAAE: 10420619.6.0000.0068).