KEITY SOUZA SANTOS

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Departamento de Clínica Médica, Faculdade de Medicina - Docente
LIM/19 - Laboratório de Histocompatibilidade e Imunidade Celular, Hospital das Clínicas, Faculdade de Medicina - Líder

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  • article 2 Citação(ões) na Scopus
    IgE and IgG4 Epitopes of Dermatophagoides and Blomia Allergens before and after Sublingual Immunotherapy
    (2023) FIGO, Daniele Danella; MACEDO, Priscilla Rios Cordeiro; GADERMAIER, Gabriele; REMUZGO, Cesar; CASTRO, Fabio Fernandes Morato; KALIL, Jorge; GALVAO, Clovis Eduardo Santos; SANTOS, Keity Souza
    Sublingual immunotherapy (SLIT) is used worldwide to treat house dust mites (HDM) allergy. Epitope specific immunotherapy with peptide vaccines is used far less, but it is of great interest in the treatment of allergic reactions, as it precludes the drawbacks of allergen extracts. The ideal peptide candidates would bind to IgG, blocking IgE-binding. To better elucidate IgE and IgG4 epitope profiles during SLIT, sequences of main allergens, Der p 1, 2, 5, 7, 10, 23 and Blo t 5, 6, 12, 13, were included in a 15-mer peptide microarray and tested against pooled sera from 10 patients pre- and post-1-year SLIT. All allergens were recognized to some extent by at least one antibody isotype and peptide diversity was higher post-1-year SLIT for both antibodies. IgE recognition diversity varied among allergens and timepoints without a clear tendency. Der p 10, a minor allergen in temperate regions, was the molecule with more IgE-peptides and might be a major allergen in populations highly exposed to helminths and cockroaches, such as Brazil. SLIT-induced IgG4 epitopes were directed against several, but not all, IgE-binding regions. We selected a set of peptides that recognized only IgG4 or were able to induce increased ratios of IgG4:IgE after one year of treatment and might be potential targets for vaccines.
  • article 2 Citação(ões) na Scopus
    Is age associated with the development of antibodies against botulinum toxin?
    (2013) AUN, M. V.; CHUNG, T. M.; SANTOS, K. S.; BATTISTELLA, L. M. R.; RIZZO, L. V.; KALIL, J.; GIAVINA-BIANCHI, P.
  • article 14 Citação(ões) na Scopus
    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 Morato
    Scope 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.
  • article 53 Citação(ões) na Scopus
    Sensitization Prevalence, Antibody Cross-Reactivity and Immunogenic Peptide Profile of Api g 2, the Non-Specific Lipid Transfer Protein 1 of Celery
    (2011) GADERMAIER, Gabriele; HAUSER, Michael; EGGER, Matthias; FERRARA, Rosetta; BRIZA, Peter; SANTOS, Keity Souza; ZENNARO, Danila; GIRBL, Tamara; ZUIDMEER-JONGEJAN, Laurian; MARI, Adriano; FERREIRA, Fatima
    Background: Celery (Apium graveolens) represents a relevant allergen source that can elicit severe reactions in the adult population. To investigate the sensitization prevalence and cross-reactivity of Api g 2 from celery stalks in a Mediterranean population and in a mouse model. Methodology: 786 non-randomized subjects from Italy were screened for IgE reactivity to rApi g 2, rArt v 3 (mugwort pollen LTP) and nPru p 3 (peach LTP) using an allergen microarray. Clinical data of 32 selected patients with reactivity to LTP under investigation were evaluated. Specific IgE titers and cross-inhibitions were performed in ELISA and allergen microarray. Balb/c mice were immunized with purified LTPs; IgG titers were determined in ELISA and mediator release was examined using RBL-2H3 cells. Simulated endolysosomal digestion was performed using microsomes obtained from human DCs. Results: IgE testing showed a sensitization prevalence of 25.6% to Api g 2, 18.6% to Art v 3, and 28.6% to Pru p 3 and frequent co-sensitization and correlating IgE-reactivity was observed. 10/32 patients suffering from LTP-related allergy reported symptoms upon consumption of celery stalks which mainly presented as OAS. Considerable IgE cross-reactivity was observed between Api g 2, Art v 3, and Pru p 3 with varying inhibition degrees of individual patients' sera. Simulating LTP mono-sensitization in a mouse model showed development of more congruent antibody specificities between Api g 2 and Art v 3. Notably, biologically relevant murine IgE cross-reactivity was restricted to the latter and diverse from Pru p 3 epitopes. Endolysosomal processing of LTP showed generation of similar clusters, which presumably represent T-cell peptides. Conclusions: Api g 2 represents a relevant celery stalk allergen in the LTP-sensitized population. The molecule displays common B cell epitopes and endolysosomal peptides that encompass T cell epitopes with pollen and plant-food derived LTP.
  • article 18 Citação(ões) na Scopus
    Proteomic Analysis of Urine in Rats Chronically Exposed to Fluoride
    (2011) KOBAYASHI, Claudia Ayumi Nakai; LEITE, Aline de Lima; SILVA, Thelma Lopes da; SANTOS, Lucilene Delazari dos; NOGUEIRA, Fabio Cesar Sousa; SANTOS, Keity Souza; OLIVEIRA, Rodrigo Cardoso de; PALMA, Mario Sergio; DOMONT, Gilberto Barbosa; BUZALAF, Marilia Afonso Rabelo
    Urine is an ideal source of materials to search for potential disease-related biomarkers as it is produced by the affected tissues and can be easily obtained by noninvasive methods. 2-DE-based proteomic approach was used to better understand the molecular mechanisms of injury induced by fluoride (F-) and define potential biomarkers of dental fluorosis. Three groups of weanling male Wistar rats were treated with drinking water containing 0 (control), 5, or 50 ppm F- for 60 days (n = 15/group). During the experimental period, the animals were kept individually in metabolic cages, to analyze the water and food consumption, as well as fecal and urinary F excretion. Urinary proteome profiles were examined using 2-DE and Colloidal Coomassie Brilliant Blue staining. A dose-response regarding F- intake and excretion was detected. Quantitative intensity analysis revealed 8, 11, and 8 significantly altered proteins between control vs. 5 ppm F-, control vs. 50 ppm F- and 5 ppm F- vs. 50 ppm F- groups, respectively. Two proteins regulated by androgens (androgen-regulated 20-KDa protein and 0c-2,1-globulin) and one related to detoxification (aflatoxin-Bl-aldehyde-reductase) were identified by MALDI-TOF-TOF MS/MS. Thus, proteomic analysis can help to better understand the mechanisms underlying F- toxicity, even in low doses. 2010 Wiley Periodicals, Inc. J Biochem Mol Toxicol 25:8-14, 2011; View this article online at wileyonlinelibrary.com. DOI 10:1002/jbt.20353
  • article 5 Citação(ões) na Scopus
    Immunodominant antibody responses directed to SARS-CoV-2 hotspot mutation sites and risk of immune escape
    (2023) OLIVEIRA, Jamille Ramos; RUIZ, Cesar Manuel Remuzgo; MACHADO, Rafael Rahal Guaragna; MAGAWA, Jhosiene Yukari; DAHER, Isabela Pazotti; URBANSKI, Alysson Henrique; SCHMITZ, Gabriela Justamante Haendel; ARCURI, Helen Andrade; FERREIRA, Marcelo Alves; SASAHARA, Greyce Luri; MEDEIROS, Giuliana Xavier de; JR, Roberto Carlos Vieira Silva; DURIGON, Edison Luiz; BOSCARDIN, Silvia Beatriz; ROSA, Daniela Santoro; SCHECHTMAN, Deborah; NAKAYA, Helder. I. I.; CUNHA-NETO, Edecio; GADERMAIER, Gabriele; KALIL, Jorge; COELHO, Veronica; SANTOS, Keity Souza
    IntroductionConsidering the likely need for the development of novel effective vaccines adapted to emerging relevant CoV-2 variants, the increasing knowledge of epitope recognition profile among convalescents and afterwards vaccinated with identification of immunodominant regions may provide important information. MethodsWe used an RBD peptide microarray to identify IgG and IgA binding regions in serum of 71 COVID-19 convalescents and 18 vaccinated individuals. ResultsWe found a set of immunodominant RBD antibody epitopes, each recognized by more than 30% of the tested cohort, that differ among the two different groups and are within conserved regions among betacoronavirus. Of those, only one peptide, P44 (S415-429), recognized by 68% of convalescents, presented IgG and IgA antibody reactivity that positively correlated with nAb titers, suggesting that this is a relevant RBD region and a potential target of IgG/IgA neutralizing activity. DiscussionThis peptide is localized within the area of contact with ACE-2 and harbors the mutation hotspot site K417 present in gamma (K417T), beta (K417N), and omicron (K417N) variants of concern. The epitope profile of vaccinated individuals differed from convalescents, with a more diverse repertoire of immunodominant peptides, recognized by more than 30% of the cohort. Noteworthy, immunodominant regions of recognition by vaccinated coincide with mutation sites at Omicron BA.1, an important variant emerging after massive vaccination. Together, our data show that immune pressure induced by dominant antibody responses may favor hotspot mutation sites and the selection of variants capable of evading humoral response.
  • article 0 Citação(ões) na Scopus
    Follow-up of young adult monozygotic twins after simultaneous critical coronavirus disease 2019: a case report (vol 9, 1008585, 2022)
    (2023) CASTRO, Mateus V. de; SILVA, Monize V. R.; SOARES, Flavia B.; CORIA, Vivian R.; NASLAVSKY, Michel S.; SCLIAR, Marilia O.; CASTELLI, Erick C.; OLIVEIRA, Jamile R. de; MEDEIROS, Giuliana X. de; SASAHARA, Greyce L.; SANTOS, Keity S.; CUNHA-NETO, Edecio; KALIL, Jorge; ZATZ, Mayana
  • article 0 Citação(ões) na Scopus
    Follow-up of young adult monozygotic twins after simultaneous critical coronavirus disease 2019: A case report
    (2022) V, Mateus de Castro; SILVA, Monize V. R.; SOARES, Flavia B.; CORIA, Vivian R.; NASLAVSKY, Michel S.; SCLIAR, Marilia O.; CASTELLI, Erick C.; OLIVEIRA, Jamile R. de; SASAHARA, Greyce L.; SANTOS, Keity S.; CUNHA-NETO, Edecio; KALIL, Jorge; ZATZ, Mayana
    BackgroundThe influence of the host genome on coronavirus disease 2019 (COVID-19) susceptibility and severity is supported by reports on monozygotic (MZ) twins where both were infected simultaneously with similar disease outcomes, including several who died due to the SARS-CoV-2 infection within days apart. However, successive exposures to pathogens throughout life along with other environmental factors make the immune response unique for each individual, even among MZ twins. Case presentation and methodsHere we report a case of a young adult monozygotic twin pair, who caught attention since both presented simultaneously severe COVID-19 with the need for oxygen support despite age and good health conditions. One of the twins, who spent more time hospitalized, reported symptoms of long-COVID even 7 months after infection. Immune cell profile and specific responses to SARS-CoV-2 were evaluated as well as whole exome sequencing. ConclusionAlthough the MZ twin brothers shared the same genetic mutations which may be associated with their increased risk of developing severe COVID-19, their clinical progression was different, reinforcing the role of both immune response and genetics in the COVID-19 presentation and course. Besides, post-COVID syndrome was observed in one of them, corroborating an association between the duration of hospitalization and the occurrence of long-COVID symptoms.
  • article 8 Citação(ões) na Scopus
    MUC22, HLA-A, and HLA-DOB variants and COVID-19 in resilient super-agers from Brazil
    (2022) CASTELLI, Erick C.; CASTRO, Mateus V. de; NASLAVSKY, Michel S.; SCLIAR, Marilia O.; SILVA, Nayane S. B.; PEREIRA, Raphaela N.; CIRIACO, Viviane A. O.; CASTRO, Camila F. B.; MENDES-JUNIOR, Celso T.; SILVEIRA, Etiele de S.; OLIVEIRA, Iuri M. de; ANTONIO, Eduardo C.; VIEIRA, Gustavo F.; MEYER, Diogo; NUNES, Kelly; MATOS, Larissa R. B.; SILVA, Monize V. R.; WANG, Jaqueline Y. T.; ESPOSITO, Joyce; CORIA, Vivian R.; MAGAWA, Jhosiene Y.; SANTOS, Keity S.; CUNHA-NETO, Edecio; KALIL, Jorge; BORTOLIN, Raul H.; HIRATA, Mario Hiroyuki; DELL'AQUILA, Luiz P.; RAZUK-FILHO, Alvaro; BATISTA-JUNIOR, Pedro B.; DUARTE-NETO, Amaro N.; DOLHNIKOFF, Marisa; SALDIVA, Paulo H. N.; PASSOS-BUENO, Maria Rita; ZATZ, Mayana
    BackgroundAlthough aging correlates with a worse prognosis for Covid-19, super elderly still unvaccinated individuals presenting mild or no symptoms have been reported worldwide. Most of the reported genetic variants responsible for increased disease susceptibility are associated with immune response, involving type I IFN immunity and modulation; HLA cluster genes; inflammasome activation; genes of interleukins; and chemokines receptors. On the other hand, little is known about the resistance mechanisms against SARS-CoV-2 infection. Here, we addressed polymorphisms in the MHC region associated with Covid-19 outcome in super elderly resilient patients as compared to younger patients with a severe outcome. MethodsSARS-CoV-2 infection was confirmed by RT-PCR test. Aiming to identify candidate genes associated with host resistance, we investigated 87 individuals older than 90 years who recovered from Covid-19 with mild symptoms or who remained asymptomatic following positive test for SARS-CoV-2 as compared to 55 individuals younger than 60 years who had a severe disease or died due to Covid-19, as well as to the general elderly population from the same city. Whole-exome sequencing and an in-depth analysis of the MHC region was performed. All samples were collected in early 2020 and before the local vaccination programs started. ResultsWe found that the resilient super elderly group displayed a higher frequency of some missense variants in the MUC22 gene (a member of the mucins' family) as one of the strongest signals in the MHC region as compared to the severe Covid-19 group and the general elderly control population. For example, the missense variant rs62399430 at MUC22 is two times more frequent among the resilient super elderly (p = 0.00002, OR = 2.24). ConclusionSince the pro-inflammatory basal state in the elderly may enhance the susceptibility to severe Covid-19, we hypothesized that MUC22 might play an important protective role against severe Covid-19, by reducing overactive immune responses in the senior population.
  • article 0 Citação(ões) na Scopus
    Immunological evaluation of young unvaccinated patients with Turner syndrome after COVID-19
    (2023) CASTRO, Mateus V. de; SILVA, Monize V. R.; OLIVEIRA, Luana de M.; GOZZI-SILVA, Sarah C.; NASLAVSKY, Michel S.; SCLIAR, Marilia O.; MAGALHAES, Monize L.; ROCHA, Katia M. da; NUNES, Kelly; CASTELLI, Erick C.; MAGAWA, Jhosiene Y.; SANTOS, Keity S.; CUNHA-NETO, Edecio; SATO, Maria N.; ZATZ, Mayana
    Objectives: The X-chromosome contains the largest number of immune-related genes, which play a major role in COVID-19 symptomatology and susceptibility. Here, we had a unique opportunity to investigate, for the first time, COVID-19 outcomes in six unvaccinated young Brazilian patients with Turner syndrome (TS; 45, X0), including one case of critical illness in a child aged 10 years, to evaluate their immune response according to their genetic profile. Methods: A serological analysis of humoral immune response against SARS-CoV-2, phenotypic character-ization of antiviral responses in peripheral blood mononuclear cells after stimuli, and the production of cytotoxic cytokines of T lymphocytes and natural killer cells were performed in blood samples collected from the patients with TS during the convalescence period. Whole exome sequencing was also performed.Results: Our volunteers with TS showed a delayed or insufficient humoral immune response to SARS-CoV-2 (particularly immunoglobulin G) and a decrease in interferon-gamma production by cluster of differentiation (CD)4 + and CD8 + T lymphocytes after stimulation with toll-like receptors 7/8 agonists. In contrast, we observed a higher cytotoxic activity in the volunteers with TS than the volunteers without TS after phor-bol myristate acetate/ionomycin stimulation, particularly granzyme B and perforin by CD8 + and natural killer cells. Interestingly, two volunteers with TS carry rare genetic variants in genes that regulate type I and III interferon immunity.Conclusion: Following previous reports in the literature for other conditions, our data showed that pa-tients with TS may have an impaired immune response against SARS-CoV-2. Furthermore, other medical conditions associated with TS could make them more vulnerable to COVID-19.(c) 2023 The Author(s).