KEITY SOUZA SANTOS
Projetos de Pesquisa
Unidades Organizacionais
Departamento de Clínica Médica, Faculdade de Medicina - Docente
LIM/19 - Laboratório de Histocompatibilidade e Imunidade Celular, Hospital das Clínicas, Faculdade de Medicina - Líder
LIM/19 - Laboratório de Histocompatibilidade e Imunidade Celular, Hospital das Clínicas, Faculdade de Medicina - Líder
6 resultados
Resultados de Busca
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conferenceObject Immune Responses Of CVID Patients To COVID-19 Vaccines(2023) MEDEIROS, Giuliana Xavier de; FERREIRA, Loisi de Carvalho Pereira; MAGAWA, Jhosiene Yukari; KURAMOTO, Andreia; SASAHARA, Greyce Luri; FERREIRA, Marcelo; BARROS, Myrthes Maragna Toledo; KALIL, Jorge; MARINHO, Ana Karolina Barreto Berselli; CUNHA-NETO, Edecio; SANTOS, Keity Souza; KOKRON, Cristina- 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 SouzaIntroductionConsidering 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.
- 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, MayanaBackgroundAlthough 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.
- The oldest unvaccinated Covid-19 survivors in South America(2022) V, Mateus de Castro; SILVA, Monize V. R.; NASLAVSKY, Michel S.; SCLIAR, Marilia O.; NUNES, Kelly; PASSOS-BUENO, Maria Rita; CASTELLI, Erick C.; MAGAWA, Jhosiene Y.; ADAMI, Flavia L.; MORETTI, Ana I. S.; OLIVEIRA, Vivian L. de; BOSCARDIN, Silvia B.; CUNHA-NETO, Edecio; KALIL, Jorge; JOUANGUY, Emmanuelle; BASTARD, Paul; CASANOVA, Jean-Laurent; QUINONES-VEGA, Mauricio; SOSA-ACOSTA, Patricia; GUEDES, Jessica S. de; ALMEIDA, Natalia P. de; NOGUEIRA, Fabio C. S.; DOMONT, Gilberto B.; SANTOS, Keity S.; ZATZ, MayanaBackground Although older adults are at a high risk of severe or critical Covid-19, there are many cases of unvaccinated centenarians who had a silent infection or recovered from mild or moderate Covid-19. We studied three Brazilian supercentenarians, older than 110 years, who survived Covid-19 in 2020 before being vaccinated. Results Despite their advanced age, humoral immune response analysis showed that these individuals displayed robust levels of IgG and neutralizing antibodies (NAbs) against SARS-CoV-2. Enrichment of plasma proteins and metabolites related to innate immune response and host defense was also observed. None presented autoantibodies (auto-Abs) to type I interferon (IFN). Furthermore, these supercentenarians do not carry rare variants in genes underlying the known inborn errors of immunity, including particular inborn errors of type I IFN. Conclusion These observations suggest that their Covid-19 resilience might be a combination of their genetic background and their innate and adaptive immunity.
- The oldest unvaccinated Covid-19 survivors in South America (vol 19, 57, 2022)(2022) CASTRO, Mateus V. V. de; SILVA, Monize V. R.; NASLAVSKY, Michel S. S.; SCLIAR, Marilia O. O.; NUNES, Kelly; PASSOS-BUENO, Maria Rita; CASTELLI, Erick C. C.; MAGAWA, Jhosiene Y. Y.; ADAMI, Flavia L.; MORETTI, Ana I. S.; OLIVEIRA, Vivian L. L. de; BOSCARDIN, Silvia B. B.; CUNHA-NETO, Edecio; KALIL, Jorge; JOUANGUY, Emmanuelle; BASTARD, Paul; CASANOVA, Jean-Laurent; QUINONES-VEGA, Mauricio; SOSA-ACOSTA, Patricia; GUEDES, Jessica de S.; ALMEIDA, Natalia P. de; NOGUEIRA, Fabio C. S.; DOMONT, Gilberto B. B.; SANTOS, Keity S. S.; ZATZ, Mayana
- MHC Variants Associated With Symptomatic Versus Asymptomatic SARS-CoV-2 Infection in Highly Exposed Individuals(2021) CASTELLI, Erick C.; V, Mateus de Castro; NASLAVSKY, Michel S.; SCLIAR, Marilia O.; SILVA, Nayane S. B.; ANDRADE, Heloisa S.; SOUZA, Andreia S.; PEREIRA, Raphaela N.; CASTRO, Camila F. B.; MENDES-JUNIOR, Celso T.; MEYER, Diogo; NUNES, Kelly; MATOS, Larissa R. B.; SILVA, Monize V. R.; WANG, Jaqueline Y. T.; ESPOSITO, Joyce; CORIA, Vivian R.; BORTOLIN, Raul H.; HIRATA, Mario H.; MAGAWA, Jhosiene Y.; CUNHA-NETO, Edecio; COELHO, Veronica; SANTOS, Keity S.; MARIN, Maria Lucia C.; KALIL, Jorge; MITNE-NETO, Miguel; MACIEL, Rui M. B.; PASSOS-BUENO, Maria Rita; ZATZ, MayanaDespite the high number of individuals infected by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) who develop coronavirus disease 2019 (COVID-19) symptoms worldwide, many exposed individuals remain asymptomatic and/or uninfected and seronegative. This could be explained by a combination of environmental (exposure), immunological (previous infection), epigenetic, and genetic factors. Aiming to identify genetic factors involved in immune response in symptomatic COVID-19 as compared to asymptomatic exposed individuals, we analyzed 83 Brazilian couples where one individual was infected and symptomatic while the partner remained asymptomatic and serum-negative for at least 6 months despite sharing the same bedroom during the infection. We refer to these as ""discordant couples"". We performed whole-exome sequencing followed by a state-of-the-art method to call genotypes and haplotypes across the highly polymorphic major histocompatibility complex (MHC) region. The discordant partners had comparable ages and genetic ancestry, but women were overrepresented (65%) in the asymptomatic group. In the antigen-presentation pathway, we observed an association between HLA-DRB1 alleles encoding Lys at residue 71 (mostly DRB1*03:01 and DRB1*04:01) and DOB*01:02 with symptomatic infections and HLA-A alleles encoding 144Q/151R with asymptomatic seronegative women. Among the genes related to immune modulation, we detected variants in MICA and MICB associated with symptomatic infections. These variants are related to higher expression of soluble MICA and low expression of MICB. Thus, quantitative differences in these molecules that modulate natural killer (NK) activity could contribute to susceptibility to COVID-19 by downregulating NK cell cytotoxic activity in infected individuals but not in the asymptomatic partners.