CRISTINA MARIA KOKRON
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
6 resultados
Resultados de Busca
Agora exibindo 1 - 6 de 6
- Dysregulated CD1 profile in myeloid dendritic cells in CVID is normalized by IVIg treatment(2013) PAQUIN-PROULX, Dominic; SANTOS, Bianca A. N.; CARVALHO, Karina I.; TOLEDO-BARROS, Myrthes; OLIVEIRA, Ana Karolina Barreto de; KOKRON, Cristina M.; KALIL, Jorge; MOLL, Markus; KALLAS, Esper G.; SANDBERG, Johan K.
- Oral manifestations in patients with hypogammaglobulinemia(2012) FERNANDES, Karin Sa; KOKRON, Cristina Maria; BARROS, Myrthes Toledo; KALIL, Jorge; GALLOTTINI, MarinaObjective. The overall objective of this study was to assess the oral manifestations and their association with immunologic status and health history, of individuals with hypogammaglobulinemia. Study Design. A case-controlled study of 100 subjects with hypogammaglobulinemia and 93 control individuals was performed. All participants were examined for dental caries, periodontal disease, mucosal lesions/infections, and general oral health problems. Decayed, missing, filled teeth and community periodontal index were recorded. Complete blood count, serum immunoglobulins, and lymphocyte immunophenotyping were measured on the same day of the oral health assessment. Results. Individuals with hypogammaglobulinemia showed higher prevalence of enamel hypoplasia and complaints of dry mouth, and lower prevalence of dental caries and periodontal disease. Conclusions. The systemic conditions associated with hypogammaglobulinemia were not associated with enhanced susceptibility to caries, gingivitis, or periodontitis; however, individuals with hypogammaglobulinemia were more likely to report more episodes of recurrent aphthous ulcers compared with control individuals. (Oral Surg Oral Med Oral Pathol Oral Radiol 2012;114:e19-e24)
- IVIg Immune Reconstitution Treatment Alleviates the State of Persistent Immune Activation and Suppressed CD4 T Cell Counts in CVID(2013) PAQUIN-PROULX, Dominic; SANTOS, Bianca A. N.; CARVALHO, Karina I.; TOLEDO-BARROS, Myrthes; OLIVEIRA, Ana Karolina Barreto de; KOKRON, Cristina M.; KALIL, Jorge; MOLL, Markus; KALLAS, Esper G.; SANDBERG, Johan K.Common variable immunodeficiency (CVID) is characterized by defective B cell function, impaired antibody production, and increased susceptibility to bacterial infections. Here, we addressed the hypothesis that poor antibody-mediated immune control of infections may result in substantial perturbations in the T cell compartment. Newly diagnosed CVID patients were sampled before, and 6-12 months after, initiation of intravenous immunoglobulin (IVIg) therapy. Treatment-naive CVID patients displayed suppressed CD4 T cell counts and myeloid dendritic cell (mDC) levels, as well as high levels of immune activation in CD8 T cells, CD4 T cells, and invariant natural killer T (iNKT) cells. Expression of co-stimulatory receptors CD80 and CD83 was elevated in mDCs and correlated with T cell activation. Levels of both FoxP3+ T regulatory (Treg) cells and iNKT cells were low, whereas soluble CD14 (sCD14), indicative of monocyte activation, was elevated. Importantly, immune reconstitution treatment with IVIg partially restored the CD4 T cell and mDC compartments. Treatment furthermore reduced the levels of CD8 T cell activation and mDC activation, whereas levels of Treg cells and iNKT cells remained low. Thus, primary deficiency in humoral immunity with impaired control of microbial infections is associated with significant pathological changes in cell-mediated immunity. Furthermore, therapeutic enhancement of humoral immunity with IVIg infusions alleviates several of these defects, indicating a relationship between poor antibody-mediated immune control of infections and the occurrence of abnormalities in the T cell and mDC compartments. These findings help our understanding of the immunopathogenesis of primary immunodeficiency, as well as acquired immunodeficiency caused by HIV-1 infection.
- Outcome of SARS-CoV-2 Infection in 121 Patients with Inborn Errors of Immunity: A Cross-Sectional Study(2021) GOUDOURIS, Ekaterini Simoes; PINTO-MARIZ, Fernanda; MENDONCA, Leonardo Oliveira; ARANDA, Carolina Sanchez; GUIMARAES, Rafaela Rolla; KOKRON, Cristina; BARROS, Myrthes Toledo; ANISIO, Flavia; ALONSO, Maria Luiza Oliva; MARCELINO, Fernanda; VALLE, Solange Oliveira Rodrigues; DORTAS JUNIOR, Sergio; BARRETO, Irma Douglas Paes; FERREIRA, Janaira Fernandes Severo; ROXO-JUNIOR, Persio; SILVA, Almerinda Maria do Rego; CAMPINHOS, Fernanda Lugao; BONFIM, Carmem; LOTH, Gisele; FERNANDES, Juliana Folloni; GARCIA, Julia Lopes; CAPELO, Albertina; TAKANO, Olga Akiko; NADAF, Maria Isabel Valdomir; TOLEDO, Eliana C.; CUNHA, Luciana Araujo Oliveira; GESU, Regina Sumiko Watanabe Di; SCHIDLOWSKI, Laire; FILLIPO, Priscila; BICHUETTI-SILVA, Danielli C.; SOLDATELI, Gustavo; FERRARONI, Natasha Reboucas; DANTAS, Ellen de Oliveira; PESTANA, Simone; MANSOUR, Eli; ULAF, Raisa Gusso; PRANDO, Carolina; CONDINO-NETO, Antonio; GRUMACH, Anete SevciovicPurpose There is still scarce data on SARS-CoV-2 infection in patients with Inborn Errors of Immunity (IEI) and many unresolved questions. We aimed to describe the clinical outcome of SARS-CoV-2 infection in Brazilian IEI patients and identify factors influencing the infection. Methods We did a cross-sectional, multicenter study that included patients of any age affected by IEI and SARS-CoV-2 infection. The variables studied were sex, age, type of IEI, comorbidities (number and type), treatment in use for IEI, clinical manifestations and severity of SARS-CoV-2 infection. Results 121 patients were included: 55.4% female, ages from six months to 74 yo (median age = 25.1 yo). Most patients had predominantly antibody deficiency (n = 53). The infection was mostly asymptomatic (n = 21) and mild (n = 66), and one child had multisystem inflammatory syndrome (MIS-C). We could not observe sex-related susceptibility, and there was a weak correlation between age and severity of infection. The number of comorbidities was higher in severe cases, particularly bronchiectasis and cardiopathy. There were no severe cases in hereditary angioedema patients. Six patients aged 2 to 74 years died, three of them with antibody deficiency. Conclusion The outcome was mild in most patients, but the Case Fatality Ratio was higher than in the general population. However, the type of IEI was not a determining factor for severity, except for complement deficiencies linked to milder COVID-19. The severity of SARS-CoV-2 infection seems to be more related to older age, a higher number of comorbidities and type of comorbidities (bronchiectasis and cardiopathy).
- Bone Mineral Density is Related to CD4+ T Cell Counts and Muscle Mass is Associated with B Cells in Common Variable Immunodeficiency Patients(2024) MELO, Daniel Barreto de; PEREIRA, Rosa Maria Rodrigues; SINI, Bruno; LEVY, Debora; TAKAYAMA, Lilian; KOKRON, Cristina Maria; MARINHO, Ana Karolina Berselli; GRECCO, Octavio; KALIL FILHO, Jorge Elias; BARROS, Myrthes ToledoBackground: Common variable immunodeficiency (CVID) is a primary immunodeficiency characterized by chronic/recurrent respiratory infections, bronchiectasis, autoimmunity, inflammatory, gastrointestinal diseases and malignancies associated with a chronic inflammatory state and increased risk of osteoporosis and muscle loss. Aim: The aim of this study was to evaluate bone mineral density (BMD), body composition and their relationship with lymphocyte subpopulations in CVID patients. Methods: Dual-energy X-ray absorptiometry was performed to assess BMD, lean mass, and fat mass in CVID patients. Peripheral blood CD4(+), CD8(+), and CD19(+) cells were measured using flow cytometry. Results: Thirty-three patients (37.3 +/- 10.8 years old) were examined. Although only 11.8% of the individuals were malnourished (BMI <18.5 kg/m(2)), 27.7% of them had low skeletal muscle mass index (SMI), and 57.6% of them had low BMD. Patients with osteopenia/osteoporosis presented lower weight (p = 0.007), lean mass (p = 0.011), appendicular lean mass (p = 0.011), SMI (p = 0.017), and CD4+ count (p = 0.030). Regression models showed a positive association between CD4+ count and bone/muscle parameters, whereas CD19+ B cell count was only associated with muscle variables. Analysis of ROC curves indicated a cutoff value of CD4+ count (657 cells/mm3; AUC: 0.71, 95% CI 0.52-0.90) which was related to low BMD. Weight (p = 0.004), lean mass (p = 0.027), appendicular lean mass (p = 0.022), SMI (p = 0.029), total bone mineral content (p = 0.005), lumbar (p = 0.005), femoral neck (p = 0.035), and total hip BMD (p<0.001) were found to be lower in patients with CD4+ count below the cutoff. Conclusion: CVID patients presented with low BMD, which was associated with CD4+ count. Moreover, low muscle parameters were correlated with B cell count.
- Inversion of the V delta 1 to V delta 2 gamma delta T cell ratio in CVID is not restored by IVIg and is associated with immune activation and exhaustion(2016) PAQUIN-PROULX, Dominic; BARSOTTI, Nathalia Silveira; SANTOS, Bianca A. N.; MARINHO, Ana Karolina B. B.; KOKRON, Cristina M.; CARVALHO, Karina I.; BARROS, Myrthes T.; KALIL, Jorge; NIXON, Douglas F.; KALLAS, Esper G.Common variable immunodeficiency (CVID) is defined by low levels of IgG and IgA, but perturbations in T cells are also commonly found. However, there is limited information on gamma delta T cells in CVID patients. Newly diagnosed CVID patients (n=15) were enrolled before and after intravenous IgG (IVIg) replacement therapy. Cryopreserved peripheral blood mononuclear cells were then used to study gamma delta T cells and CVID patients were compared to healthy controls (n=22). The frequency and absolute count of V delta 1 gamma delta T cells was found to be increased in CVID (median 0.60% vs 2.64%, P<0.01 and 7.5 vs 39, P<0.01 respectively), while they were decreased for V delta 2 gamma delta T cells (median, 2.36% vs 0.74%, P<0.01 and 37.8 vs 13.9, P<0.01 respectively) resulting in an inversion of the V delta 1 to V delta 2 ratio (0.24 vs 1.4, P<0.001). Markers of immune activation were elevated on all subsets of gamma delta T cells, and HLA-DR expression was associated with an expansion of V delta 1 gamma delta T cells (r=0.73, P=0.003). Elevated PD-1 expression was found only on V delta 2 gamma delta T cells (median 1.15% vs 3.08%, P<0.001) and was associated with the decrease of V delta 2 gamma delta T cells (r=-0.67, P=0.007). IVIg had no effect on the frequency of V delta 1 and V delta 2 gamma delta T cells or HLA-DR expression, but alleviated CD38 expression on V delta 1 gamma delta T cells (median MFI 965 vs 736, P<0.05). These findings suggest that immunological perturbations of gamma delta T cells are a general feature associated with CVID and are only partially reversed by IVIg therapy.