ANA KAROLINA BARRETO BERSELLI MARINHO
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
4 resultados
Resultados de Busca
Agora exibindo 1 - 4 de 4
- 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.
- 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.
- 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.