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
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conferenceObject FREQUENCY OF LYMPHOMAS IN A COHORT OF PATIENTS WITH COMMON VARIABLE IMMUNODEFICIENCY(2013) SINI, B. C.; KOKRON, C. M.; LEVY, D.; PEREIRA, Juliana; OLIVEIRA, Ana Karolina Barreto; COHON, Andrea; KALIL, Jorge; BYDLOWSKI, S. P.; BARROS, Myrthes ToledoIntroduction: Common variable immunodeficiency (CVID) is characterized by recurrent infections and in-creased susceptibility to autoimmunity and malignancies. Objective: To evaluate the frequency of lymphoma in a cohort of patients with CVID. Methods: Analysis of data obtained from medical records. Results: We analyzed 144 patients, 80 men and 64 women, aged 15-72 years. Seven (0.5 %) lymphoma cases were diagnosed (1 Hodgkin lymphoma and 6 non-Hodgkin lymphomas), affecting 5 men and 2 women aged 1953 years at lymphoma diagnosis. The time period between the onset of symptoms of CVID and lymphoma diagnosis ranged from 7 to 24 years in 4 patients and in 3 of them the diagnosis of both diseases were nearly overlapped preceding the CVID diagnosis in only 1, 3 and 6 months. Fever, splenomegaly and lymphadenopathy occurred in all patients. Lymphocytosis with inversion of the CD4/CD8 ratio at the expense of increased CD8+ T cells was detected in 2 patients and lymphopenia in one. B lymphocytes were undetectable in 3 patients in whom the diagnosis of lymphoma and CVID were established simultaneously and in one B cells were present at the beginning of CVID but undetectable at diagnosis of lymphoma. Conclusions: Patients with absence of B cells in recently diagnosed CVID or absence of B cells in long term followed CVID with previously detectable B cells demands a screening for the presence of lymphomas.- 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.
- Can patients with common variable immunodeficiency have allergic rhinitis?(2013) AGONDI, Rosana C.; BARROS, Myrthes T.; KOKRON, Cristina M.; COHON, Andrea; OLIVEIRA, Ana K. B.; KALIL, Jorge; GIAVINA-BIANCHI, PedroBackground: Rhinosinusitis is highly prevalent in patients with common variable immunodeficiency (CVID), and probably allergic rhinitis (AR) may be masked by a history of repeated respiratory infections. The diagnosis of AR is based on the patient's symptoms and detection of specific immunoglobulin E (IgE) to aeroallergens. This study was designed to identify rhinitis of probable allergic cause in patients with CVID. Methods: This study included 72 adult CVID patients. The patients were divided into three groups according to their history: suggestive of AR, nonallergic rhinitis, and without rhinitis. They were tested for total and specific IgE (in vivo and in vitro). Results: The patients' mean age was 38.2 years. A history of chronic rhinitis was observed in 59 (81.9%) of the cases, 31 of which (43%) had a history suggestive of AR. Patients with a history of rhinitis (whether allergic or nonallergic) presented an earlier onset of symptoms and diagnosis of CVID. Total IgE was undetectable in 86.1% of patients. AR was confirmed by detection of specific IgE to aeroallergens in only 5.6% of the patients. Conclusion: In CVID patients, chronic rhinitis may be allergic, because many have personal and family histories suggestive of atopy. However, in this study, allergy was confirmed by specific IgE detection in only 5.6% of cases. CVID patients with a history suggestive of AR commonly present negative results on traditional testing, so additional experiments may be necessary. One suggestion for the investigation of AR in CVID patients would be nasal provocation with the most prevalent allergens.
- 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.
conferenceObject CASE REPORT: LEPROSY ASSOCIATED TO COMMON VARIABLE IMMUNODEFICIENCY(2013) BARROS, Myrthes Toledo; TRINDADE, M. B.; SINI, B. C.; OLIVEIRA, Ana Karolina Barreto; SANCHEZ, J. A.; KALIL, Jorge; KOKRON, C. M.Introduction: Common variable immunodeficiency (CVID) is characterized by recurrent infections and, less often, opportunistic infections. Objective: To report a patient with CVID and leprosy. Case: White male, 25 years, with CVID diagnostic established 2 ½ years before, under IGIV monthly replacement. Two years after the diagnosis of CVID, he reported recent appearance of hypopigmented anesthetic spots in the upper limbs and trunk. Skin biopsy: lymphocytic inflammatory infiltrate with sketches of perivascular and perianexial granulomas attacking nerve fibers in the middle and deep dermis. The bacterial index, the tuberculin skin test and research for HIV were negative. The diagnosis of borderline tuberculoid leprosy was established. The number of TCD4+ cells was lower before (572 cells/mm 3) than after (665 cells/mm 3) skin lesions detection. We found no previous reports in the literature of leprosy associated to CVID. Conclusion: We speculate if in this CVID patient the skin lesions corresponded to inflammatory immune reconstitution syndrome (IRIS) associated to leprosy andif IGIVreplacement could modified the outcome of a previous infection by M. leprae.- Primary Immunodeficiency Diseases in Different Age Groups: A Report on 1,008 Cases from a Single Brazilian Reference Center(2013) CARNEIRO-SAMPAIO, Magda; MORAES-VASCONCELOS, Dewton; KOKRON, Cristina M.; JACOB, Cristina M. A.; TOLEDO-BARROS, Myrthes; DORNA, Mayra B.; WATANABE, Leticia A.; MARINHO, Ana Karolina B. B.; CASTRO, Ana Paula Moschione; PASTORINO, Antonio C.; SILVA, Clovis Artur A.; FERREIRA, Mauricio D.; RIZZO, Luiz V.; KALIL, Jorge E.; DUARTE, Alberto J. S.Primary immunodeficiencies (PIDs) represent a large group of diseases that affect all age groups. Although PIDs have been recognized as rare diseases, there is epidemiological evidence suggesting that their real prevalence has been underestimated. We performed an evaluation of a series of 1,008 infants, children, adolescents and adults with well-defined PIDs from a single Brazilian center, regarding age at diagnosis, gender and PID category according to the International Union of Immunological Societies classification. Antibody deficiencies were the most common category in the whole series (61 %) for all age groups, with the exception of <2-year-old patients (only 15 %). In the >30-year-old group, antibody deficiencies comprised 84 % of the diagnoses, mostly consisting of common variable immunodeficiency, IgA deficiency and IgM deficiency. Combined immunodeficiencies represented the most frequent category in <2-years-old patients. Most congenital defects of phagocytes were identified in patients <5 -years of age, as were the diseases of immune dysregulation, with the exception of APECED. DiGeorge syndrome and ataxia-telangiectasia were the most frequent entities in the category of well-defined syndromes, which were mostly identified in patients <10-years of age. Males represented three-quarters and two-thirds of <2 -years-old and 2-5-years -old patients, respectively, whereas females predominated among the >30-year-old patients. Our data indicated that some PIDs were only detected at early ages, likely because affected patients do not survive long. In addition, our data pointed out that different strategies should be used to search for PIDs in infants and young children as compared to older patients.
conferenceObject Evaluation of B lymphocyte Profile from Common Variable Immunodeficiency Patients Before and After Immunization with Antigens(2013) BALDASSIN, M. P. M.; OLIVEIRA, A. K. B.; BARROS, M. T.; COHON, A.; KALIL, J.; KOKRON, M.