CRISTINA MIUKI ABE JACOB
Projetos de Pesquisa
Unidades Organizacionais
LIM/36 - Laboratório de Pediatria Clínica, Hospital das Clínicas, Faculdade de Medicina - Líder
51 resultados
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conferenceObject Novel Mutations in MVK Associated with Hyperimmunoglobulinemia D with Periodic Fever Syndrome Phenotype(2014) VASCONCELOS, D. Moraes; FUJIHIRA, E.; OLIVEIRA, J. B.; JESUS, A. A.; SILVA, C.; CASTRO, A. P. M.; DORNA, M. B.; WATANABE, L.; PONTILLO, A.; CHUFFI-BARROS, N.; JACOB, C. M. A.; CARNEIRO-SAMPAIO, M. M. S.; DUARTE, A. J.conferenceObject The Extended Clinical Phenotype of 36 Patients with Chronic Mucocutaneous Candidiasis Due to Gain-of-Function Mutations in STAT1(2014) FREDE, N.; DEPNER, M.; RAABE, J.; DOFFINGER, R.; GKRANIA-KLOTSAS, E.; KUMARARATNE, D.; ATKINSON, T. P.; SCHROEDER, H. W.; NIEHUES, T.; DUECKERS, G.; PUCK, J.; EISENSTEIN, E. M.; STRAY-PEDERSEN, A.; BAUMANN, U.; SCHMIDT, R. E.; FRANCO, J. L.; ORREGO, J. C.; BEN-SHOSHAN, M.; MCCUSKER, C.; JACOB, C. M.; CARNEIRO-SAMPAIO, M.; DEVLIN, L. A.; EDGAR, J. D.; HENDERSON, P.; DYRSO, T.; SENEVIRATNE, S. L.; WANDERS, J.; STAUSS, H.; MEYTS, I.; MOENS, L.; JESENAK, M.; GRIMBACHER, B.- Chronic autoimmune urticaria as the first manifestation of juvenile systemic lupus erythematosus(2011) SPADONI, M. S.; JACOB, C. M. A.; AIKAWA, N. E.; JESUS, A. A.; FOMIN, A. B.; SILVA, C. A.Chronic urticaria (daily or almost daily symptoms lasting for more than six weeks) is characterized by wheals and erythema, with or without itching. A few case reports have shown chronic autoimmune urticaria at the beginning of systemic lupus erythematosus (SLE), particularly in adults. However, the prevalence of this manifestation in a lupus paediatric population was not studied. During 27 consecutive years, 5419 patients were followed up at our University Hospital and 271 (5%) had juvenile SLE (American College of Rheumatology criteria). Two of them (0.7%) had chronic and painless autoimmune urticaria as the first manifestation of juvenile SLE, and were reported herein. One case was a five-year old female with continuous widespread urticaria (duration 120 days), antinuclear antibodies (ANA) 1:640 (dense fine speckled pattern) and elevated complement levels. The juvenile SLE diagnosis was established after one year. The other case was a 13-year old female who had chronic widespread urticaria (lasting 45 days), ANA 1:160 (fine speckled pattern) and normal complement levels. The juvenile SLE diagnosis was established after three years. In conclusion, chronic autoimmune urticaria is very rare and may be the first lupus manifestation, particularly associated with the presence of autoantibodies. This study reinforces the importance of a rigorous follow-up in children and adolescents suffering from autoimmune urticaria due to the possibility of connective tissue disorders, such as paediatric lupus. Lupus (2011) 20, 763-766.
- Serum lipids in Brazilian children and adolescents: determining their reference intervals(2015) SLHESSARENKO, Natasha; JACOB, Cristina M. A.; AZEVEDO, Raymundo S.; FONTES, Cor J. F.; NOVAK, Glaucia V.; ANDRIOLO, AdagmarBackground: Demographic, geographic, environmental and genetic factors influence lipids. In many countries, the normal lipid ranges for laboratory tests are based on references from American children and adolescents. In this work, we determined the reference intervals (RIs) for total cholesterol (TC), high-density lipoprotein cholesterol (HDL-c), non-high-density lipoprotein cholesterol (nHDL-c), low-density lipoprotein cholesterol (LDL-c) and triglycerides (TG) in Brazilian healthy children and adolescents. Methods: A cross-sectional study was conducted of 1,866 randomly sampled healthy children and adolescents from kindergartens and schools. Blood samples were collected after a variable period of fasting based on the age of the participant. The upper cut-off points were the 75th and 95th percentiles for TC, nHDL-c, LDL-c and TG. The 10th percentile (low) was used as the bottom level for HDL-c. Non-parametric tests were used for statistical analyses. Results: The following RI and 75th and 95th percentiles were observed for each age interval. The 95th percentile values obtained for TC were: 1 to 2 years, 189 mg/dL, 3 to 8 years, 199 mg/dL; 9 to 12 years, 205 mg/dL. For the nHDL c, the only age group 1 to 12 years, this percentile value was 150 mg/dL. For the LDL-cholesterol, the values corresponding to the percentiles above, aged 1 to 8 years and 9 to 12 years, were 132 mg/dL 139 mg/dL, respectively. For the triglycerides, the values corresponding to 95th percentile were: 1 year, 189 mg/dL; 2 to 5 years, 139 mg/dL; 6 to 12 years, 139 mg/dL. The 10th percentiles for HDL-c were 24 mg/dL, 28 mg/dL, 32 mg/dL and 36 mg/dL for children 1, 2, 3 and 4-12 years old, respectively. Conclusions: The lipid reference intervals defined in the studied Brazilian children and adolescents differ from those recommended by the international literature and should be used for clinical decisions contributing to improve the diagnosis in this particular group in our country.
conferenceObject Evolution of milk-specific IgE antibody levels and its fractions during tolerance development in cow's milk allergic patients(2012) BECK, C.; CASTRO, A.; GUSHKEN, A.; WATANABE, L.; BRANDAO, A.; YONAMINE, G.; PASTORINO, A.; JACOB, C.Background: Food allergy affects about 6% of children and cow’s milk (CM) is the most important allergen. The majority of patients used to become tolerant during the first 3 years of life, but nowadays tolerance is being achieved later. Casein (C), alpha-lactalbumin (α) and beta-lactoglobulin (β) are considered as some of the major allergens. Until now, no study has evaluated the correlation among the whole cow’s milk (WCM) IgE antibody levels (IgE ab) and its fractions (C, α and β) during the tolerance development in CMA patients. Method: It was a retrospective study that included patients with previous diagnosis of CMA who developed tolerance during follow-up. It was included 31 IgE-mediated CMA patients (19 male: 12 female), median age of the first symptoms was 1 year. CMA was defined as a positive double blind placebo-controlled food challenge, open challenge or confirmed anaphylaxis plus cow’s milk-specific IgE positive (higher than 3.5 JU/l or positive skin prick test), and tolerance was defined as acceptance of cow milk without previous symptoms. Specific IgE analysis to WCM, α, β, and C were performed at three moments: initial (time 1), in the middle of the follow-up (time 2) and at the tolerance diagnosis (time 3). The chosen point during follow-up was that which corresponded to half of the period until tolerance was reached. The correlations among whole mil IgE ab and its fractions in those moments were evaluated with Spearman correlation test. Result: Ther values for whole cow’s milk IgE ab and each fraction according Spearman test are described in the following Table 1 Among all analysis, the correlation between whole cow’s milk and casein IgE ab and whole cow’s milk and alfalacto-albumin IgE ab showed adequater values at all moments of evaluations. Conclusion: These results can indicate that casein and alfalacto-albumin IgE ab showed similar behavior to WCM, and then the sequential evaluation through whole cow’s milk IgE ab levels may be enough for monitoring CMA patients until the tolerance development. Time Alpha-lactalbumin IgE ab Beta-lactoglobulin IgE ab Casein IgE ab 1 0.81 (0.63–0.90) 0.71 (0.46–0.85) 0.81 (0.64–0.91) 2 0.82 (0.65–0.91) 0.66 (0.39–0.82) 0.82 (0.65–0.91) 3 0.82 (0.64–0.91) 0.79 (0.60–0.90) 0.76 (0.54–0.90)- Common Variable Immunodeficiency Associated with Hepatosplenic T-Cell Lymphoma Mimicking Juvenile Systemic Lupus Erythematosus(2011) JESUS, A. A.; JACOB, C. M. A.; SILVA, C. A.; DORNA, M.; PASTORINO, A. C.; CARNEIRO-SAMPAIO, M.Common variable immunodeficiency (CVID) is a heterogeneous disorder with susceptibility to infections, autoimmune manifestations, and cancer. To our knowledge, CIVD with T-cell lymphoma mimicking juvenile systemic lupus erythematosus (JSLE) was not described in the literature, and one case was reported herein. An 8-year-old female was admitted in our Pediatric Immunology Unit with a clinical history of hypogammaglobulinemia, recurrent upper respiratory infections, and pneumonias. She had a marked decrease of three serum immunoglobulin isotypes, and the diagnosis of CVID was established. At the age of 17 years, she presented with oral ulceration, nonerosive arthritis, nephritis, serositis, cytopenia, positive antiphospholipid antibodies, and positive antinuclear antibody fulfilling the American College of Rheumatology (ACR) criteria for SLE. She was treated with intravenous methylprednisolone for three consecutive days, and intravenous immunoglobulin, and maintenance therapy of chloroquine, azathioprine and prednisone 40mg/day. Two months later, she died of septic shock secondary to acute pneumonia. The necropsy showed hepatosplenic T-cell lymphoma with diffuse involvement of bone marrow, spleen, liver, and lungs. The lymphoma cells were positive for CD3 immunostaining and negative for CD20 and lysozyme. In conclusion, the association of CVID and hepatosplenic T-cell lymphoma may simulate JSLE diagnosis.
- IPEX syndrome with Dent's disease manifestations - Case Report(2013) KOSTIC, Dusan; BRASIL, Saulo Couto; JACOB, Cristina Miuki Abe; SAMPAIO, Magda Carneiro; KOCH, Vera Hermina KalikaObjective: IPEX syndrome, a hereditary (X-linked) immune dysregulation with autoimmune polyendocrinopathy and enteropathy, as the basic manifestations, presents a rare and severe disease. The objective of this case report is to highlight the pleomorphism of the syndrome. Methods: The authors report the case of a male infant, with a family history of three male siblings affected by IPEX syndrome. The patients’ medical records were reviewed in order to describe the case of the youngest one. Results: During the follow-up of the youngest of three siblings, who presented eczema and intestinal manifestation, without compromised pancreatic and thyroid function, different from other two siblings, it was noticed the pattern of Dent’s disease. We registered hypophosphatemia, hypercalciuria, glycosuria, low molecular weight proteinuria and ultrasound revealed second stage bilateral nephrocalcinosis. In this child there was no apparent glomerular involvement, as it was seen in the eldest sibling. Conclusion: Dent’s disease is an X-linked renal proximal tubulopathy associated with mutations in the chloride channel gene CLCN5 (Xp11.22), which is next to FOXP3 gene on the X chromosome (Xp11.23-q13.3). It seems that in this sibling mutations occurred inexons of both of these genes. This case is to remind on pleomorphic potential of mutations that occur near the coding regions of the FOXP3 gene.
- Establishing a cut-off for the serum levels of specific IgE to milk and its components for cow's milk allergy: Results from a specific population(2015) CASTRO, A. P.; PASTORINO, A. C.; GUSHKEN, A. K. F.; KOKRON, C. M.; FILHO, U. D.; JACOB, C. M. A.Background: Cow's milk allergy diagnosis many times requires double-blind placebo-controlled food challenge (DBPCFC), which presents high accuracy but involves risks, specifically in infants and anaphylactic patients. The identification of the cut-off values for specific IgE to milk or its components would contribute to cow's milk allergy (CMA) diagnosis. The aim of this study was to compare discriminating concentration of a cow's milk specific IgE and its fractions (alpha-lactoalbumin, beta-lactoglobulin, casein) in children for the CMA diagnosis. Methods: this study included 123 patients (M:F= 1.3:1) median age at diagnosis = 1.91 years, (3.5 m to 13.21 y) with CMA diagnosis via DBPCFC (n = 26), proven anaphylaxis due to cow's milk (n = 46) or a suggestive clinical history associated with a positive skin prick test (n = 51) and open oral food challenge. The control group included 61 patients (1 male: 1.1 female) ages ranging from 0.66 to 16.7 years (median = 6.83 years). Receiver operator characteristics (ROC) curves were constructed to determine the best cut-offs that guarantees high specificity (>95%) for cow's milk and its components. Results: considering 98% specificity, cut-off points were: 3.06 kU/L for cow's milk, 2.06 kU/L for a-lactalbumin, 1.85 kU/L for beta-lactoglobulin and 1.47 kU/L for casein. The best ROC curve (area under the curve = 0.929) was obtained evaluating cow's milk. Conclusion: this study showed that the cut-off point detected for whole cow's milk revealed a better discriminatory capacity for CMA diagnosis without the necessity of the milk components testing.
- Baked milk tolerant patient: Is there any special feature?(2017) BARBOSA, C. P. G.; CASTRO, A. P. M.; YONAMINE, G. H.; GUSHKEN, A. K. F.; BECK, C. M. L.; MACEDO, P. R. C.; DORNA, M. B.; SANTOS, C. J. N.; PASTORINO, A. C.; JACOB, C. M. A.Background: Determining whether patients with cow's milk allergy (CMA) can tolerate foods produced with baked milk could provide a better quality of life, a better prognosis, and an option for desensitization. Objectives: The aim of this study was to identify which patients over four years of age with persistent CMA could tolerate baked milk, to compare the clinical and laboratory characteristics of reactive and non-reactive groups and to describe their clinical evolution. Materials and methods: A cross-sectional study was conducted (January/13 to November/14) that included all the patients followed at a food allergy center who met the inclusion criteria. The patients underwent an oral food challenge (OFC) with a muffin (2.8 g of cow's milk protein). To exclude cow's milk (CM) tolerance, the patients were subsequently challenged with unheated CM. Results: Thirty patients met all the inclusion criteria. Fourteen patients (46.7%) were considered non-reactive to baked milk and reactive to unheated CM. When the groups that were reactive and non-reactive to baked milk were compared, no statistically significant differences in clinical features were found. The prick test for alpha-lactalbumin (p = 0.01) and casein (p = 0.004) and the serum specific IgE for casein (p = 0.05) presented statistical differences. After one year, none of the patients who were reactive to baked milk were ingesting CM, while 28% of the tolerant patients were consuming fresh CM (p= 0.037). Conclusions: Baked milk can be tolerated by patients with CMA, especially those with lower levels of casein and a-lactalbumin. This option can improve quality of life and accelerate tolerance.
- The Extended Clinical Phenotype of 26 Patients with Chronic Mucocutaneous Candidiasis due to Gain-of-Function Mutations in STAT1(2016) DEPNER, Mark; FUCHS, Sebastian; RAABE, Jan; FREDE, Natalie; GLOCKER, Cristina; DOFFINGER, Rainer; GKRANIA-KLOTSAS, Effrossyni; KUMARARATNE, Dinakantha; ATKINSON, T. Prescott; SCHROEDER JR., Harry W.; NIEHUES, Tim; DUECKERS, Gregor; STRAY-PEDERSEN, Asbjorg; BAUMANN, Ulrich; SCHMIDT, Reinhold; FRANCO, Jose L.; ORREGO, Julio; BEN-SHOSHAN, Moshe; MCCUSKER, Christine; JACOB, Cristina Miuki Abe; CARNEIRO-SAMPAIO, Magda; DEVLIN, Lisa A.; EDGAR, J. David M.; HENDERSON, Paul; RUSSELL, Richard K.; SKYTTE, Anne-Bine; SENEVIRATNE, Suranjith L.; WANDERS, Jennifer; STAUSS, Hans; MEYTS, Isabelle; MOENS, Leen; JESENAK, Milos; KOBBE, Robin; BORTE, Stephan; BORTE, Michael; WRIGHT, Dowain A.; HAGIN, David; TORGERSON, Troy R.; GRIMBACHER, BodoPurpose Gain-of-function (GOF) mutations in the signal transducer and activator of transcription 1 (STAT1) result in unbalanced STAT signaling and cause immune dysregulation and immunodeficiency. The latter is often characterized by the susceptibility to recurrent Candida infections, resulting in the clinical picture of chronic mucocutaneous candidiasis (CMC). This study aims to assess the frequency of GOF STAT1 mutations in a large international cohort of CMC patients. Methods STAT1 was sequenced in genomic DNA from 57 CMC patients and 35 healthy family members. The functional relevance of nine different STAT1 variants was shown by flow cytometric analysis of STAT1 phosphorylation in patients' peripheral blood cells (PBMC) after stimulation with interferon (IFN)-alpha, IFN-gamma or interleukin-27 respectively. Extended clinical data sets were collected and summarized for 26 patients. Results Heterozygous mutations within STAT1 were identified in 35 of 57 CMC patients (61 %). Out of 39 familial cases from 11 families, 26 patients (67 %) from 9 families and out of 18 sporadic cases, 9 patients (50 %) were shown to have heterozygous mutations within STAT1. Thirteen distinct STAT1 mutations are reported in this paper. Eight of these mutations are known to cause CMC (p.M202V, p.A267V, p.R274W, p.R274Q, p.T385M, p.K388E, p.N397D, and p.F404Y). However, five STAT1 variants (p.F172L, p.Y287D, p.P293S, p.T385K and p.S466R) have not been reported before in CMC patients. Conclusion STAT1 mutations are frequently observed in patients suffering from CMC. Thus, sequence analysis of STAT1 in CMC patients is advised. Measurement of IFN- or IL-induced STAT1 phosphorylation in PBMC provides a fast and reliable diagnostic tool and should be carried out in addition to genetic testing.