CRISTINA MIUKI ABE JACOB
Projetos de Pesquisa
Unidades Organizacionais
LIM/36 - Laboratório de Pediatria Clínica, Hospital das Clínicas, Faculdade de Medicina - Líder
11 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.- 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.
- 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.
- 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.
conferenceObject T-CELL- AND ANTIBODY-MEDIATED AUTOIMMUNE MANIFESTATIONS IN SCID DUE TO IL7RA MUTATIONS(2012) ZAGO, C. A.; JACOB, C. M. A.; DINIZ, E. M. D. A.; ZERBINI, C.; DORNA, M.; FERNANDES, J.; ROCHA, V.; OLIVEIRA, J. B.; CARNEIRO-SAMPAIO, M.Introduction: B+ SCID due to IL7Ra deficiency represents around 10% of SCID cases, and has seldom been described among Brazilian patients. Objective: We present two unrelated SCID female infants with IL7RA mutations and distinct autoimmune manifestations. Case 1: This infant was born to non-consanguineous parents at 28 weeks of gestational age presenting characteristic clinical as pects of Omenn syndrome (OS). She died after 2 days due to meconium-aspiration pneumonitis and pancarditis (with eosinophil and histiocyte infiltration). She presented leukocytosis (19,500/mm3), eosinophilia (4,860cells/mm3), lymphocytes=2,925cells/mm3 (CD3+=684cells/mm3, CD4+=345cells/mm3, CD8+=6cells/mm3, without naive T-cells, CD25+Foxp3+=2.3%, CD19+=641cells/mm 3, CD3-CD16+CD56+=280cells/mm3), thrombocytopenia=49,000/mm3, IgG=468mg/dL, IgM=45mg/dL, IgA<22mg/dL, IgE=3,310UI/ml. She harbored a homozygous p.C118Y IL7RA mutation. She is the second IL7Ra deficient OS in literature; the first described case presented the same mutation and was also Brazilian. Case 2: An 8-month-old girl presented since 4 months-old with severe thrombocytopenic purpura, treated with high IVIg doses and corticosteroids. She presented lymphocytopenia=1,287cells/mm3 (CD3=147cells/mm3, CD4=36cells/mm3, CD8=72cells/mm3), normal B (184cells/mm3, 80% withs IgM+IgD+) and NK numbers (259cells/mm3), very low TRECs, IgM=235mg/dL, IgA=51mg/dL, IgE=5UI/ml, and positive anti-nuclear antibodies (1/320). A sister with an equivalent clinical picture died at 15 months of age. She had compound heterozygous p.C118Y and p.I121NfsX8 IL7RA mutations. She did not present serious infections, and was successfully transplanted with cord blood cells at 13-months-old. Conclusions: Autoimmune diseases associated to “leaky” SCIDs due to IL7RA mutations may be mediated by both autoreactive T lymphocytes (probably in case1, an intrauterine OS) and autoantibodies (probably the predominant pathogenic mechanism in case2).- Fluticasone/formoterol dry powder versus budesonide/formoterol in adults and adolescents with uncontrolled or partly controlled asthma(2013) CUKIER, A.; JACOB, C. M. A.; ROSARIO FILHO, N. A.; FITERMAN, J.; VIANNA, E. O.; HETZEL, J. L.; NEIS, M. A.; FISS, E.; CASTRO, F. F. M.; FERNANDES, A. L. G.; STIRBULOV, R.; PIZZICHINI, E.This 12-week study compared the efficacy and safety of a fixed combination of fluticasone propionate plus formoterol (FL/F) 250/12 mu g b.i.d. administered via a dry powder inhaler (DPI) (Libbs Farmaceutica, Brazil) to a combination of budesonide plus formoterol (BD/F) 400/12 mu g b.i.d. After a 2-week run-in period (in which all patients were treated exclusively with budesonide plus formoterol), patients aged 12-65 years of age (N = 196) with uncontrolled asthma were randomized into an actively-controlled, open-labeled, parallel-group, multicentre, phase III study. The primary objective was to demonstrate non-inferiority, measured by morning peak expiratory flow (mPEF). The non-inferiority was demonstrated. A statistically significant improvement from baseline was observed in both groups in terms of lung function, asthma control, and the use of rescue medication. FL/F demonstrated a statistical superiority to BD/F in terms of lung function (FEV1) (p = 0.01) and for asthma control (p = 0.02). Non-significant between-group differences were observed with regards to exacerbation rates and adverse events. In uncontrolled or partly controlled asthma patients, the use of a combination of fluticasone propionate plus formoterol via DPI for 12-weeks was non-inferior and showed improvements in FEV1 and asthma control when compared to a combination of budesonide plus formoterol. (Clinical Trial number: ISRCTN60408425).
conferenceObject RESTRICTED AND SKEWED TCR VB REPERTOIRE IN CHROMOSOME 22Q11.2 DELETION(2012) ARANTES, J. M.; GRASSI, M. S.; SANTOS, N. M.; GUILHERME, L.; KULIKOWSKI, L. D.; DUTRA, R. L.; WATANABE, L. A.; JACOB, C. M. A.; ZAGO, C. A.; CARNEIRO-SAMPAIO, M.Introduction: Chromosome 22q11 deletion is the most common human deletion and is found in the majority of patients with DiGeorge and velo-cardio-facial syndromes. Many patients have a mild to moderate immunodeficiency, and most have cardiac anomaly. Objective: To evaluate TCR repertoire diversity in infants with 22q11.2 deletion identified at FMUSP ward for congenital heart diseases. Methods: TCR Vβ variable chain repertoire was analyzed by the TCRBV CDR3 lenght spectratyping technique, and repertoire diversity was quantified utilizing the complexity score (CS), that represents the sum of the number of peaks for each one of the 24 BV families. 22q11.2 deletion was detected utilizing multiplex ligation-dependent probe amplification. First case report: A 9-month-old boy was identified in a survey among infants with complex congenital heart anomalies. He was born from non-consanguineous parents, weighing 2845g and presenting microcephaly, micrognathia, ocular hypertelorism and low set left ear, renal involvement, left atrial isomerism and pulmonary atresia. He also had hypocalcemia and hypoplasticthymus. He has lymphopenia=3,800 cells/mm3 (CD3=1,454 cells/mm3, CD4=888cells/mm3, CD8=537cells/mm3), thrombocytopenia=55,000, IgG+=1,285mg/dL, IgM=123mg/dL, IgA=132mg/dL. Results: The patient presented CS=49, in contrast with 2 healthy age-matched male infants with 127 and 135. Four young healthy adults presented CS between 165 and 178. The patient presented mostly olygoclonal distribution and even absence of TCRBV families, while healthy donors exhibited mainly polyclonal non-Gaussian distributions. Conclusions: The evaluation of new cases as well as the follow-up the patients will demonstrate if the repertoire diversity correlates with clinical severity.conferenceObject MUTATION SCREENING IN STAT1, CARD9 AND PKC-DELTA IN PATIENTS WITH CHRONIC MUCOCUTANEOUS CANDIDIASIS(2012) DEPNER, M.; VEERDONK, F. van de; WANDERS, J.; STAUSS, H.; RAABE, J.; ATKINSON, T. P.; SCHROEDER JR., H. W.; NIEHUES, T.; DUECKERS, G.; PUCK, J.; STRAY-PEDERSEN, A.; BAUMANN, U.; SCHMIDT, R.; FRANCO, J. L.; ORREGO, J.; BEN-SHOSHAN, M.; MCCUSKER, C.; JACOB, C. M. A.; CARNEIRO-SAMPAIO, M.; DEVLIN, L. A.; EDGAR, J. D.; GKRANIA-KLOTSAS, E.; KUMARARATNE, D.; DOFFINGER, R.; HENDERSON, P.; RUSSELL, R. K.; DYRSO, T.; SENEVIRATNE, S. L.; MATTHIJS, G.; ABINUN, M.; GENNERY, A.; JOHNSON, M.; MEER, J. W. M. van der; NETEA, M. G.; LILIC, D.; GRIMBACHER, B.- Prediction of tolerance in children with IgE mediated cow's milk allergy by microarray profiling and chemometric approach(2012) WULFERT, F.; SANYASI, G.; TONGEN, L.; WATANABE, L. A.; WANG, X.; RENAULT, N. K.; FALCONE, F. H.; JACOB, C. M. A.; ALCOCER, M. J. C.The sera of a retrospective cohort (n = 41) composed of children with well characterized cow's milk allergy collected from multiple visits were analyzed using a protein microarray system measuring four classes of immunoglobulins. The frequency of the visits, age and gender distribution reflected real situation faced by the clinicians at a pediatric reference center for food allergy in 530 Paulo, Brazil. The profiling array results have shown that total IgG and IgA share similar specificity whilst IgM and in particular IgE are distantly related. The correlation of specificity of IgE and IgA is variable amongst the patients and this relationship cannot be used to predict atopy or the onset of tolerance to milk. The array profiling technique has corroborated the clinical selection criteria for this cohort albeit it clearly suggested that 4 out of the 41 patients might have allergies other than milk origin. There was also a good correlation between the array data and ImmunoCAP results, casein in particular. By using qualitative and quantitative multivariate analysis routines it was possible to produce validated statistical models to predict with reasonable accuracy the onset of tolerance to milk proteins. If expanded to larger study groups, the array profiling in combination with the multivariate techniques show potential to improve the prognostic of milk allergic patients.