CRISTINA MIUKI ABE JACOB
Projetos de Pesquisa
Unidades Organizacionais
LIM/36 - Laboratório de Pediatria Clínica, Hospital das Clínicas, Faculdade de Medicina - Líder
13 resultados
Resultados de Busca
Agora exibindo 1 - 10 de 13
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)conferenceObject Profiling using protein x basophil array: current progress(2012) WANG, X.; WAN, D.; JACOB, C.; FALCONE, F.; ALCOCER, M.Background: Correlation between observed allergic clinical symptoms and specific IgE levels is poor in some cases. Current developments on basophil activation tests (BAT) are showing improved clinic relevance (compared to DBPCFC) than specific IgE alone. We are developing a two stages diagnostic device which combines the advantages of BAT with the numerical power of protein microarrays. Previously we have shown that a four immunoglobulin platform for simultaneous detection of IgM, A, G and E was feasible. We then demonstrated as proof-of-principle that human peripheral blood basophils and humanised basophil cell lines can bind to a protein array and that activation can be detected. Here we show an application of the basic platform (protein array) and discuss current stages of development of the basophil array system. Method: Microarrays containing proteins and extracts of food products, enterobacteria and inhaled allergens have been hybridised with sera from a retrospective longitudinal trial of children with clinically well-characterized cow’s milk allergy (n= 41) and control sera (n= 20) as previously described. The IgM, A, G and E levels have been determined and were analysed using chemometric multivariate routines. For the second stage (basophil cells), binding and incubation parameters to the array were experimentally optimised for three independent cell lines. Basophil cell activation markers involving Annexin V binding, Calcium influx and fluorescent inducible reporter systems have been compared to enzymatic degranulation tests. Result: The basic platform (protein array only) has shown that total IgG and IgA share similar specificity whilst IgM and IgE in particular are distantly related. The array has shown that four out of the 41 patients might have allergies other than milk origin. A good correlation (r2> 0.7) between dairy IgE and ImunoCAP, casein in particular, was observed. In the basophil system (2nd stage platform), measurement of Annexin V and calcium influx produced expected degranulation endpoints however, fluorescent reporter genes have shown higher sensitivity. The lack of stability of cells after successive passages is still a major issue. Conclusion: The basic platform (protein array) for the comprehensive profiling tools has produced qualitatively and quantitative reproducible results. The optimisation of the second component (basophil cells) of the profiling platform that is, reporter genes for key steps.conferenceObject Sensitisation to foods and dust mite in Brazilian pediatric patients with atopic dermatitis(2012) SWENSSON, A.; CASTRO, A.; CASAGRANDE, R.; BITTENCOURT, T.; YONAMINE, G.; PASTORINO, A.; JACOB, C.Background: Atopic dermatitis (AD) is a complex disease that can be or not related to atopy. The IgE levels and the presence of sensitisation has been associated to AD severity. The aim of this study is to evaluate the allergen sensitisation profile in patients with moderate or severe atopic dermatitis in Brazilian patients from an allergy reference center. Methods: About 66 patients with diagnosis of atopic dermatitis according Hanifin e Rajka criteria (mean age 10 years) followed at a reference center for allergic disease in pediatric patients were included. The severity was evaluated according SCORAD (SCORing Atopic Dermatitis) criteria. Specific IgE was measured to the following allergens: Blomia tropicalis, D peteronyssinus, egg white, cow’s milk and its fractions. Sensitisation was considered positive when the ImmunoCAP values were ¡Y 0.35 kU/l and multi sensitisation was considered when patients presented positive specific IgE for all allergens tested. Table 1 Hapten Total, positive (n,%) Total, clinically relevant (n,%) Children, positive (n,%) Children, clinically relevant (n,%) Adolescents, positive (n,%) Adolescents, clinically relevant (n,%) Nickel sulphate 5% pet. 44 (34.6) 36 (28.3) 19 (29.7) 14 (21.9) 25 (39.7) 22 (34.9) Cobalt chloride 1% pet. 28 (22.0) 15 (11.8) 16 (25.0) 9 (14.1) 12 (19.0) 6 (9.5) Potassium dichromate 0.5% pet. 26 (20.5) 15 (11.8) 19 (29.7) 10 (15.6) 7 (11.1) 5 (7.9) Paraphenylenediamine 1% pet. 12 (9.4) 6 (4.7) 8 (12.5) 5 (7.8) 4 (6.3) 1 (1.6) Propolis 10% pet. 12 (9.4) 5 (3.9) 11 (17.2) 5 (7.8) 1 (1.6) 0 (0.0) Palladium chloride 2% pet. 12 (9.4) 4 (3.1) 6 (9.4) 2 (3.1) 6 (9.5) 2 (3.2) Fragrance Mix I 18% pet. 10 (7.9) 4 (3.1) 4 (6.3) 2 (3.1) 6 (9.5) 2 (3.2) Neomycin sulphate 20% pet. 6 (4.7) 2 (1.6) 4 (6.3) 2 (3.1) 2 (3.2) 0 (0.0) Balsam of Peru (Myroxylon pereirae ) 25% pet. 6 (4.7) 1 (0.8) 4 (6.3) 1 (1.6) 2 (3.2) 0 (0.0) Colophonium 20% pet. 5 (3.9) 4 (3.1) 2 (3.1) 2 (3.1) 3 (4.8) 2 (3.2) Wool alcohols (lanolin) 30% pet. 5 (3.9) 3 (2.4) 3 (4.7) 3 (4.7) 2 (3.2) 0 (0.0) Paraben Mix 16% pet. 4 (3.1) 4 (3.1) 3 (4.7) 3 (4.7) 1 (1.6) 1 (1.6) Kathon CG (MI/MCI) 0.01% aqua 4 (3.1) 2 (1.6) 3 (4.7) 2 (3.1) 1 (1.6) 0 (0.0) Results: Among 66 patients included, 12 presented severe AD and 54 moderated. Sixty two of the 66 (93%) patients studied showed positive sensitization to any of the allergens, being aeroallergens the most prevalent (53/56), followed by egg white (29/53) and milk (31/66). Serum levels of specific IgE to aerollergens were significantly higher than for food allergens (P< 0.001). Specific IgE levels did not differ according severity (P> 0.05 for all allergens evaluated About 23 patients presented multi sensitization (17 moderate and six severe) without significant difference between both groups. Conclusion: There was an elevate rate of sensitisation in this group of patients being aeroallergens the most frequent and with higher specific IgE levels. AD severity did not contribute to increase sensitisation. More studies should be performed in order to evaluate if these findings can lead to specific therapeutic strategies as specific immunotherapy or food avoidance.conferenceObject Pulmonary Morphologic and Functional Abnormalities in Patients with Primary Hypogammaglobulinemia(2012) DORNA, Mayra de Barros; CASTRO, Ana Paula B. Moschione; PASTORINO, Antonio Carlos; CARNEIRO-SAMPAIO, Magda M. Sales; JACOB, Cristina Miuki AbeRetrospective evaluation of 30 patients (21 M) aged 4.6–23.4 y (median 16.7 y) with predominantly humoral PID(9IDCV;14XLA;7HIGM).Mediantimeof follow-up9.2y(1.8–17.5). Median age of symptoms’ onset8mo(1–96 mo), age at diagnosis 5.8 y (7–175 mo) and diagnostic delay 4.7 y (0.2–13 y). Pneumonia was the main manifestation before diagnosis (24/30 patients) with frequency of 0.6/patient/year. After beginning IVIG, frequency of pneumonias decreased to 0.1 (p<0.001) and the frequency of sinusitis increased from0to0.55(p<0.001). Higher age at diagnosis and longer diagnostic delay were associated to bronchiectasis at diagnosis (p=0.016 and p<0.001). Seven patients developed bronchiectasis during follow-up. Spirometry (23/30 patients), 1–15 y after IVIG was abnormal in 13 (9 obstructive; 4 restrictive). Humoral PID often affects respiratory tract and IVIG reduces complications but pulmonary monitoring is essential to guarantee adequate therapeutic interventions.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).conferenceObject SERIOUS OPHTHALMOLOGIC COMPLICATIONS OF PRIMARY IMMUNODEFICIENCY PATIENTS(2012) ALVAREZ, H. T.; SUZUKI, A. C. F.; TAKIUTI, J. H.; FERRIANI, M. P.; DORNA, M.; SANTOS, C.; PASTORINO, A. C.; CASTRO, A. P. B.; CARNEIRO-SAMPAIO, M.; JACOB, C. M.Introduction: Primary immunodeficiencies (PID) are genetic diseases characterized by high susceptibility to infections. Although the manifestations affect all organs, there are few reports about ocular complications. Objective: To describe four patients with serious ophthalmologic complications in Brazilian patients followed at a reference center for PID. Methods: It was a retrospective study including patients with ocular serious complains. Medical records of 4 PID patients were evaluated for clinical data and the PID diagnosis was based on the PAGID/ ESID criteria. These patients underwent to ophthalmologic evaluation, including visual acuity, biomicroscopy and fundus examination. Ophthalmologic evaluation was done routinely only for AT and CHS diagnosis. Results: The PIDs patients included were: HLH, GCD, CMC and A-T. The HLH patient had a heterozygous mutation at the perforin gene (FHL type 2), CMC patient had a heterozygous mutation at STAT1. Ocular complains were: ocular pain, hyperemia, eyelids edema and strabismus and the characteristics of each patient were: - Female, 13y, CMC- conjunctivitis and eyelids edema with infraorbital infected papules. - Female, 6 mo, HLH- acute strabismus in consequence of neurological involvement by HLH. - Male, 15y, AT- herpes conjunctivitis and loss of vision in left eye. - Male, 9y CGD - Conjunctivitis in the left eye, progressing to edema and proptosis. The diagnosis was endophthalmitis granulomatous with loss of vision in left eye. Conclusion: Although not common in PID patients, the ocular complications may lead to loss of vision. The ophthalmologic evaluation would be routinely recommended for all PID patients to avoid important sequels.conferenceObject Familial Hemophagocytic Lymphohistiocytosis Caused by Perforin Deficiency in Brazilian Twins(2012) JACOB, Cristina Miuki Abe; SANTOS, Cristiane de Jesus Nunes dos; SAINT-BASILE, Genevieve de; CASTRO, Ana Paula B. Moschione; PASTORINO, Antonio Carlos; FERNANDES, Juliana Folloni; ROCHA, Vanderson; CARNEIRO-SAMPAIO, Magda M. SalesTwo female monozygotic twins presented: Case1-at2mo presented fever and vomiting after vaccination with DTP, Haemophilus, Salk, Rotavirus. The initial evaluation showed: anemia, hepatosplenomegaly, pancytopenia, LDH=0760 U/L, ferritin=0622 ng/mL and triglycerides=0362 mg/dL. Hemophagocytosis was found in bone marrow. Case2: clinically asymptomatic, being detected anemia, LDH=0726 U/L, ferritin=0436 ng/mL, triglycerides=0166 mg/dL, without hemophagocytosis. Infections were excluded in both. Molecular testing identified two heterozygous mutations in the perforin gene, C46T leading to P16S and 50delT leading to L17 stop, making the diagnosis of FHL type 2. Both twins underwent to therapy based on HLH-2004 protocol followed by cord blood transplantation and after CMV infection with a good response to treatment. FHL should be suspected in all children with fever, visceromegaly and cytopenias for early treatment, including hematopoietic stem cell transplantation.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.bookPart Manejo da alergia ao leite de vaca(2012) JACOB, Cristina Miuki Abe; PASTORINO, Antonio CarlosconferenceObject Ataxia-Telangiectasia and CD8+T Cells Acute Lymphoid Leukemia in a Brazilian Patient: A Case Report(2012) FERREIRA, Leticia Bellinaso; DIAS, Diana Kimie; CASTRO, Ana Paula B. Moschione; PASTORINO, Antonio Carlos; DORNA, Mayra de Barros; ZAMPERLINI, Gustavo; CARNEIRO-SAMPAIO, Magda M. Sales; JACOB, Cristina Miuki AbeA Brazilian boy with Ataxia-Telangiectasia (AT) diagnosed at 7 years of age, looked for the hospital at the age of 9 complaining of vomiting and disseminated hematomas for 10 days. The initial evaluation revealed only anemia (Hb=8,3 g/dL) and thrombocytopenia (19000 platelets/mm3). The bone marrow aspirate showed 90% of lymphoid blasts, being diagnosed CD8+ T cells acute leukemia and the patient was submitted to chemotherapy. During the treatment, he developed pneumonia, hepatomegaly and acute tumor lysis syndrome, followed by septic shock and acute renal failure. Despite intensive care efforts, he died a month after cancer diagnosis. AT is a neurodegenerative disease, associated to immunodeficiency, high sensitivity to ionizing radiation and predisposition to cancer. This case revealed how aggressive could be a neoplasia in AT patients, in which a careful cancer surveillance is mandatory, with clinical and laboratorial control, avoiding unnecessary radiation exposure.