Neonatal screening for severe combined immunodeficiency in Brazil

Kanegae, Marilia Pyles Patto; Barreiros, Lucila Akune; Mazzucchelli, Juliana Themudo Lessa; Hadachi, Sônia Marchezi; Guilhoto, Laura Maria de Figueiredo Ferreira; Acquesta, Ana Lúcia; I, Genov; Holanda, Silvia Maia; Gesu, Regina Sumiko Watanabe Di; Goulart, Ana Lúcia; Santos, Amélia Miyashiro Nunes dos; Bellesi, Newton; Costa‐Carvalho, Beatriz Tavares; Condino‐Neto, Antônio

doi:10.1016/j.jped.2015.10.006

Cited by 22 publications

(13 citation statements)

References 19 publications

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“…Thus, after quantification of almost 7,000 samples, receiver operating characteristic curve was analyzed, and cutoff values of 15 TRECs/µL and 14 KRECs/µL, with 100% sensitivity for detection of SCID and agammaglobulinemia, respectively, were found. These values are very close to those reported by Borte et al 8 (15 TRECs/uL and 10 KRECs/uL) and resulted in a repetition rate of 0.49% (34 samples), which was very close to the value found in our previous work 9 . After the reanalysis of these 34 samples that were below the new cutoff values, only two samples (0.03%) remained altered.…”

Section: Discussionsupporting

confidence: 90%

“…For the first 1,000 samples analyzed, cutoff values of 25 TRECs/µL and 25 KRECs/µL were initially applied, which resulted in a high repetition rate - 2.5% of the samples had concentrations below the cutoff values in a first analysis - compared to a previous work of our group, 9 but still within the range reported by other authors (0.20-3.26%) 4 . One possibility for this high repetition rate was the use of a plasmid which was different from the previously employed - only contained the sequence of TRECs.…”

Section: Discussionmentioning

confidence: 99%

“…A previous work carried out by our group, which was pioneer in the country, has validated the TRECs quantification methodology for neonatal screening for SCID 9 . This study aimed at validating the quantification of TRECs and KRECs in the same reaction by quantitative real-time PCR (qRT-PCR) for neonatal screening of primary immunodeficiencies which occur with defects in T and/or B cells.…”

Section: Introductionmentioning

confidence: 99%

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Triagem Neonatal De Imunodeficiências Graves Combinadas Por Meio De Trecs E Krecs: Segundo Estudo Piloto No Brasil

Kanegae

Barreiros

Sousa

et al. 2017

Rev. paul. pediatr.

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Objective: To validate the quantification of T-cell receptor excision circles (TRECs) and kappa-deleting recombination excision circles (KRECs) by real-time polymerase chain reaction (qRT-PCR) for newborn screening of primary immunodeficiencies with defects in T and/or B cells in Brazil.Methods: Blood samples from newborns and controls were collected on filter paper. DNA was extracted and TRECs, and KRECs were quantified by a duplex real-time PCR. The cutoff values were determined by receiver operating characteristic curve analysis using SPSS software (IBM®, Armonk, NY, USA).Results: Around 6,881 samples from newborns were collected and TRECs and KRECs were quantified. The TRECs values ranged between 1 and 1,006 TRECs/µL, with mean and median of 160 and 139 TRECs/µL, respectively. Three samples from patients with severe combined immunodeficiency (SCID) showed TRECs below 4/µL and a patient with DiGeorge syndrome showed undetectable TRECs. KRECs values ranged from 10 to 1,097 KRECs/µL, with mean and median of 130 and 108 KRECs/µL. Four patients with agammaglobulinemia had results below 4 KRECs/µL. The cutoff values were 15 TRECs/µL and 14 KRECs/µL and were established according to the receiver operating characteristic curve analysis, with 100% sensitivity for SCID and agammaglobulinemia detection, respectively.Conclusions: Quantification of TRECs and KRECs was able to diagnose children with T- and/or B-cell lymphopenia in our study, which validated the technique in Brazil and enabled us to implement the newborn screening program for SCID and agammaglobulinemia.

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Section: Discussionsupporting

confidence: 90%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Triagem Neonatal De Imunodeficiências Graves Combinadas Por Meio De Trecs E Krecs: Segundo Estudo Piloto No Brasil

Kanegae

Barreiros

Sousa

et al. 2017

Rev. paul. pediatr.

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“…Moreover, delaying BCG vaccination would also benefit the clinical impact of neonatal SCID screening, preventing application of an absolutely contraindicated vaccine prior to establishing the diagnosis of SCID. This issue will become increasingly relevant as countries still encouraging early BCG vaccination start implementing neonatal SCID screening 19 20 . However, two major drawbacks could be foreseen in delaying BCG vaccination: the “missed opportunity” of vaccinating patients after birth based on the concept that there will be an associated decline in coverage, and the very low potential increased risk of BCG-preventable diseases during the “unprotected” intervals.…”

Section: Discussionmentioning

confidence: 99%

BCG vaccination in patients with severe combined immunodeficiency: Complications, risks, and vaccination policies

Marciano

Huang

Joshi

et al. 2014

Journal of Allergy and Clinical Immunology

203

195

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Background SCID is a syndrome characterized by profound T cell deficiency. BCG vaccine is contraindicated in SCID patients. Because most countries encourage BCG vaccination at birth, a high percent of SCID patients are vaccinated before their immune defect is detected. Objectives To describe the complications and risks associated with BCG vaccination in SCID patients. Methods An extensive standardized questionnaire evaluating complications, therapeutics, and outcome regarding BCG in patients diagnosed with SCID was widely distributed. Summary statistics and association analysis was performed. Results Data on 349 BCG vaccinated SCID patients from 28 centers in 17 countries was analyzed. Fifty-one percent of the patients developed BCG complications, 34% disseminated and 17% localized (a 33,000 and 400 fold increase, respectively, over the general population). Patients receiving early vaccination (≤ 1 month) showed an increased prevalence of complications (p=0.006) and death due to BCG complications (p<0.0001). The odds of experiencing complications among patients with T cells ≤ 250/uL at diagnosis was 2.1 times higher (95% CI, 1.4-3.4; p = 0.001) than among those with T cells > 250/uL. BCG complications were reported in 2/78 patients who received anti-mycobacterial therapy while asymptomatic and no deaths due to BCG complications occurred in this group. In contrast 46 BCG-associated deaths were reported among 160 patients treated with anti-mycobacterial therapy for a symptomatic BCG infection (p<0.0001). Conclusions BCG vaccine has a very high rate of complications in SCID patients, which increase morbidity and mortality rates. Until safer and more efficient anti-tuberculosis vaccines become available, delay in BCG vaccination should be considered to protect highly vulnerable populations from preventable complications.

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“…As complicações infecciosas levam grande parte dos pacientes SCID à óbito antes do diagnóstico, durante a espera ou logo após o transplante. Por causa disso é imprescindível que os pacientes sejam identificados precocemente, passem por investigação de patógenos minuciosa e caso haja uma infecção, ela deve ser tratada rápida e agressivamente (Gaspar, 2013 (Audrain et al, 2014), Espanha (Olbrich et al, 2014), Irã (Fazlollahi et al, 2017) e Brasil (Kanegae et al, 2016;Kanegae et al, 2017). Todas essas iniciativas concluíram que esse teste se mostrou sensível para a detecção de recém-nascidos portadores de SCID (Buelow, Verbsky, Routes, 2016), e de vantagem econômica ao se comparar os gastos para o manejo de um paciente SCID antes e após o aparecimento de infecções (Chan, Davis, Pai, 2011;Kubiak et al, 2014;Modell, Knaus, Modell, 2014;Gardulf, 2016).…”

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Investigação genético-molecular de pacientes com imunodeficiência combinada grave

Barreiros¹,

Neto²

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AGRADECIMENTOSAgradeço a todos que contribuíram com este trabalho, na forma de apoio científico, financeiro, acadêmico e emocional.Ao Instituto de Ciências Biomédicas e ao Departamento de Imunologia pelos recursos investidos. A todos os professores e professoras que despertaram cada vez mais meu interesse pela imunologia e a ciência de maneira geral. À Fundação Jeffrey Modell, que financiou parte deste estudo e minha estadia no Seattle Children's Research Institute, na Universidade de Washington. Agradeço à toda a equipe do Dr. Hans D. Ochs pela ajuda, acolhimento e carinho em Seattle. Ao meu orientador, Antonio Condino Neto, por ter me aceitado no Laboratório de Imunologia Humana (LIH) e me proporcionado experiências acadêmicas e científicas únicas. À toda equipe do LIH, por todo apoio não só intelectual, mas emocional. Os cafés, almoços, lanchinhos e congressos com meus pares são grande parte dos responsáveis pelo meu crescimento científico e pessoal. Agradeço especialmente Jusley e Edson, por todos os dias em que dividiram as tarefas comigo, permitindo que eu pudesse me dedicar à dissertação. E Christina e Silvana, sem as quais a vida no laboratório seria impraticável. À Marília Kanegae por ter aberto minha linha de pesquisa, ter sido a minha mentora e me ensinado (quase) tudo o que precisei para desenvolver não só o estudo, mas minha vida profissional como um todo. Aos meus amigos, meus biólogos, pelo apoio e as risadas constantes por 10 anos. O caminho até aqui seria cinza sem vocês. Ao Luiz, por todo o amor, carinho, paciência, paciência e paciência. À minha família, em especial aos meus pais, por me proporcionarem diariamente os exemplos compromisso e persistência, e por terem me dado total liberdade e apoio para fazer da minha vida profissional e pessoal absolutamente o que eu quisesse. Esse trabalho é dedicado a todos vocês. EPÍGRAFE (Fernando Gonsales [data desconhecida]) RESUMO Barreiros, LA. Investigação genético-molecular de pacientes com Imunodeficiência Combinada Grave.A imunodeficiência combinada grave (SCID) é uma doença caracterizada por profunda deficiência de células T, que afeta as imunidades celular e humoral e gera anormalidades graves no desenvolvimento e funções do sistema imune. Recém-nascidos com SCID apresentam a doença nos primeiros meses de vida e tem grande susceptibilidade a infecções. Sem tratamento, essas condições são invariavelmente fatais, porém se reconhecidas precocemente, há a possibilidade da realização do transplante de células-tronco hematopoiéticas, o tratamento curativo, o que torna a SCID uma emergência pediátrica. A investigação do defeito genético é uma prerrogativa para o condicionamento adequado do transplante, a terapia gênica, o aconselhamento genético e o diagnóstico pré-natal. No Brasil, o conhecimento sobre SCID é incipiente e não existem dados moleculares sobre pacientes com a doença. Sendo assim, este estudo teve por objetivo investigar defeitos genético-moleculares de pacientes brasileiros com SCID. Foram incluídos 13 pacientes, todos com início precoce do...

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Neonatal screening for severe combined immunodeficiency in Brazil

Abstract: The technique is reliable and can be applied on a large scale after the training of technical teams throughout Brazil.

Cited by 22 publications

References 19 publications

Triagem Neonatal De Imunodeficiências Graves Combinadas Por Meio De Trecs E Krecs: Segundo Estudo Piloto No Brasil

Triagem Neonatal De Imunodeficiências Graves Combinadas Por Meio De Trecs E Krecs: Segundo Estudo Piloto No Brasil

BCG vaccination in patients with severe combined immunodeficiency: Complications, risks, and vaccination policies

Investigação genético-molecular de pacientes com imunodeficiência combinada grave

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