Hematopoietic Cell Transplantation in Patients With Primary Immune Regulatory Disorders (PIRD): A Primary Immune Deficiency Treatment Consortium (PIDTC) Survey.

Primary Immune Regulatory Disorders (PIRD) are an expanding group of diseases caused by gene defects in several different immune pathways, such as regulatory T cell function. Patients with PIRD develop clinical manifestations associated with diminished and exaggerated immune responses. Management of these patients is complicated; oftentimes immunosuppressive therapies are insufficient, and patients may require hematopoietic cell transplant (HCT) for treatment. Analysis of HCT data in PIRD patients have previously focused on a single gene defect. This study surveyed transplanted patients with a phenotypic clinical picture consistent with PIRD treated in 33 Primary Immune Deficiency Treatment Consortium centers and European centers. Our data showed that PIRD patients often had immunodeficient and autoimmune features affecting multiple organ systems. Transplantation resulted in resolution of disease manifestations in more than half of the patients with an overall 5-years survival of 67%. This study, the first to encompass disorders across the PIRD spectrum, highlights the need for further research in PIRD management

CONCEPÇÃO E IMPLANTAÇÃO DO NÚCLEO DE INFORMAÇÃO BIOTECNOLÓGICA DO CENTRO DE BIOTECNOLOGIA DA AMAZÔNIA

Aborda o percurso de criação do Núcleo de Informação Biotecnológica (NIB) do Centro de Biotecnologia da Amazônia (CBA) que propôs a prestação de produtos e serviços informacionais com uma gestão integrada de informação e conhecimento como apoio ao desenvolvimento da bioindústria no Brasil. Destaca que o Centro foi delineado com o objetivo de desenvolver novas tecnologias biotecnológicas, para pesquisas integradas na área da biotecnologia, a fim de fornecer suporte às empresas de transformação, industrialização de produtos naturais, formação de empresas de base tecnológica e de recursos humanos. Aponta que tais objetivos exigiram a instituição do Núcleo, o qual pautou suas ações por meio da utilização e geração adequada de fontes, serviços e fornecedores de informação, tanto interna como externa ao Centro, com a função de promover os saberes e transferência de tecnologia. Descreve os produtos e serviços do Núcleo de modo a explorar o seu papel informacional na Região Amazônica. Ressalta a prospecção de 16 produtos e serviços e a efetiva implantação de 26. Conclui que o registro pragmático desta implantação se faz necessário por dois aspectos, a saber: dimensionar o esforço realizado para executar tão importante projeto que se encontra atualmente desamparado pelas políticas públicas brasileiras e para favorecer a implantação de outros no que concerne a poucos modelos existentes. O artigo dispõe sobre a metodologia utilizada e descreve os serviços e produtos como resultado do esforço realizado para implantar o Núcleo

Conception and implementation of the Biotechnology Information Core in the Biotechnology Center of Amazon

Describes the creation of the Biotechnology Information Center (NIB), a section of Amazon Biotechnology Center (CBA), which purpose is to provide informational products and services through a integrated management of knowledge and information in order to support the development brazilian bioindustries. It is important to mention that the Center was designed to develop new technologies in biotechnology field, providing support to process industries, in which it is used natural products as raw material, as well as, to contribute to development of biotechnology-based industries and improve the local human resources. To reach such goals, it is demanded the establishment of the Biotechnology Information Center, which has based its actions through the use and generation of adequate sources, services and supplies of information, both internal and external to the Center, with the task of promoting knowledge and technology transfer. In this article it is described the products and services from Biotechnology Information Center, emphasizing on its own informational role in the Amazon region by the exploration of 16 products and services and the effective implementation of 26. Concludes that the pragmatic record of this establishment is needed for two main aspects: First is to dimension the efforts to start such important project that is currently helpless by the brazilian public policy and to encourage the implementation of others Information centers regarding the few existing models. This article describes the used methodology, the services and products as a result of the achievement of Biotechnology Information Center implementation.Aborda o percurso de criação do Núcleo de Informação Biotecnológica (NIB) do Centro de Biotecnologia da Amazônia (CBA) que propôs a prestação de produtos e serviços informacionais com uma gestão integrada de informação e conhecimento como apoio ao desenvolvimento da bioindústria no Brasil. Destaca que o Centro foi delineado com o objetivo de desenvolver novas tecnologias biotecnológicas, para pesquisas integradas na área da biotecnologia, a fim de fornecer suporte às empresas de transformação, industrialização de produtos naturais, formação de empresas de base tecnológica e de recursos humanos. Aponta que tais objetivos exigiram a instituição do Núcleo, o qual pautou suas ações por meio da utilização e geração adequada de fontes, serviços e fornecedores de informação, tanto interna como externa ao Centro, com a função de promover os saberes e transferência de tecnologia. Descreve os produtos e serviços do Núcleo de modo a explorar o seu papel informacional na Região Amazônica. Ressalta a prospecção de 16 produtos e serviços e a efetiva implantação de 26. Conclui que o registro pragmático desta implantação se faz necessário por dois aspectos, a saber: dimensionar o esforço realizado para executar tão importante projeto que se encontra atualmente desamparado pelas políticas públicas brasileiras e para favorecer a implantação de outros no que concerne a poucos modelos existentes. O artigo dispõe sobre a metodologia utilizada e descreve os serviços e produtos como resultado do esforço realizado para implantar o Núcleo

The genetic landscape of severe combined immunodeficiency in the United States and Canada in the current era (2010-2018).

In a 250 patient cohort from the US and Canada in the current era (2010–2018), we show that over 90% of patients with severe combined immunodeficiency (SCID) can be genetically-characterized

Measuring the effect of newborn screening on survival after haematopoietic cell transplantation for severe combined immunodeficiency: a 36-year longitudinal study from the Primary Immune Deficiency Treatment Consortium

BACKGROUND: Severe combined immunodeficiency (SCID) is fatal unless durable adaptive immunity is established, most commonly through allogeneic haematopoietic cell transplantation (HCT). The Primary Immune Deficiency Treatment Consortium (PIDTC) explored factors affecting the survival of individuals with SCID over almost four decades, focusing on the effects of population-based newborn screening for SCID that was initiated in 2008 and expanded during 2010-18. METHODS: We analysed transplantation-related data from children with SCID treated at 34 PIDTC sites in the USA and Canada, using the calendar time intervals 1982-89, 1990-99, 2000-09, and 2010-18. Categorical variables were compared by χ test and continuous outcomes by the Kruskal-Wallis test. Overall survival was estimated by the Kaplan-Meier method. A multivariable analysis using Cox proportional hazards regression models examined risk factors for HCT outcomes, including the variables of time interval of HCT, infection status and age at HCT, trigger for diagnosis, SCID type and genotype, race and ethnicity of the patient, non-HLA-matched sibling donor type, graft type, GVHD prophylaxis, and conditioning intensity. FINDINGS: For 902 children with confirmed SCID, 5-year overall survival remained unchanged at 72%-73% for 28 years until 2010-18, when it increased to 87% (95% CI 82·1-90·6; n=268; p=0·0005). For children identified as having SCID by newborn screening since 2010, 5-year overall survival was 92·5% (95% CI 85·8-96·1), better than that of children identified by clinical illness or family history in the same interval (79·9% [69·5-87·0] and 85·4% [71·8-92·8], respectively [p=0·043]). Multivariable analysis demonstrated that the factors of active infection (hazard ratio [HR] 2·41, 95% CI 1·56-3·72; p\u3c0·0001), age 3·5 months or older at HCT (2·12, 1·38-3·24; p=0·001), Black or African-American race (2·33, 1·56-3·46; p\u3c0·0001), and certain SCID genotypes to be associated with lower overall survival during all time intervals. Moreover, after adjusting for several factors in this multivariable analysis, HCT after 2010 no longer conveyed a survival advantage over earlier time intervals studied (HR 0·73, 95% CI 0·43-1·26; p=0·097). This indicated that younger age and freedom from infections at HCT, both directly driven by newborn screening, were the main drivers for recent improvement in overall survival. INTERPRETATION: Population-based newborn screening has facilitated the identification of infants with SCID early in life, in turn leading to prompt HCT while avoiding infections. Public health programmes worldwide can benefit from this definitive demonstration of the value of newborn screening for SCID. FUNDING: National Institute of Allergy and Infectious Diseases, Office of Rare Diseases Research, and National Center for Advancing Translational Sciences

The diagnosis of severe combined immunodeficiency: Implementation of the PIDTC 2022 Definitions.

BACKGROUND: Shearer et al in 2014 articulated well-defined criteria for the diagnosis and classification of severe combined immunodeficiency (SCID) as part of the Primary Immune Deficiency Treatment Consortiums (PIDTCs) prospective and retrospective studies of SCID. OBJECTIVE: Because of the advent of newborn screening for SCID and expanded availability of genetic sequencing, revision of the PIDTC 2014 Criteria was needed. METHODS: We developed and tested updated PIDTC 2022 SCID Definitions by analyzing 379 patients proposed for prospective enrollment into Protocol 6901, focusing on the ability to distinguish patients with various SCID subtypes. RESULTS: According to PIDTC 2022 Definitions, 18 of 353 patients eligible per 2014 Criteria were considered not to have SCID, whereas 11 of 26 patients ineligible per 2014 Criteria were determined to have SCID. Of note, very low numbers of autologous T cells (<0.05 × 109/L) characterized typical SCID under the 2022 Definitions. Pathogenic variant(s) in SCID-associated genes was identified in 93% of patients, with 7 genes (IL2RG, RAG1, ADA, IL7R, DCLRE1C, JAK3, and RAG2) accounting for 89% of typical SCID. Three genotypes (RAG1, ADA, and RMRP) accounted for 57% of cases of leaky/atypical SCID; there were 13 other rare genotypes. Patients with leaky/atypical SCID were more likely to be diagnosed at more than age 1 year than those with typical SCID lacking maternal T cells: 20% versus 1% (P < .001). Although repeat testing proved important, an initial CD3 T-cell count of less than 0.05 × 109/L differentiated cases of typical SCID lacking maternal cells from leaky/atypical SCID: 97% versus 7% (P < .001). CONCLUSIONS: The PIDTC 2022 Definitions describe SCID and its subtypes more precisely than before, facilitating analyses of SCID characteristics and outcomes

Measuring the effect of newborn screening on survival after haematopoietic cell transplantation for severe combined immunodeficiency: a 36-year longitudinal study from the Primary Immune Deficiency Treatment Consortium.

BACKGROUND: Severe combined immunodeficiency (SCID) is fatal unless durable adaptive immunity is established, most commonly through allogeneic haematopoietic cell transplantation (HCT). The Primary Immune Deficiency Treatment Consortium (PIDTC) explored factors affecting the survival of individuals with SCID over almost four decades, focusing on the effects of population-based newborn screening for SCID that was initiated in 2008 and expanded during 2010-18. METHODS: We analysed transplantation-related data from children with SCID treated at 34 PIDTC sites in the USA and Canada, using the calendar time intervals 1982-89, 1990-99, 2000-09, and 2010-18. Categorical variables were compared by χ2 test and continuous outcomes by the Kruskal-Wallis test. Overall survival was estimated by the Kaplan-Meier method. A multivariable analysis using Cox proportional hazards regression models examined risk factors for HCT outcomes, including the variables of time interval of HCT, infection status and age at HCT, trigger for diagnosis, SCID type and genotype, race and ethnicity of the patient, non-HLA-matched sibling donor type, graft type, GVHD prophylaxis, and conditioning intensity. FINDINGS: For 902 children with confirmed SCID, 5-year overall survival remained unchanged at 72%-73% for 28 years until 2010-18, when it increased to 87% (95% CI 82·1-90·6; n=268; p=0·0005). For children identified as having SCID by newborn screening since 2010, 5-year overall survival was 92·5% (95% CI 85·8-96·1), better than that of children identified by clinical illness or family history in the same interval (79·9% [69·5-87·0] and 85·4% [71·8-92·8], respectively [p=0·043]). Multivariable analysis demonstrated that the factors of active infection (hazard ratio [HR] 2·41, 95% CI 1·56-3·72; p<0·0001), age 3·5 months or older at HCT (2·12, 1·38-3·24; p=0·001), Black or African-American race (2·33, 1·56-3·46; p<0·0001), and certain SCID genotypes to be associated with lower overall survival during all time intervals. Moreover, after adjusting for several factors in this multivariable analysis, HCT after 2010 no longer conveyed a survival advantage over earlier time intervals studied (HR 0·73, 95% CI 0·43-1·26; p=0·097). This indicated that younger age and freedom from infections at HCT, both directly driven by newborn screening, were the main drivers for recent improvement in overall survival. INTERPRETATION: Population-based newborn screening has facilitated the identification of infants with SCID early in life, in turn leading to prompt HCT while avoiding infections. Public health programmes worldwide can benefit from this definitive demonstration of the value of newborn screening for SCID. FUNDING: National Institute of Allergy and Infectious Diseases, Office of Rare Diseases Research, and National Center for Advancing Translational Sciences

Hematopoietic Cell Transplantation in Patients With Primary Immune Regulatory Disorders (PIRD): A Primary Immune Deficiency Treatment Consortium (PIDTC) Survey.

Primary Immune Regulatory Disorders (PIRD) are an expanding group of diseases caused by gene defects in several different immune pathways, such as regulatory T cell function. Patients with PIRD develop clinical manifestations associated with diminished and exaggerated immune responses. Management of these patients is complicated; oftentimes immunosuppressive therapies are insufficient, and patients may require hematopoietic cell transplant (HCT) for treatment. Analysis of HCT data in PIRD patients have previously focused on a single gene defect. This study surveyed transplanted patients with a phenotypic clinical picture consistent with PIRD treated in 33 Primary Immune Deficiency Treatment Consortium centers and European centers. Our data showed that PIRD patients often had immunodeficient and autoimmune features affecting multiple organ systems. Transplantation resulted in resolution of disease manifestations in more than half of the patients with an overall 5-years survival of 67%. This study, the first to encompass disorders across the PIRD spectrum, highlights the need for further research in PIRD management

ATLANTIC BIRD TRAITS: a data set of bird morphological traits from the Atlantic forests of South America

Scientists have long been trying to understand why the Neotropical region holds the highest diversity of birds on Earth. Recently, there has been increased interest in morphological variation between and within species, and in how climate, topography, and anthropogenic pressures may explain and affect phenotypic variation. Because morphological data are not always available for many species at the local or regional scale, we are limited in our understanding of intra- and interspecies spatial morphological variation. Here, we present the ATLANTIC BIRD TRAITS, a data set that includes measurements of up to 44 morphological traits in 67,197 bird records from 2,790 populations distributed throughout the Atlantic forests of South America. This data set comprises information, compiled over two centuries (1820–2018), for 711 bird species, which represent 80% of all known bird diversity in the Atlantic Forest. Among the most commonly reported traits are sex (n = 65,717), age (n = 63,852), body mass (n = 58,768), flight molt presence (n = 44,941), molt presence (n = 44,847), body molt presence (n = 44,606), tail length (n = 43,005), reproductive stage (n = 42,588), bill length (n = 37,409), body length (n = 28,394), right wing length (n = 21,950), tarsus length (n = 20,342), and wing length (n = 18,071). The most frequently recorded species are Chiroxiphia caudata (n = 1,837), Turdus albicollis (n = 1,658), Trichothraupis melanops (n = 1,468), Turdus leucomelas (n = 1,436), and Basileuterus culicivorus (n = 1,384). The species recorded in the greatest number of sampling localities are Basileuterus culicivorus (n = 243), Trichothraupis melanops (n = 242), Chiroxiphia caudata (n = 210), Platyrinchus mystaceus (n = 208), and Turdus rufiventris (n = 191). ATLANTIC BIRD TRAITS (ABT) is the most comprehensive data set on measurements of bird morphological traits found in a biodiversity hotspot; it provides data for basic and applied research at multiple scales, from individual to community, and from the local to the macroecological perspectives. No copyright or proprietary restrictions are associated with the use of this data set. Please cite this data paper when the data are used in publications or teaching and educational activities. © 2019 The Authors. Ecology © 2019 The Ecological Society of Americ