Abstract
Introduction
The PIDBioRep establishment resulted in facility remodeling and equipment purchases as well as training staff to receive, prepare, and store samples. Biological samples are stored in cryotubes with barcodes and different color caps according to sample type, and standard kits are used to isolate genomic DNA and RNA from peripheral blood.
The partnership with the Medical Informatics Laboratory team from A.C. Camargo Hospital allowed the Children's Hospital to customize and use the software in the hospital server, which can be accessed through the internal network. Systems installed are as follows: i) LOGIN - fits all systems, its main functions include management of people (register and permissions), rules, domains, messages and modification of user information, including passwords; ii) BIOBANK - registers and oversees tissues and blood samples; collections linked to projects; containers and freezers; procedures for RNA, DNA and protein extraction; applications made by researchers; storage, removal and disposal of samples and administration of all samples history; iii) XUSD – centralizes and manages structured models, defines which models users may access, fills in models already indexed, stores information in a structured form, searches information in models, imports data from another database and exports data to a file with a CSV extension.
All patients have their medical records reviewed, and a structured protocol is completed in order to create the clinical-laboratory database. Parents or care providers respond to a questionnaire regarding a patient's personal medical history and presence of other family members with autoimmune disease and/or primary immunodeficiency. During this time, laboratory tests for autoantibodies and reports of lifestyles, events or emotional changes that parents or care providers consider possible triggers to autoimmune disease are recorded. Questionnaires are transferred to XUSD. Once informed consent is obtained and the clinical-laboratory protocol is completed, whole blood samples are sent for cryopreservation and storage of serum, plasma, DNA and, depending on the active line of research, RNA, urine, tissue samples, breast milk or mononuclear cells are also stored at the Laboratory for Medical Research (LIM-36) at Children's Hospital. To guarantee adequate processing and storage of samples, standard technical procedures have been established based on the quality management system BIOBANK. While biological sample collection is being conducted, BIOBANK software links with the clinical-laboratory database, turning the biorepository into a complete tool to make full use of these samples. The link between biological samples and patients' clinical-laboratory data are maintained so that a patient may be contacted to obtain additional samples. The researcher who gains access to specimens receives only the sample number, which provides protection for patient confidentiality throughout the entire process. All institutional researchers can send forms and request samples from the scientific committee.
The clinical-laboratory database and biorepository have promoted advances in clinical research as well as facilitated both molecular investigation of common genetic bases of autoimmune diseases and a better understanding of frequencies, associations and modes of inheritance of these disorders. The facility is currently participating in a thematic project and gives support for ongoing research initiatives, especially properly storing serum and DNA for future analyses. In addition, researchers have used clinical-laboratory information and human biological samples collected by this facility, resulting in a series of works.3,4,8–15
Therefore, as a pioneer initiative, this clinical-laboratory database and biorepository will supply researchers with important information and an apparatus that can illuminate the causative factors of autoimmune diseases and primary immunodeficiencies.
E-mail: bernadete.liphaus@hc.fm.usp.br or magdascs@usp.br
Instituto da Criança, LIM-36, telephone 55-11-26618606
Bernadete L Liphaus, MD, PhD or
Magda Carneiro-Sampaio, MD, PhD
Institution core budget: 10 %
Grants: 90 %
Overall response to consent: In accordance with Brazil's regulations regarding the storage and use of human biological materials for research, all (100%) participants give written consent before any sample is sent to the biorepository.
Total individual cases held: 256
100 % cases associated with blood biospecimens: 302 sera samples, 312 plasma samples and 365 DNA samples
The clinical-laboratory database and biorepository value has effectively been demonstrated by its participation—giving support for ongoing projects, especially thematic research in autoimmunity and immunodeficiencies, and a series of dissertations, theses and published articles from work performed at our facility. Approximately 70 biospecimens and 26 cases were released this year (2013). Since the clinical-laboratory database and biorepository was established it has collaborated on 44 presented abstracts, two dissertations, three theses, eight published articles and five ongoing research projects.3,4,8–15
As a research infrastructure and center of competence, we believe that our pediatric population provides a unique opportunity to study genetic factors involved in reducing tolerance with minimal influence of environmental factors. Furthermore, primary immunodeficiencies may represent special human models for unraveling components of pathogenesis of autoimmune diseases, as there are immunodeficiencies that are systematically associated with autoimmunity.
One major challenge is maintenance of organizational structure of the clinical-laboratory database and biorepository that is based on three points: compliance with legislation, a formal process to record and access clinical data, and standardized technical procedures for collecting and storing samples. Another major challenge is keeping the trust and collaboration among multiple institutional research teams with various types of expertise. The establishment of an institutional database and biorepository requires the ability to involve different professionals and to allocate long-term resources and labor time. Likewise, effectively designing a database necessitates a user-friendly platform that will return the largest possible amount of clinical information. One additional challenge when creating a patient-based biorepository is ensuring that participants are adequately informed about the purposes of storing samples and possible future uses of the collection. Furthermore, biobanking is not an end in itself and to prove its value, the collected samples must be used in research projects that result in gain of knowledge of diseases being studied, which eventually will lead to development of new treatments, diagnostic and prevention methods.
1. Invest in training staff (laboratory technologist, research nurse and data manager) to collect standardized clinical and laboratory information as well as to receive, prepare and store samples; 2. Train a professional at Children's Hospital Service of Technology and Information in Health to help with further software maintenance and customization; 3. Establish an appropriate technique for preserving cell lineages from patients with well-defined primary immunodeficiencies and identify gene mutations; 4. Obtain a large and high-quality DNA collection to promote epidemiological genetic studies in Brazil; 5. Include samples from patients all over the country participating in the CoBID.
Footnotes
Acknowledgments
The authors acknowledge Diogo F.C. Patrão, Joyce M.A. Reis, Fernanda A.M. Fonseca, Luiz P. Camargo, Fernando Camargo, and Francisco Costa-Neto for their contribution on systems installation and adaptation, data acquisition, and smple storing.