BIOBANK PROFILE
BIOPRESERVATION AND BIOBANKING Volume 11, Number 5, 2013 ª Mary Ann Liebert, Inc. DOI: 10.1089/bio.2013.1153
Pediatric Immunological Disorders Biorepository (PIDBioRep) at University of Sa˜o Paulo Medical School, Brazil Introduction
T
he Pediatric Immunological Disorders Biorepository (PIDBioRep) is a clinical-laboratory database and biorepository with an open-ended prospective patient-based cohort, located at the University of Sa˜o Paulo Medical School (FMUSP- Faculdade de Medicina da Universidade de Sa˜o Paulo) Children’s Hospital in Brazil. Its purpose was to set up an infrastructure for research on pediatric immunological disorders, particularly early-onset autoimmune diseases and primary immunodeficiencies. Participants are being recruited from all of the hospital specialty divisions that currently comprise an estimated cohort of 1,200 infants, children, and adolescents with diagnoses of organ-specific and systemic autoimmune diseases and 300 patients with well-defined primary immunodeficiencies. The PIDBioRep complies Brazil’s regulations regarding the use and storage of biological samples.1,2,5,6,7 The ethical committee of our hospital approved the informed consent form that is provided to each patient. 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 auto-
immune 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. Title of biobank: Pediatric Immunological Disorders Biorepository (PIDBioRep) at University of Sa˜o Paulo Medical School, Brazil Site location: University of Sa˜o Paulo Medical School, Children’s Hospital, LIM-36, Sa˜o Paulo, Brazil
324
BIOBANK PROFILE Contact information: E-mail: [email protected] or [email protected] Instituto da Crianc¸a, LIM-36, telephone 55-11-26618606 Bernadete L Liphaus, MD, PhD or Magda Carneiro-Sampaio, MD, PhD Date of operations: December 2009 Date range of cases: December 2009 to present Category of biobank: Basic/Translational/Epidemiological/ Clinical Focus of biobank: Clinical-laboratory data and longitudinal top-quality collection of several types of samples exclusively from pediatric cohorts of patients and age-matched healthy volunteers. Specifically, the collection includes infants, children and adolescents with early-onset diagnoses of organspecific and systemic autoimmune diseases, including juvenile systemic lupus erythematosus, juvenile idiopathic arthritis, juvenile dermatomyositis, type 1 diabetes mellitus, thyroiditis, celiac disease, inflammatory bowel disease, immune thrombocytopenic purpura and autoimmune hepatitis. The collection also includes samples from infants and children with diagnoses of auto-inflammatory diseases and 62 different well-defined primary immunodeficiencies. Membership of biobank: Clinical and research staff from Children’s Hospital, including allergy and immunology, clinical genetic, endocrinology, gastroenterology, hematology and rheumatology divisions and the Brazilian Consortium for Reference and Training in Primary Immunodeficiencies (CoBID). Major source of funding: Sa˜o Paulo Research Foundation grant (FAPESP-Fundac¸a˜o de Amparo a` Pesquisa do Estado de Sa˜o Paulo, 2008-58238-4) and Children’s Hospital institutional financial support. Proportional funding sources for biobank: Institution core budget: 10 % Grants: 90 % Example input statistics: 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 Example output statistics: 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 clinicallaboratory database and biorepository was established it has collaborated on 44 presented abstracts, two dissertations,
325 three theses, eight published articles and five ongoing research projects.3,4,8–15 What are the most valuable/highest priority cases in your biobank? 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. What are your major challenges? 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. What would you do with $1 million to improve the value of your biobank: 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.
Acknowledgments The authors acknowledge Diogo F.C. Patra˜o, 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.
326
BIOBANK PROFILE
References 1. Ministe´rio da Sau´de do Brasil. Diretrizes Nacionais para Biorreposito´rio e Biobanco de Material Biolo´gico Humano com Finalidade de Pesquisa. Portaria No 2.201, de 14 de Setembro de 2011. Available at http://www2.inca.gov.br/wps/wcm/connect/ 59b03d 80485acdbc8570b563a415c33e/portaria_2201_de_14_de_set_ 2011.pdf?MOD = AJPERES&CACHEID = 59b00d80485acdbc8570 b563a415c32e. 2. Comissa˜o Nacional de E´tica em Pesquisa do Conselho Nacional de Sau´de, Brasil. Resoluc¸a˜o CNS 441/11 sobre armazenamento de material biolo´gico humano com finalidade de pesquisa. Available at http://conselho.saude.gov.br/resolucoes/2011/Reso441 .pdf. 3. Carneiro-Sampaio M, Liphaus BL, Jesus AA, Silva CAA, Oliveira JB, Kiss MHB. Undertanding systemic lupus erythematosus physiopathology in light of primary immunodeficiencies. J Clin Immunol 2008;28:S34–S41. 4. Carneiro-Sampaio M, Coutinho A. Tolerance and autoimmunity: Lessons at the bedside of primary immunodeficiencies. Adv Immunol 2007;95:51–82. 5. Campbell JD, Skubitz APN, Somiari SB, et al. International Society for Biological and Environmental Repositories (ISBER) 2008 Best practices for repositories: Collection, storage, retrieval and distribution of biological materials for research. Cell Preserv Technol 2008;6:3–58. 6. Hospital A C Camargo. Fundac¸a˜o Antoˆnio Prudente. Banco de Tumores. Available at http://www.accamargo. org.br/bancode-tumores. 7. Campos AHJFM, Silva AA, Mota LDC, Olivieri ER, Prescinoti VC, Patra˜o D, Camargo LP, Brentani H, Carraro DM, Brentani RR, Soares FA. The value of a tumor bank in the development of cancer research in Brazil: 13 years of experience at the AC Camargo Hospital. Biopreserv Biobank 2012;10:168–173. 8. Jesus AA, Silva CA, Carneiro-Sampaio M, Sheinberg M, Mangueira CL, Marie SK, Liphaus BL. Anti-C1q antibodies in juvenile-onset systemic lupus erythematosus. Ann NY Acad Sci 2009;1173:235–238. 9. Jesus AA, Liphaus BL, Silva CA, Bando S, Andrade LEC, Coutinho A, Carneiro-Sampaio M. Complement and antibody primary immunodeficiency in juvenile systemic lupus erythematosus patients. Lupus 2011; 20:1275–1284. 10. Umetsu N, Liphaus BL, Bando S, Jesus AA, Carneiro-Sampaio M. Silent Mutations and Polymorphisms in the 5’UTR and
11.
12.
13.
14.
15.
3’UTR of C1QB Gene in a Brazilian Patient with Juvenile Systemic Lupus Erythematosus ( JSLE). Ann Rheum Dis (Suppl). 2011;70:24. Liphaus BL, Jesus AA, Silva CA, Coutino A, Carneiro-Sampaio M. Increased IgE serum levels are unrelated to allergic and parasitic diseases in patients with juvenile systemic lupus erythematosus. Clinics 2012; 67:1275–1280. Jesus AA, Campos LMA, Liphaus BL, Carneiro-Sampaio M, Mangueira CL, Rosseto E, Silva CA, Scheinberg M. Anti-C1q, anti-chromatin/nucleosome, and anti-DNA antibodies in juvenile systemic lupus erythematosus patients. Rev Bras Reumatol 2012;52:971–981. Andrade LEC, Pereira KMC, Faria AGA, Liphaus BL, Jesus AA, Silva CA, Carneiro-Sampaio M. Low gene copy number for C4, C4A, C4B is a strong risk factor for developing systemic lupus erythematosus in childhood. Arthritis Rheum 2012;64:2282. Liphaus BL, Umetsu N, Bando S, Jesus AA, Andrade LEC, Silva CA, Carneiro-SampaioM. Molecular characterization of complement C1q, C2, and C4 genes in juvenile systemic lupus erythematosus. Ann Rheum Dis 2013;72:727. Aikawa NE, Jesus AA, Liphaus BL, Silva CA, Carneiro-Sampaio M, Viana VT, Sallum AME. Organ-specific autoantibodies and autoimmune diseases in juvenile systemic lupus erythematosus and juvenile dermatomyisistis patients. Clin Exp Rheumatol 2012;30:126–131.
Address correspondence to: Bernadete L Liphaus, MD, PhD Magda Carneiro-Sampaio, MD, PhD PIDBioRep Instituto da Crianc¸a Av. Dr. Eneas de Carvalho Aguiar 647 5 andar, LIM-36 Cerqueira Cesar Sa˜o Paulo–SP Brazil CEP 05403-900 E-mail: [email protected] [email protected]
BIOPRESERVATION AND BIOBANKING Volume 11, Number 5, 2013 ª Mary Ann Liebert, Inc. DOI: 10.1089/bio.2013.1153
Pediatric Immunological Disorders Biorepository (PIDBioRep) at University of Sa˜o Paulo Medical School, Brazil Introduction
T
he Pediatric Immunological Disorders Biorepository (PIDBioRep) is a clinical-laboratory database and biorepository with an open-ended prospective patient-based cohort, located at the University of Sa˜o Paulo Medical School (FMUSP- Faculdade de Medicina da Universidade de Sa˜o Paulo) Children’s Hospital in Brazil. Its purpose was to set up an infrastructure for research on pediatric immunological disorders, particularly early-onset autoimmune diseases and primary immunodeficiencies. Participants are being recruited from all of the hospital specialty divisions that currently comprise an estimated cohort of 1,200 infants, children, and adolescents with diagnoses of organ-specific and systemic autoimmune diseases and 300 patients with well-defined primary immunodeficiencies. The PIDBioRep complies Brazil’s regulations regarding the use and storage of biological samples.1,2,5,6,7 The ethical committee of our hospital approved the informed consent form that is provided to each patient. 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 auto-
immune 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. Title of biobank: Pediatric Immunological Disorders Biorepository (PIDBioRep) at University of Sa˜o Paulo Medical School, Brazil Site location: University of Sa˜o Paulo Medical School, Children’s Hospital, LIM-36, Sa˜o Paulo, Brazil
324
BIOBANK PROFILE Contact information: E-mail: [email protected] or [email protected] Instituto da Crianc¸a, LIM-36, telephone 55-11-26618606 Bernadete L Liphaus, MD, PhD or Magda Carneiro-Sampaio, MD, PhD Date of operations: December 2009 Date range of cases: December 2009 to present Category of biobank: Basic/Translational/Epidemiological/ Clinical Focus of biobank: Clinical-laboratory data and longitudinal top-quality collection of several types of samples exclusively from pediatric cohorts of patients and age-matched healthy volunteers. Specifically, the collection includes infants, children and adolescents with early-onset diagnoses of organspecific and systemic autoimmune diseases, including juvenile systemic lupus erythematosus, juvenile idiopathic arthritis, juvenile dermatomyositis, type 1 diabetes mellitus, thyroiditis, celiac disease, inflammatory bowel disease, immune thrombocytopenic purpura and autoimmune hepatitis. The collection also includes samples from infants and children with diagnoses of auto-inflammatory diseases and 62 different well-defined primary immunodeficiencies. Membership of biobank: Clinical and research staff from Children’s Hospital, including allergy and immunology, clinical genetic, endocrinology, gastroenterology, hematology and rheumatology divisions and the Brazilian Consortium for Reference and Training in Primary Immunodeficiencies (CoBID). Major source of funding: Sa˜o Paulo Research Foundation grant (FAPESP-Fundac¸a˜o de Amparo a` Pesquisa do Estado de Sa˜o Paulo, 2008-58238-4) and Children’s Hospital institutional financial support. Proportional funding sources for biobank: Institution core budget: 10 % Grants: 90 % Example input statistics: 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 Example output statistics: 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 clinicallaboratory database and biorepository was established it has collaborated on 44 presented abstracts, two dissertations,
325 three theses, eight published articles and five ongoing research projects.3,4,8–15 What are the most valuable/highest priority cases in your biobank? 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. What are your major challenges? 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. What would you do with $1 million to improve the value of your biobank: 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.
Acknowledgments The authors acknowledge Diogo F.C. Patra˜o, 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.
326
BIOBANK PROFILE
References 1. Ministe´rio da Sau´de do Brasil. Diretrizes Nacionais para Biorreposito´rio e Biobanco de Material Biolo´gico Humano com Finalidade de Pesquisa. Portaria No 2.201, de 14 de Setembro de 2011. Available at http://www2.inca.gov.br/wps/wcm/connect/ 59b03d 80485acdbc8570b563a415c33e/portaria_2201_de_14_de_set_ 2011.pdf?MOD = AJPERES&CACHEID = 59b00d80485acdbc8570 b563a415c32e. 2. Comissa˜o Nacional de E´tica em Pesquisa do Conselho Nacional de Sau´de, Brasil. Resoluc¸a˜o CNS 441/11 sobre armazenamento de material biolo´gico humano com finalidade de pesquisa. Available at http://conselho.saude.gov.br/resolucoes/2011/Reso441 .pdf. 3. Carneiro-Sampaio M, Liphaus BL, Jesus AA, Silva CAA, Oliveira JB, Kiss MHB. Undertanding systemic lupus erythematosus physiopathology in light of primary immunodeficiencies. J Clin Immunol 2008;28:S34–S41. 4. Carneiro-Sampaio M, Coutinho A. Tolerance and autoimmunity: Lessons at the bedside of primary immunodeficiencies. Adv Immunol 2007;95:51–82. 5. Campbell JD, Skubitz APN, Somiari SB, et al. International Society for Biological and Environmental Repositories (ISBER) 2008 Best practices for repositories: Collection, storage, retrieval and distribution of biological materials for research. Cell Preserv Technol 2008;6:3–58. 6. Hospital A C Camargo. Fundac¸a˜o Antoˆnio Prudente. Banco de Tumores. Available at http://www.accamargo. org.br/bancode-tumores. 7. Campos AHJFM, Silva AA, Mota LDC, Olivieri ER, Prescinoti VC, Patra˜o D, Camargo LP, Brentani H, Carraro DM, Brentani RR, Soares FA. The value of a tumor bank in the development of cancer research in Brazil: 13 years of experience at the AC Camargo Hospital. Biopreserv Biobank 2012;10:168–173. 8. Jesus AA, Silva CA, Carneiro-Sampaio M, Sheinberg M, Mangueira CL, Marie SK, Liphaus BL. Anti-C1q antibodies in juvenile-onset systemic lupus erythematosus. Ann NY Acad Sci 2009;1173:235–238. 9. Jesus AA, Liphaus BL, Silva CA, Bando S, Andrade LEC, Coutinho A, Carneiro-Sampaio M. Complement and antibody primary immunodeficiency in juvenile systemic lupus erythematosus patients. Lupus 2011; 20:1275–1284. 10. Umetsu N, Liphaus BL, Bando S, Jesus AA, Carneiro-Sampaio M. Silent Mutations and Polymorphisms in the 5’UTR and
11.
12.
13.
14.
15.
3’UTR of C1QB Gene in a Brazilian Patient with Juvenile Systemic Lupus Erythematosus ( JSLE). Ann Rheum Dis (Suppl). 2011;70:24. Liphaus BL, Jesus AA, Silva CA, Coutino A, Carneiro-Sampaio M. Increased IgE serum levels are unrelated to allergic and parasitic diseases in patients with juvenile systemic lupus erythematosus. Clinics 2012; 67:1275–1280. Jesus AA, Campos LMA, Liphaus BL, Carneiro-Sampaio M, Mangueira CL, Rosseto E, Silva CA, Scheinberg M. Anti-C1q, anti-chromatin/nucleosome, and anti-DNA antibodies in juvenile systemic lupus erythematosus patients. Rev Bras Reumatol 2012;52:971–981. Andrade LEC, Pereira KMC, Faria AGA, Liphaus BL, Jesus AA, Silva CA, Carneiro-Sampaio M. Low gene copy number for C4, C4A, C4B is a strong risk factor for developing systemic lupus erythematosus in childhood. Arthritis Rheum 2012;64:2282. Liphaus BL, Umetsu N, Bando S, Jesus AA, Andrade LEC, Silva CA, Carneiro-SampaioM. Molecular characterization of complement C1q, C2, and C4 genes in juvenile systemic lupus erythematosus. Ann Rheum Dis 2013;72:727. Aikawa NE, Jesus AA, Liphaus BL, Silva CA, Carneiro-Sampaio M, Viana VT, Sallum AME. Organ-specific autoantibodies and autoimmune diseases in juvenile systemic lupus erythematosus and juvenile dermatomyisistis patients. Clin Exp Rheumatol 2012;30:126–131.
Address correspondence to: Bernadete L Liphaus, MD, PhD Magda Carneiro-Sampaio, MD, PhD PIDBioRep Instituto da Crianc¸a Av. Dr. Eneas de Carvalho Aguiar 647 5 andar, LIM-36 Cerqueira Cesar Sa˜o Paulo–SP Brazil CEP 05403-900 E-mail: [email protected] [email protected]
