Browsing by Author "Viana, J."
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- Low frequency of CD4+CD25+ Treg in SLE patients: a heritable trait associated with CTLA4 and TGFbeta gene variants.Publication . Barreto, M.; Ferreira, R.; Lourenço, L.; Moraes-Fontes, M.; Santos, E.; Alves, M.; Carvalho, C.; Martins, B.; Andreia, R.; Viana, J.; Vasconcelos, C.; Mota-Vieira, L.; Ferreira, C.; Demengeot, J.; Vicente, A.Abstract BACKGROUND: CD4+CD25+ regulatory T cells play an essential role in maintaining immune homeostasis and preventing autoimmunity. Therefore, defects in Treg development, maintenance or function have been associated with several human autoimmune diseases including Systemic Lupus Erythematosus (SLE), a systemic autoimmune disease characterized by loss of tolerance to nuclear components and significantly more frequent in females. RESULTS: To investigate the involvement of Treg in SLE pathogenesis, we determined the frequency of CD4+CD25+CD45RO+ T cells, which encompass the majority of Treg activity, in the PBMC of 148 SLE patients (76 patients were part of 54 families), 166 relatives and 117 controls. SLE patients and their relatives were recruited in several Portuguese hospitals and through the Portuguese Lupus Association. Control individuals were blood donors recruited from several regional blood donor centers. Treg frequency was significantly lower in SLE patients than healthy controls (z = -6.161, P < 0.00001) and intermediate in the relatives' group. Remarkably, this T cell subset was also lower in females, most strikingly in the control population (z = 4.121, P < 0.001). We further ascertained that the decreased frequency of Treg in SLE patients resulted from the specific reduction of bona fide FOXP3+CD4+CD25+ Treg. Treg frequency was negatively correlated with SLE activity index (SLEDAI) and titers of serum anti-dsDNA antibodies. Both Treg frequency and disease activity were modulated by IVIg treatment in a documented SLE case. The segregation of Treg frequency within the SLE families was indicative of a genetic trait. Candidate gene analysis revealed that specific variants of CTLA4 and TGFbeta were associated with the decreased frequency of Treg in PBMC, while FOXP3 gene variants were associated with affection status, but not with Treg frequency. CONCLUSION: SLE patients have impaired Treg production or maintenance, a trait strongly associated with SLE disease activity and autoantibody titers, and possibly resulting from the inability to convert FOXP3+CD25- into FOXP3+CD25+ T cells. Treg frequency is highly heritable within SLE families, with specific variants of the CTLA4 and TGFbeta genes contributing to this trait, while FOXP3 contributes to SLE through mechanisms not involving a modulation of Treg frequency. These findings establish that the genetic components in SLE pathogenesis include genes related to Treg generation or maintenance.
- The Portuguese Severe Asthma Registry: Development, Features, and Data Sharing PoliciesPublication . Sá-Sousa, A.; Fonseca, J.; Pereira, A.; Ferreira, A.; Arrobas, A.; Mendes, A.; Drummond, M.; Videira, W.; Costa, T.; Farinha, P.; Soares, J.; Rocha, P.; Todo-Bom, A.; Sokolova, A.; Costa, A.; Fernandes, B.; Chaves Loureiro, C.; Longo, C.; Pardal, C.; Costa, C.; Cruz, C.; Loureiro, C.; Lopes, C.; Mesquita, D.; Faria, E.; Magalhães, E.; Menezes, F.; Todo-Bom, F.; Carvalho, F.; Regateiro, F.; Falcao, H.; Fernandes, I.; Gaspar-Marques, J.; Viana, J.; Ferreira, J.; Silva, J.; Simão, L.; Almeida, L.; Fernandes, L.; Ferreira, L.; van Zeller, M.; Quaresma, M.; Castanho, M.; André, N.; Cortesão, N.; Leiria-Pinto, P.; Pinto, P.; Rosa, P.; Carreiro-Martins, P.; Gerardo, R.; Silva, R.; Lucas, S.; Almeida, T.; Calvo, T.The Portuguese Severe Asthma Registry (Registo de Asma Grave Portugal, RAG) was developed by an open collaborative network of asthma specialists. RAG collects data from adults and pediatric severe asthma patients that despite treatment optimization and adequate management of comorbidities require step 4/5 treatment according to GINA recommendations. In this paper, we describe the development and implementation of RAG, its features, and data sharing policies. The contents and structure of RAG were defined in a multistep consensus process. A pilot version was pretested and iteratively improved. The selection of data elements for RAG considered other severe asthma registries, aiming at characterizing the patient's clinical status whilst avoiding overloading the standard workflow of the clinical appointment. Features of RAG include automatic assessment of eligibility, easy data input, and exportable data in natural language that can be pasted directly in patients' electronic health record and security features to enable data sharing (among researchers and with other international databases) without compromising patients' confidentiality. RAG is a national web-based disease registry of severe asthma patients, available at asmagrave.pt. It allows prospective clinical data collection, promotes standardized care and collaborative clinical research, and may contribute to inform evidence-based healthcare policies for severe asthma.