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Previous issue date: 2013-03-05 / Introduction: Antiphospholipid syndrome (APS) is characterized by venous or arterial thromboses, fetal losses and thrombocytopenia, in the presence of antiphospholipid antibodies (aPL). CD4+CD25+Foxp3+ regulatory T (Treg) cell dysfunction has been documented in various autoimmune disorders, but not in antiphospholipid syndrome (APS) up to date. Methods: In this cross-sectional study, we aim to investigate CD4+CD25+Foxp3+ Treg cells and CD3 CD19+ B cells in patients with primary APS, APS secondary to systemic lupus erythematosus (SLE) and healthy controls. Cell subtypes were immunophenotyped using specific monoclonal antibodies (anti-CD3 CY5, anti-CD4 FITC, anti-CD25, anti-Foxp3, anti-CD19 PE) and flow cytometry. Results: Twenty and five patients with primary APS, 25 with APS secondary to SLE and 25 age- and sexmatched controls were studied. The percentage Treg cells and CD3 CD19+ B cells were found significantly lower in primary APS and APS secondary to SLE patients as compared to controls (all p < 0.05). Decreasing levels of circulating Treg cells correlated to higher scores of lupus activity (r=-0.75, p<0.0001). Number of circulating Treg cells did not significantly vary among users or nonusers of chloroquine, azathioprine and corticosteroids (p=0.90, p=0.76 and p=0.29, respectively). Conclusion: A dysfunction in CD4+CD25+Foxp3+ Treg cells may represent one of the mechanisms leading to autoimmunity in APS patients. The decreased number of CD3 CD19+ B cells of APS patients warrants further elucidation. / Introdu??o: A s?ndrome antifosfolip?dica (SAF) ? uma trombofilia autoimune caracterizada por trombose arterial e/ou venosa, morbidade gestacional e presen?a de anticorpos antifosfol?pides. As c?lulas T reguladoras (Treg) CD4+CD25+FoxP3+ desempenham importante papel no controle supressivo da resposta imune, sendo sua hipofun??o associada ? autoimunidade. Por sua vez, os linf?citos B, al?m de se comportarem como c?lulas autorreativas, podem deflagrar a produ??o de c?lulas Treg. Objetivo: Quantificar, originalmente, c?lulas Treg CD4+CD25+FoxP3+ e linf?citos B CD3-CD19+ em pacientes com SAF prim?ria e secund?ria comparativamente a controles sadios. Materiais e m?todos: O estudo, transversal controlado, incluiu a an?lise fenot?pica de c?lulas mononucleares de sangue perif?rico nos tr?s grupos de indiv?duos acima mencionados; as c?lulas foram marcadas com anticorpos monoclonais contra CD4 FITH, CD25 APC, FoxP3 PE, CD3 CY5 e CD19 PE e quantificadas por citometria de fluxo. Resultados: Vinte e cinco pacientes com SAF prim?ria, 25 com SAF secund?ria a l?pus eritematoso pareados por sexo e idade e 25 controles sadios participaram deste estudo. O valor encontrado, percentual e absoluto, de c?lulas CD4+CD25+FoxP3+ e de c?lulas B CD3-CD19+ nos pacientes com SAF prim?ria foi significativamente menor quando comparados a controles sadios (P<0,05). No grupo com SAF secund?ria, as c?lulas CD4+CD25+FoxP3+ e CD3-CD19+ tamb?m estiveram significativamente diminu?das em rela??o aos controles (P<0,05). O teste de Pearson revelou correla??o negativa entre n?mero de c?lulas CD4+CD25+FoxP3+ e SLEDAI em pacientes com SAF secund?ria (rS=-0,75, P<0,05); n?o houve associa??o entre n?mero de c?lulas Treg e uso de azatioprina (P=0,23), glicocortic?ides (P= 0,29) e cloroquina (P=0,12). Conclus?o: Pacientes com SAF prim?ria ou secund?ria tiveram definida deple??o de c?lulas Treg CD4+CD25+FoxP3+, o que pode ter contribu?do para os fen?menos autoimunes vistos na doen?a. A diminui??o do n?mero de c?lulas B CD3-CD19+ nestes pacientes deve ser elucidada em estudos futuros.
| Identifer | oai:union.ndltd.org:IBICT/oai:tede2.pucrs.br:tede/1729 |
| Date | 05 March 2013 |
| Creators | Dal Ben, Ester Ros?ri Raphaelli |
| Contributors | Staub, Henrique Luiz |
| Publisher | Pontif?cia Universidade Cat?lica do Rio Grande do Sul, Programa de P?s-Gradua??o em Medicina e Ci?ncias da Sa?de, PUCRS, BR, Faculdade de Medicina |
| Source Sets | IBICT Brazilian ETDs |
| Language | Portuguese |
| Detected Language | Unknown |
| Type | info:eu-repo/semantics/publishedVersion, info:eu-repo/semantics/doctoralThesis |
| Format | application/pdf |
| Source | reponame:Biblioteca Digital de Teses e Dissertações da PUC_RS, instname:Pontifícia Universidade Católica do Rio Grande do Sul, instacron:PUC_RS |
| Rights | info:eu-repo/semantics/openAccess |
| Relation | 7620745074616285884, 500, 600, 8624664729441623247 |
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