SOLANGE CARRASCO
Projetos de Pesquisa
Unidades Organizacionais
Departamento de Clínica Médica, Faculdade de Medicina
LIM/17 - Laboratório de Investigação em Reumatologia, Hospital das Clínicas, Faculdade de Medicina
LIM/17 - Laboratório de Investigação em Reumatologia, Hospital das Clínicas, Faculdade de Medicina
2 resultados
Resultados de Busca
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- Circulating Follicular Helper-Like T Cells in Systemic Lupus Erythematosus(2015) CHOI, Jin-Young; HO, John Hsi-en; PASOTO, Sandra G.; BUNIN, Viviane; KIM, Sang Taek; CARRASCO, Solange; BORBA, Eduardo F.; GONCALVES, Celio R.; COSTA, Priscila R.; KALLAS, Esper G.; BONFA, Eloisa; CRAFT, JosephObjective. To assess circulating follicular helper T (Tfh)-like CD4+ T cells in patients with systemic lupus erythematosus (SLE) and determine their relationship to disease activity. Methods. Blood samples from patients with SLE, as well as blood samples from patients with Behcet's disease (BD) and healthy individuals as controls, were analyzed. In all samples, circulating Tfh-like cells were enumerated by flow cytometry, using, as markers, expression of CXCR5, inducible T cell costimulator (ICOS), and programmed death 1 (PD-1) protein, as well as secretion of interleukin-21 (IL-21). The frequency of circulating Tfh-like cells was compared to that of circulating plasmablasts (CD19+IgD-CD38+). In addition, the possible association of circulating Tfh-like cells with the SLE Disease Activity Index (SLEDAI) was evaluated. Results. The subset of circulating Tfh-like T cells, identified as CXCR5(high)ICOS(high)PD-1(high), was expanded in the blood of SLE patients compared to controls. Circulating Tfh-like cells were found to produce IL-21 and had lower expression of CCR7 as compared to that in circulating CXCR5(high) central memory T cells, thereby enabling their distinction. Expression of PD-1, but not ICOS or CXCR5, was significantly elevated in circulating Tfh-like cells from SLE patients compared to controls. PD-1 expression among CXCR5(high) circulating Tfh-like cells correlated with the SLEDAI, frequency of circulating plasmablasts, and anti-double-stranded DNA antibody positivity, but not with disease duration or past organ injury; rather, this cell profile appeared to be a reflection of current active disease. Conclusion. Circulating Tfh-like cells are associated with disease activity in SLE, suggesting that their presence indicates abnormal homeostasis of T cell-B cell collaboration, with a causal relationship that is central to disease pathogenesis. These findings also suggest that circulating Tfh-like cells provide a surrogate for aberrant germinal center activity in SLE, and that their PD-1 expression offers a tool for measuring disease activity and monitoring the response to therapies.
conferenceObject Altered Circulating Follicular Helper T Cell Phenotype and Subset Composition Are Associated with Disease Activity in Patients with Systemic Lupus Erythematosus(2012) HO, Hsi-en; CHOI, Jin Young; BUNIN, Viviane M.; PASOTO, Sandra G.; CARRASCO, Solange; BORBA, Eduardo F.; GONCALVES, Celio R.; COSTA, Priscila R.; KALLAS, Esper G.; BONFA, Eloisa; CRAFT, Joseph E.Background/Purpose: Autoreactive B cells in SLE undergo autoantigen selection, suggesting a requirement for germinal center follicular helper T (Tfh) cells in their maturation. However, evidence for dysregulation of Tfh cells in SLE and their potential contribution to disease remains unclear. Recently, blood CXCR5 CD4 T cells, a heterogeneous pool consisting of functionally distinct Th1-, Th2-, and Th17-like subsets, have been proposed to be the circulating counterpart of Tfh (cTfh) cells. We now ask if changes in cTfh markers or subset composition within blood CXCR5 cells are found in SLE patients, and the extent to which such alterations are associated with B cell and disease activity. Methods: Blood samples from 49 clinically well-characterized SLE patients, 28 Behc ̧et’s disease (BD) patients, and 16 healthy controls were included. Expression of Tfh surface markers (CXCR5; ICOS, inducible T-cell costimulator; PD-1, programmed cell death protein-1), composition of blood CXCR5 subsets, and frequency of plasmablasts were enumerated by flow cytometry. The phenotype of blood CXCR5 subsets was correlated with disease activity, clinical history, and plasmablast expansion. Results: SLE patients had significant expansion of CXCR5 ICOS PD-1 CD4 T cells compared to controls (p 0.001). PD-1, but not ICOS or CXCR5, expression was markedly elevated in CD4 T cells of SLE patients compared to BD patients and healthy controls (p 0.001). PD-1 MFI in CXCR5 cells correlated with SLE disease activity index (SLEDAI; Spearman r 0.43, p 0.03). PD-1 MFI also correlated with expansion of plasmablasts (Spearman r 0.34, p 0.02). In SLE patients with high anti-dsDNA antibody titers, PD-1 expression in CXCR5cells was also significantly elevated compared to patients with no detectable titers (p 0.004). Enhanced PD-1 expression was neither a function of disease duration nor past activity; rather, it reflected current disease activity. Compared to BD patients, SLE patients also had an increase in the CXCR5 Th2 (p 0.05) and a decrease in the Th17 (p 0.001) subsets. Concurrently, PD-1 expression in SLE patients was significantly higher in CXCR5 Th2 cells compared to Th17 cells (p 0.01). The expansion of the CXCR5 Th2 subset was also positively associated with SLEDAI scores. Conclusion: Our results demonstrate that dysregulation of cTfh cells is strongly correlated with disease activity in SLE, supporting a potential causal relationship. The altered composition of blood CXCR5 cells also appeared to be a fundamental cellular defect in SLE, with our results revealing a novel dimension of Tfh dysregulation that may be central to disease pathogenesis.