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1.
Arthritis Res Ther ; 21(1): 212, 2019 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-31615552

RESUMO

BACKGROUND: Systemic sclerosis (SSc) is a potentially fatal autoimmune disease that leads to extensive fibrosis of the skin and internal organs. Invariant natural killer T (iNKT) cells are potent immunoregulatory T lymphocytes being able to orchestrate dysregulated immune responses. The purpose of this study was to evaluate numbers and function of iNKT cells in patients with SSc and to analyze their correlation with disease parameters. METHODS: Human iNKT cells from 88 patients with SSc and 33 healthy controls were analyzed by flow cytometry. Their proliferative capacity and cytokine production were investigated following activation with CD1d ligand α-galactosylceramide (α-GalCer). RESULTS: We observed an absolute and relative decrease of iNKT cells in patients with SSc compared with healthy controls. Interestingly, the subtype of SSc, disease severity, or treatment with immunosuppressive drugs did not affect iNKT cell numbers. However, T helper (Th) cell immune polarization was biased towards a Th17 immunophenotype in SSc patients. Moreover, iNKT cells from patients with SSc showed a significantly decreased expansion capacity upon stimulation with α-GalCer. CONCLUSION: iNKT cells are deficient and functionally impaired in patients with SSc. Therefore, adoptive transfer strategies using culture-expanded iNKT cells could be a novel approach to treat SSc patients.

2.
Ann Rheum Dis ; 78(11): 1576-1582, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31391176

RESUMO

OBJECTIVES: To investigate the influence of vasodilator drugs on the occurrence of features depending on myocardial ischaemia/fibrosis (ventricular arrhythmias, Q waves, cardiac blocks, pacemaker implantation, left ventricular ejection fraction (LVEF) <55%, and/or congestive heart failure and sudden cardiac death) in systemic sclerosis (SSc). METHODS: 601 patients with SSc were enrolled from 1 December 2012 to 30 November 2015 and had a second visit 0.5-4 years apart. 153 received no vasodilators; 448 received vasodilator therapy (ie, calcium channel blockers and/or ACE inhibitors or angiotensin II receptor blockers or combinations of them), 89 of them being also treated with either endothelin receptor antagonists or PDE5 inhibitors or prostanoids. Associations between the occurrence of myocardial disease manifestations and any demographic, disease and therapeutic aspect were investigated by Cox regression analysis. A Cox frailty survival model with centre of enrolment as random effect was performed. RESULTS: During 914 follow-up patient-years, 12 ventricular arrhythmias, 5 Q waves, 40 cardiac blocks, 6 pacemaker implantations and 19 reduced LVEF and/or congestive heart failure (CHF) occurred. In multivariate Cox regression analysis, vasodilator therapy was associated with a lower incidence of ventricular arrhythmias (p=0.03); low-dose acetylsalicylic acid (ASA) with a lower incidence of cardiac blocks and/or Q waves and/or pacemaker implantation (p=0.02); active disease with a higher incidence of LVEF <55% and/or CHF and cardiac blocks and/or Q waves and/or pacemaker implantation (p=0.05). CONCLUSIONS: The present study might suggest a preventative effect on the occurrence of distinct myocardial manifestations by vasodilator therapy and low-dose ASA.

5.
Rheumatol Int ; 30(5): 709-12, 2010 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-20012622

RESUMO

Rituximab has only been approved in combination with methotrexate for the treatment of rheumatoid arthritis. As some patients have intolerance to methotrexate, alternative co-therapies are needed. This method involved retrospective analysis of ten patients treated with a combination of rituximab and leflunomide. Primary outcome measures were the DAS28 response at month 6 and the time to relapse. The median initial DAS 28 of 5.7 (3.2-7.2) was reduced to 3.5 (1.9-6.1) at month 6. 70% of the patients achieved a good or moderate response, whereas 30% showed no response. Two patients had to stop leflunomide due to adverse effects. Two patients had to reduce the leflunomide dose to 10 mg/day. 5/8 patients experienced a relapse after a median of 10 (6-30) months and were successfully re-treated with rituximab. This small case series suggests that leflunomide might offer an alternative DMARD combination option for the treatment of RA with rituximab.


Assuntos
Anticorpos Monoclonais/uso terapêutico , Antirreumáticos/uso terapêutico , Artrite Reumatoide/tratamento farmacológico , Isoxazóis/uso terapêutico , Adulto , Idoso , Anticorpos Monoclonais/efeitos adversos , Anticorpos Monoclonais Murinos , Antirreumáticos/efeitos adversos , Artrite Reumatoide/diagnóstico , Quimioterapia Combinada , Feminino , Humanos , Isoxazóis/efeitos adversos , Leflunomida , Masculino , Pessoa de Meia-Idade , Recidiva , Estudos Retrospectivos , Rituximab , Índice de Gravidade de Doença , Fatores de Tempo , Resultado do Tratamento
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