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1.
Lupus ; 31(9): 1067-1077, 2022 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-35612283

RESUMO

Background: Thrombotic risk in antiphospholipid syndrome (APS) is conferred by the association of antiphospholipid (aPL) antibodies (first hit) with additional pro-coagulant stimulus (second hit), such as inflammation. Among inflammatory responses, the production of large amounts of interferon (IFN)-I by plasmacytoid dendritic cells (pDCs) is at the basis of the pathophysiology of systemic autoimmune disorders, which raises the hypothesis that this mechanism could also be associated with vascular manifestations of APS. Purpose: Here, we determined the association of pDCs and IFN-I production with thrombotic APS. Research design: Patients with thrombotic primary (t-PAPS) and secondary APS (t-SAPS), asymptomatic aPL carriers and individuals without thrombosis (controls) were included. Data collection and analysis: Circulating pDCs and IFN-α intracellular expression (in the presence or not of oligodeoxynucleotides (CP) stimulus) were quantified by flow cytometry. The expression of five IFN-I inducing genes: ISG15, OASL, Ly6E, MX1, and OAS1 in mononuclear cells was determined by qPCR. Between-group differences were evaluated using chi-square or Kruskal-Wallis tests. Results: A total of 50 patients with t-PAPS, 50 patients with t-SAPS, 20 aPL carriers, and 50 individuals without thrombosis (controls) were included. Intracellular expression of IFN-α was increased after CPG stimulation in both t-SAPS (1.56%; IQR 1.07-2.02) and t-PAPS (0.96%; IQR 0.55-1.24), when compared to aPL carriers (0.71%; IQR 0.42-0.93) and controls (0.48%; IQR 0.24-0.78; p < .0001). ISG15, OASL, Ly6E, MX1, and OAS1 mRNA expressions were higher in t-SAPS (but not in t-PAPS) than in aPL carriers and controls. The expression of proteins and mRNA related to IFN-I response was similar between the triple aPL-positive profile and other aPL profiles. Conclusion: Our results indicate an association of IFN-I response and t-APS. Since IFN-I expression was not increased in aPL carriers or associated with a higher-risk aPL profile, this mechanism does not appear to be related to the presence of aPL alone. IFN-I response could possibly constitute a complementary mechanism for triggering clinical manifestations in APS.


Assuntos
Síndrome Antifosfolipídica , Lúpus Eritematoso Sistêmico , Trombose , Anticorpos Antifosfolipídeos , Síndrome Antifosfolipídica/complicações , Antivirais , Células Dendríticas/metabolismo , Humanos , Interferons , Lúpus Eritematoso Sistêmico/complicações , RNA Mensageiro/genética , Trombose/complicações
2.
Lupus ; 30(5): 707-714, 2021 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-33509064

RESUMO

PURPOSE: Primary antiphospholipid syndrome (PAPS) is a chronic autoimmune disorder clinically characterized by thromboembolic events or obstetric complications. Prolonged anticoagulation therapy with vitamin K antagonists (VKA) is the treatment of choice for PAPS patients with thrombosis. However, the efficacy of VKA therapy depends on laboratory monitoring, dose adjustment, adequate lifestyle and adherence to treatment. Difficulties with VKA therapy can affect patients' self-perceived health related quality of life (HRQOL). This study aims to evaluate PAPS patients' HRQOL, therapy adherence and knowledge of treatment. METHODS: A general Medical Outcome Study Short Form-36 (SF-36) and the Duke Anticoagulation Satisfaction Scale (DASS) were used to access APS-patients self-perceived HRQOL. Treatment adherence was measured by the Treatment Measure Adhesion (TMA) - oral anticoagulant version instrument, and knowledge of VKA treatment was measured using the MedTake test. RESULTS: 66 PAPS patients using VKA were assessed. 63% of them were female; the mean age was 41.9 years old, approximately 60% had unprovoked venous thrombosis and one third of the patients had recurrent thrombotic events. The most impacted domain of DASS was "psychological impacts" and the factors associated to anticoagulation related poor HRQOL were: female sex, presence of arterial thrombosis and INR lability. Using the SF-36 instrument, PAPS-patients self-perceived HRQOL was poorer than that of the general Brazilian population and was associated with female sex and presence of cardiovascular risk factors. CONCLUSION: Despite the high adherence to treatment and knowledge of VKA therapy, self-perceived HRQOL is poor in patients with PAPS and is mainly affected by VKA therapy. Searching for better treatment options is warranted.


Assuntos
Síndrome Antifosfolipídica/tratamento farmacológico , Síndrome Antifosfolipídica/psicologia , Qualidade de Vida/psicologia , Autoimagem , Vitamina K/antagonistas & inibidores , Administração Oral , Adulto , Anticoagulantes/uso terapêutico , Síndrome Antifosfolipídica/complicações , Brasil/epidemiologia , Feminino , Fatores de Risco de Doenças Cardíacas , Humanos , Masculino , Pessoa de Meia-Idade , Inquéritos e Questionários/normas , Tromboembolia/epidemiologia , Tromboembolia/etiologia , Trombose/etiologia , Trombose/prevenção & controle , Cooperação e Adesão ao Tratamento/psicologia
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