RESUMO
Monocytes play a key role in pathophysiology of antiphospholipid syndrome (APS), nevertheless it is unclear if microRNA expression is associated with particular APS features. Identify whether miR-19b-3p and miR-20a-5p expression in monocytes are associated with hallmarks of the APS. Fifty-seven APS patients and 18 healthy controls were studied. Expression of miR-19b-3p and miR-20a-5p was measured in monocytes by RT-qPCR. Both miR-19b-3p (AUC = 0.835, 95% CI 0.733-0.938; P < 0.001) and miR-20a-5p (AUC = 0.857, 0.757-0.957; P < 0.001) discriminated APS patients from healthy individuals. A cut-off point of 1.98 for miR-19-3p and 2.18 for miR-20a-5p showed that APS patients with low microRNA expression had higher levels of IgM and IgG anticardiolipin antibodies than patients with high microRNA expression. In addition, APS patients with low microRNA expression had higher IgG anti-ß2 glycoprotein I antibody levels than their counterparts with high microRNA expression. Finally, miR-19b-3p and miR-20a-5p expression levels were significantly higher in APS patients using oral anticoagulants. Monocyte expression of miR-19b-3p and miR-20a-5p is low in APS, and patients with the lowest microRNA expression presented the highest levels of antiphospholipid antibodies.
Assuntos
Anticorpos Antifosfolipídeos/sangue , Síndrome Antifosfolipídica/metabolismo , MicroRNAs/metabolismo , Monócitos/metabolismo , Adulto , Síndrome Antifosfolipídica/sangue , Estudos Transversais , Feminino , Humanos , Masculino , Pessoa de Meia-IdadeRESUMO
AIM: The aim of this study was to identify factors predictive of serious infections over time in patients with systemic lupus erythematosus (SLE). METHODS: A multi-ethnic, multi-national Latin American SLE cohort was studied. Serious infection was defined as one that required hospitalization, occurred during a hospitalization or led to death. Potential predictors included were sociodemographic factors, clinical manifestations (per organ involved, lymphopenia and leukopenia, independently) and previous infections at baseline. Disease activity (SLEDAI), damage (SLICC/ACR Damage Index), non-serious infections, glucocorticoids, antimalarials (users and non-users), and immunosuppressive drugs use; the last six variables were examined as time-dependent covariates. Cox regression models were used to evaluate the predictors of serious infections using a backward elimination procedure. Univariable and multivariable analyses were performed. RESULTS: Of the 1243 patients included, 1116 (89.8%) were female. The median (interquartile range) age at diagnosis and follow-up time were 27 (20-37) years and 47.8 (17.9-68.6) months, respectively. The incidence rate of serious infections was 3.8 cases per 100 person-years. Antimalarial use (hazard ratio: 0.69; 95% confidence interval (CI): 0.48-0.99; p = 0.0440) was protective, while doses of prednisone >15 and ≤60 mg/day (hazard ratio: 4.18; 95 %CI: 1.69-10.31; p = 0.0019) and >60 mg/day (hazard ratio: 4.71; 95% CI: 1.35-16.49; p = 0.0153), use of methylprednisolone pulses (hazard ratio: 1.53; 95% CI: 1.10-2.13; p = 0.0124), increase in disease activity (hazard ratio: 1.03; 95% CI: 1.01-1.04; p = 0.0016) and damage accrual (hazard ratio: 1.22; 95% CI: 1.11-1.34; p < 0.0001) were predictive factors of serious infections. CONCLUSIONS: Over time, prednisone doses higher than 15 mg/day, use of methylprednisolone pulses, increase in disease activity and damage accrual were predictive of infections, whereas antimalarial use was protective against them in SLE patients.
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Hospitalização/estatística & dados numéricos , Infecções/epidemiologia , Lúpus Eritematoso Sistêmico/tratamento farmacológico , Adulto , Antimaláricos/administração & dosagem , Estudos de Coortes , Relação Dose-Resposta a Droga , Feminino , Seguimentos , Glucocorticoides/administração & dosagem , Humanos , Imunossupressores/administração & dosagem , Infecções/etiologia , América Latina , Lúpus Eritematoso Sistêmico/fisiopatologia , Masculino , Metilprednisolona/administração & dosagem , Prednisona/administração & dosagem , Fatores de Proteção , Fatores de Risco , Índice de Gravidade de Doença , Adulto JovemRESUMO
Antiphospholipid syndrome (APS) affects young patients in the most productive years of their life, and the consequences of organic or tissue damage involve a decrease in health-related quality of life (HRQoL). While acute disease manifestations of APS are well known, information on the long-term prognosis and damage in affected patients is still very limited. Systemic lupus erythematosus (SLE) patients would be expected to experience long-term complications and even die as a consequence of APS. Organ damage in APS has been evaluated using different methods and definitions, including the SLICC/ACR Damage Index (SDI), which tend to underestimate aPL-related damage. A new damage index in APS has been proposed (DIAPS), and it seems to be more accurate than SDI. Given the implications for morbidity and mortality, it is imperative to assess accurately aPL-related damage and HRQoL in patients with APS.
Assuntos
Síndrome Antifosfolipídica/reabilitação , Qualidade de Vida , Síndrome Antifosfolipídica/complicações , Humanos , Lúpus Eritematoso Sistêmico/reabilitação , Prognóstico , Psicometria , Índice de Gravidade de Doença , Trombose/etiologiaRESUMO
INTRODUCTION: In antiphospholipid syndrome (APS), certain principal manifestations are associated with a worse prognosis and organ damage. OBJECTIVE: The objective of this paper is to describe the development and initial content, criterion and construct validity of a disease-specific cumulative damage index in patients with thrombotic APS (DIAPS). METHODS: Through expert panel agreement, 47 items were considered to reflect damage in APS. This preliminary version of the DIAPS was submitted to four local and international clinical and research experts in APS who ranked each item according to severity. A Delphi exercise resulted in a final 37 item instrument. In the second phase, a cross-sectional study was conducted applying the DIAPS in patients included in a multicenter electronic registry of patients with APS. Quality of life related to health status was evaluated with the EuroQol for construct validation. An α Cronbach and correlation with the EuroQol scale were calculated with SPSS 20.0 (p < 0.05). RESULTS: We evaluated the DIAPS in 156 patients, 77% female, with a mean age at diagnosis 34.7 ± 5.5 years. A total of 69% had primary APS. Common comorbidities included obesity, depression and dyslipidemia. The most frequent manifestations resulting in sequelae were deep venous thrombosis and ischemic stroke. Blindness, retinal occlusive vessel disease, myocardial infarction, cardiac valve requiring replacement, mesenteric thrombosis, and renal insufficiency also occurred. Homogeneity: α Cronbach 0.619. DIAPS items correlated with EuroQol domains with the exception of pulmonary, renal, gastrointestinal, and endocrine systems. CONCLUSION: This study demonstrates content, criterion and construct validity of a new physician-reported instrument to assess the DIAPS. In addition, the DIAPS correlated with the EuroQol.
Assuntos
Síndrome Antifosfolipídica/patologia , Trombose/patologia , Trombose Venosa/patologia , Adulto , Anticorpos Antifosfolipídeos/imunologia , Síndrome Antifosfolipídica/tratamento farmacológico , Síndrome Antifosfolipídica/imunologia , Comorbidade , Estudos Transversais , Progressão da Doença , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Qualidade de Vida , Índice de Gravidade de Doença , Trombose/imunologia , Trombose Venosa/imunologiaRESUMO
Heart valve disease (HVD) is the most common cardiac manifestation in the antiphospholipid syndrome (APS). Valve lesions should be described according to the established definition. HVD is progressive despite anticoagulant/antiplatelet treatments. Around 4-6% of patients with HVD in APS will require valve replacement surgery, which is considered a very high risk procedure in APS. Unfortunately, no recommendations regarding medical treatment of antiphospholipid antibodies-associated HVD can be made at this moment. There are evidence-based data and strong pathophysiologic rationale for considering HVD as a manifestation of APS. Thus, HVD should be included as a criterion of definite APS.
Assuntos
Síndrome Antifosfolipídica/complicações , Doenças das Valvas Cardíacas/etiologia , Doenças das Valvas Cardíacas/cirurgia , Próteses Valvulares Cardíacas , HumanosRESUMO
A significant correlation between autoimmune diseases and premature or accelerated coronary atherosclerosis has been found. The objectives of the study were: (a) to evaluate myocardial perfusion defects in patients with autoimmune diseases by contrast echocardiography and nuclear imaging; and (b) to evaluate the prevalence of alterations in subclinical myocardial perfusion defects in autoimmune diseases. Myocardial perfusion in 37 patients was evaluated by contrast echocardiography at rest and with dobutamine and with nuclear imaging. The agreement between the two diagnostic tests at rest was 0.72 (P < 0.0001) and with dobutamine was 0.65 (P < 0.0001). The prevalence of abnormalities in myocardial perfusion in autoimmune diseases by contrast echocardiography and nuclear imaging was 27% and in patients with primary antiphospholipid syndrome was 30%. We concluded that there is a high level of agreement between contrast ecocardiography and nuclear imaging for assessment of myocardial perfusion defects in patients with autoimmune diseases, and their prevalence is similar to that reported in the literature.
Assuntos
Doenças Autoimunes/complicações , Doença da Artéria Coronariana/diagnóstico , Adolescente , Adulto , Doenças Autoimunes/diagnóstico , Doença da Artéria Coronariana/etiologia , Diagnóstico Diferencial , Ecocardiografia sob Estresse , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Prognóstico , Estudos Prospectivos , Fatores de Risco , Tomografia Computadorizada de Emissão de Fóton ÚnicoRESUMO
The objective of this study was to assess the possible role of vascular endothelial growth factor (VEGF) in the pathogenesis of systemic lupus erythematosus (SLE) and primary antiphospholipid syndrome (PAPS). We studied 28 patients with SLE, 10 patients with PAPS, and 24 healthy controls. VEGF plasma levels were measured by ELISA. Immunolocalization of VEGF was done in renal tissue from SLE patients and cadaveric controls. Our results showed that VEGF plasma levels were increased in SLE patients compared with PAPS and controls. The correlation between clinical manifestations and VEGF levels revealed that SLE patients with renal failure had significantly increased plasma VEGF levels (134.1 + 91.0 pg/ml) compared with SLE patients with normal renal function (42.9 + 19.0 pg/ml), PAPS patients (41.9 + 26.6 pg/ml), and controls (36.2 + 27.0 pg/ml; P < 0.01). Immunostaining showed a strong expression of VEGF in SLE renal tissue samples. Our preliminary results indicate that VEGF is increased in plasma from patients with lupus nephritis and a moderate degree of renal failure and is overexpressed in renal tissue from these patients.
Assuntos
Síndrome Antifosfolipídica/sangue , Fatores de Crescimento Endotelial/sangue , Nefrite Lúpica/sangue , Linfocinas/sangue , Adulto , Síndrome Antifosfolipídica/patologia , Fatores de Crescimento Endotelial/análise , Feminino , Humanos , Rim/química , Rim/patologia , Nefrite Lúpica/patologia , Linfocinas/análise , Masculino , Pessoa de Meia-Idade , Fator A de Crescimento do Endotélio Vascular , Fatores de Crescimento do Endotélio VascularRESUMO
The results of prospective large cohort studies of patients with different clinical subsets of APS have been reported recently. A significant impact of the disease on long-term survival has been documented in these studies. Cumulative irreversible damage secondary to thrombosis results in organ dysfunction and morbidity. To assess prognosis and treatment in APS, it is imperative to quantify damage. We have recently created and validated an Antiphospholipid Damage Index, which is currently undergoing improvements. Having APS, whether primary or secondary, definitely confers a poor prognosis.
Assuntos
Anticorpos Antifosfolipídeos/análise , Síndrome Antifosfolipídica/patologia , Trombose/etiologia , Adulto , Anticorpos Anticardiolipina/análise , Anticorpos Antifosfolipídeos/imunologia , Síndrome Antifosfolipídica/complicações , Síndrome Antifosfolipídica/tratamento farmacológico , Biomarcadores/análise , Feminino , Morte Fetal , Humanos , Lúpus Eritematoso Sistêmico/complicações , Lúpus Eritematoso Sistêmico/patologia , Morbidade , Gravidez , Complicações na Gravidez , Prognóstico , Recidiva , Índice de Gravidade de Doença , Trombose/patologiaRESUMO
This is a report of a woman in the fifth decade of life with primary antiphospholipid syndrome and involvement of a heart valve. Diagnosis was reached with echocardiography and serological studies.
Assuntos
Síndrome Antifosfolipídica/diagnóstico por imagem , Ecocardiografia Tridimensional , Ecocardiografia , Cardiopatia Reumática/diagnóstico por imagem , Feminino , Humanos , Pessoa de Meia-IdadeRESUMO
A growing body of evidence suggests that aPL are not only serological markers of the antiphospholipid syndrome (APS), but may also directly contribute to the development of thrombosis and other manifestations, including the APS vasculopathy. The latter has been documented in leptmeninges, lung, skin, myocardium, peripheral arteries, and kidney. Renal lesions, a common feature of primary antiphospholipid syndrome (PAPS), include occlusion of principal renal arteries or their main branches, TMA, cortical ischemia, and renal vein thrombosis. Within the cardiac manifestations associated with aPL, valvular involvement is the most common. Histologic findings in valve specimens are consistent with a noninflammatory lesion characterized by intravalvular capillary thrombosis, laminar or verrucous superficial thrombosis, vascular proliferation, fibrosis, and calcification. Even though there is general consensus that endothelial damage triggers the chain of events that results in valve thickening, fusion, rigidity, and ultimately functional abnormalities, we believe that more experimental work remains to be done on the initial valve insult in APS.
Assuntos
Anticorpos Antifosfolipídeos/fisiologia , Síndrome Antifosfolipídica/etiologia , Doenças das Valvas Cardíacas/etiologia , Nefropatias/etiologia , Rim/patologia , Anticorpos Antifosfolipídeos/sangue , Síndrome Antifosfolipídica/patologia , Biomarcadores/sangue , Doenças das Valvas Cardíacas/patologia , Humanos , Nefropatias/patologia , Transplante de Rim/imunologia , Proteína C/antagonistas & inibidores , Trombose/etiologiaRESUMO
APS is found in 20% to 35% of patients with SLE. PAPS and secondary APS have similar features and aPL specificities. The clinical course of the secondary syndrome is independent of the activity and severity of lupus, but the presence of APS worsens the prognosis of patients with lupus. Some features of SLE may result from thrombosis in patients with APS; thus, these patients require anticoagulation rather than corticosteroids. Novel preliminary classification criteria for APS were formulated during a postconference workshop held in Sapporo, Japan, following the Eight International Symposium on Antiphospholipid Antibodies. Treatment of APS remains empirical because of limited controlled prospective data. There is strong evidence that patients with aPL-associated thrombosis are subject to recurrences and require prophylactic therapy. APS is a treatable cause of recurrent fetal loss in women with SLE. The treatment of choice is anticoagulation with heparin, either standard unfractionated heparin or LMWH. One of the main reasons for the improving outcomes in APS pregnancies is closer obstetric surveillance.
Assuntos
Síndrome Antifosfolipídica/etiologia , Lúpus Eritematoso Sistêmico/complicações , Síndrome Antifosfolipídica/diagnóstico , Síndrome Antifosfolipídica/terapia , Diagnóstico Diferencial , Feminino , Morte Fetal , Humanos , Masculino , Prognóstico , Trombose/etiologiaRESUMO
BACKGROUND: A third to half of the patients with primary antiphospholipid syndrome have valve disease. METHODS AND RESULTS: The echocardiographic characteristics of primary antiphospholipid syndrome were analyzed, and the utility of treatment with anticoagulants and/or antiplatelet agents (acetylsalicylic acid) is examined with the use of transesophageal echocardiography in the evaluation of valvular lesions after 1 year of therapy. Twenty-nine patients, 22 women and 7 men with average age of 35.4 years, were studied. Transesophageal echocardiography was performed on all patients before beginning anticoagulant and/or antiplatelet treatment. Valve lesions were found in 22 (75.9%) patients. Of these, other cardiac abnormalities were found in 3 cases, myocardial infarction in 2, and atrial septal defect in 1. In 7 (24.1%) cases, no valvular abnormality was detected, although in 1 of these, alterations in left ventricular segmental wall movement secondary to myocardial infarction were found. One year after initiation of anticoagulant and/or antiplatelet therapy, it was possible to perform transesophageal echocardiograms on 13 patients. No modification of valve lesions was found in 6 (46.2%) cases; new lesions had appeared in the remaining 7 (53.8%) as well as left ventricular apical akinesis in 1 case. CONCLUSIONS: These results indicate that the predominant heart lesion in primary antiphospholipid syndrome is valvular; anticoagulant and/or antiplatelet treatment does not diminish the noninfective valve lesions, and on occasion this entity may be associated with myocardial infarction despite angiographically normal coronary arteries.
Assuntos
Síndrome Antifosfolipídica/diagnóstico por imagem , Ecocardiografia Transesofagiana , Adolescente , Adulto , Idoso , Anticoagulantes/uso terapêutico , Síndrome Antifosfolipídica/complicações , Síndrome Antifosfolipídica/tratamento farmacológico , Diagnóstico Diferencial , Quimioterapia Combinada , Feminino , Seguimentos , Doenças das Valvas Cardíacas/diagnóstico por imagem , Doenças das Valvas Cardíacas/etiologia , Humanos , Masculino , Pessoa de Meia-Idade , Inibidores da Agregação Plaquetária/uso terapêutico , Estudos RetrospectivosRESUMO
The antiphospholipid syndrome, initially described in systemic lupus erythematosus (SLE), occurs in 20-35% of patients with this condition. Its clinical manifestations may precede, be concurrent with, or follow clinical features of SLE. There are no major differences between the primary antiphospholipid syndrome and the secondary form that associates with SLE. Several studies suggest that the presence of an antiphospholipid syndrome in patients with SLE conveys a worse prognosis. To prevent recurrence of thrombotic events (particularly arterial events), oral anticoagulation with an international normalized ratio (INR) close to 3 is recommended. Treatment of recurrent fetal loss is with aspirin, or with aspirin plus heparin. Controlled studies are underway to determine optimal treatment in patients with cerebral ischaemia as well as the optimal treatment in women with recurrent pregnancy loss.
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Aborto Espontâneo/imunologia , Síndrome Antifosfolipídica/complicações , Síndrome Antifosfolipídica/imunologia , Lúpus Eritematoso Sistêmico/complicações , Lúpus Eritematoso Sistêmico/imunologia , Feminino , Humanos , GravidezRESUMO
Antineutrophil cytoplasmic autoantibodies (ANCA) were sought in 43 sera from 39 Mexican patients with typical Takayasu's arteritis (TA), (5 with active and 34 with inactive disease), and in a comparative group comprising 50 sera. Results were negative in all cases. This suggests that ANCA are not a serologic feature in TA per se, even during its active stage. ANCA positivity in TA, when present, may be a non-related phenomenon and probably identifies a subset of patients with atypical forms of TA or a polyangiitis overlap syndrome.
Assuntos
Anticorpos Anticitoplasma de Neutrófilos/análise , Arterite de Takayasu/imunologia , Adulto , Estudos Transversais , Feminino , Humanos , Masculino , México , Prevalência , Arterite de Takayasu/sangue , Arterite de Takayasu/patologiaRESUMO
BACKGROUND: Most systemic lupus erythematosus (SLE) patients with two or more clinical manifestations of the antiphospholipid syndrome (APS) and negative antiphospholipid antibodies (aPL) have antibodies to beta 2-glycoprotein-I (a beta 2 GP-I). Herein we describe a similar set of circumstances, but in patients without evidence of SLE. PATIENTS AND METHODS: We studied 6 patients with recurrent venous and/or arterial thromboses without aPL as detected by routine assays nor clinical or serological evidence of other autoimmune disease. Immunoglobin (Ig) G and IgM antibodies to bovine and human phospholipid-free beta 2 GP-I were studied by Western blot test and by enzyme-linked immunosorbent assay (ELISA) utilizing radiated and nonirradiated plates. We also tested antibodies to cardiolipin, phosphatidylserine, and phosphatidylethanolamine by ELISA. As controls, 54 normal sera were studied. RESULTS: All 6 patients had recurrent arterial and/or venous thromboses. Three also had thrombocytopenia, 1 had livedo reticularis, and 2 had valvular heart disease. None of the patients had aPL, but all had serum IgG reactivity against human and bovine beta 2 GP-I (P < 0.001 versus controls for both). Titers of anti-bovine beta 2 GP-I were higher when studied in irradiated plates but were also higher than normal in nonirradiated plates (P < 0.001). These antibodies did not recognize human or bovine beta 2 GP-I bound to cardiolipin in solid phase. We confirmed by Western blot that these autoantibodies recognize human beta 2 GP-I. We found no IgM a beta 2 GP-I. CONCLUSIONS: We describe a primary condition akin to the antiphospholipid syndrome with negative aPL, but with serum IgG antibodies to human and bovine beta 2 GP-I. These antibodies recognize beta 2 GP-I epitopes that are not accessible when beta 2 GP-I is bound to cardiolipin.
Assuntos
Autoanticorpos/sangue , Glicoproteínas/imunologia , Trombose/imunologia , Adulto , Animais , Western Blotting , Cardiolipinas/imunologia , Bovinos , Ensaio de Imunoadsorção Enzimática , Epitopos , Fator V , Feminino , Genótipo , Glicoproteínas/isolamento & purificação , Humanos , Imunoglobulina G/sangue , Imunoglobulina M/sangue , Masculino , Pessoa de Meia-Idade , Mutação , Fosfatidiletanolaminas/imunologia , Fosfatidilserinas/imunologia , Proteína C , Síndrome , beta 2-Glicoproteína IRESUMO
Pulmonary hypertension may occur in the antiphospholipid syndrome as a result of recurrent pulmonary embolism or microthrombosis of pulmonary vessels. We describe 3 cases of primary antiphospholipid syndrome (APS) and cor pulmonale that fulfilled the criteria for chronic major vessel thromboembolic pulmonary hypertension. Pulmonary thromboendarterectomy was performed in all 3 patients and it was successful in 2. One patient died in the immediate postoperative period from hemorrhagic pulmonary edema. Chronic thromboembolic pulmonary hypertension should be added to the list of pulmonary vascular complications of primary APS. Despite its risk, pulmonary thromboendarterectomy represents a treatment option for this otherwise lethal condition.
Assuntos
Síndrome Antifosfolipídica/complicações , Endarterectomia , Hipertensão Pulmonar/etiologia , Embolia Pulmonar/etiologia , Adulto , Doença Crônica , Evolução Fatal , Feminino , Seguimentos , Humanos , Hipertensão Pulmonar/diagnóstico , Hipertensão Pulmonar/cirurgia , Pulmão/diagnóstico por imagem , Masculino , Artéria Pulmonar/patologia , Embolia Pulmonar/diagnóstico , Embolia Pulmonar/cirurgia , CintilografiaRESUMO
PURPOSE: To evaluate the ocular involvement in patients with the primary antiphospholipid syndrome. METHODS: The authors performed a cross-sectional ophthalmologic study of 17 patients with the primary antiphospholipid syndrome. Retinal fluorangiography was performed in 13 patients. RESULTS: Visual symptoms were described by ten patients. Visual acuity was markedly decreased in five eyes. Conjunctival telangiectases and microaneurysms, in addition to single instances of bilateral episcleritis and limbal keratitis, were the anterior segment findings. Fundus abnormalities were present in 15 patients. Venous tortuosity was the most common finding but there were instances of optic disc edema, vitreous hemorrhages, cotton-wool spots, vitreous bands, serous detachment of the macula, and retinal capillary abnormalities. Fluorangiography showed vaso-occlusive retinopathy in six eyes (5 patients, 29%). Choriocapillary vessel occlusion was observed in two eyes (1 patient) and binocular reticular degeneration of pigmentary epithelium was present in another case. CONCLUSION: The eye is frequently involved in the primary antiphospholipid syndrome, and serious ocular damage may occur. Detailed ophthalmologic evaluation is warranted in these patients.