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1.
Reumatismo ; 71(2): 92-98, 2019 Jul 09.
Artigo em Inglês | MEDLINE | ID: mdl-31309781

RESUMO

A 62-year-old man with a history of systemic sclerosis was admitted with diffuse alveolar hemorrhage and acute kidney injury without clinical data suggestive of glomerulonephritis. Laboratory tests showed anemia, leukocytosis with neutrophilia, thrombocytopenia, elevated serum creatinine and metabolic acidosis. Antinuclear antibodies were positive at a titer of 1/640 (speckled, 1/160; nucleolar, 1/320) while rheumatoid factor, anti Scl-70, anti-centromere, anti-neutrophil cytoplasmic antibody and anti-glomerular basement membrane antibodies were negative and serum complement levels were within normal range. During the following days, the patient developed multiple organ failure and, eventually, died. Lupus anticoagulant was revealed positive after the patient's death, suggesting a catastrophic antiphospholipid syndrome. Clinical data and autopsy were consistent with this diagnosis.


Assuntos
Síndrome Antifosfolipídica/etiologia , Escleroderma Sistêmico/complicações , Doença Catastrófica , Humanos , Masculino , Pessoa de Meia-Idade
2.
Lupus ; 28(9): 1158-1166, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31299879

RESUMO

INTRODUCTION: Although extensively characterized in the outpatient setting, systemic lupus erythematosus (SLE) in the hospitalization wards is still scarcely portrayed, particularly in the perspective of its evolution over the years. METHODS: Retrospective analysis of SLE patients hospitalized in the Department of Autoimmune Diseases of a university hospital during a 20-year period (1995-2015), describing hospitalization characteristics, causes and predictors of outcome. RESULTS: A total of 814 hospitalizations concerning 339 patients were analysed. The main causes of admission were flare (40.2%), infection (19.2%), diagnostic procedures (18.8%) and thrombotic events (5.4%). Therapy with cyclophosphamide (odds ratio (OR) 1.908, p = 0.047) was associated with admission due to infection, while antimalarials displayed a protective effect (OR 0.649, p = 0.024). Nearly 3.9% of patients required admission to an intensive care unit, with associated antiphospholipid syndrome (OR 7.385, p = 0.04) standing as a predicting factor for this outcome. Readmission at 30 days occurred in 5.8% of patients, with thrombocytopenia (OR 6.007, p = 0.002) and renal involvement (OR 3.362, p = 0.032) featuring as predicting factors. Eight patients died, with antiphospholipid syndrome (OR 26.814, p = 0.02) and thrombocytopenia (OR 31.523, p = 0.01) being associated with mortality. There was no significant variation in patients' demographics or admission causes across the 20-year period, except for a decrease in admissions due to thrombotic and musculoskeletal causes. Recently, an increase in the use of mycophenolate mofetil and lower doses of glucocorticoids were noted. CONCLUSION: While demographics of SLE hospitalizations have not markedly changed over the past 20 years, changes in therapy patterns were observed. Thrombocytopenia, antiphospholipid syndrome and renal involvement featured as predictors of poor outcome.


Assuntos
Síndrome Antifosfolipídica/epidemiologia , Hospitalização/estatística & dados numéricos , Lúpus Eritematoso Sistêmico/terapia , Trombocitopenia/epidemiologia , Adulto , Síndrome Antifosfolipídica/etiologia , Ciclofosfamida/administração & dosagem , Feminino , Humanos , Imunossupressores/administração & dosagem , Lúpus Eritematoso Sistêmico/mortalidade , Lúpus Eritematoso Sistêmico/fisiopatologia , Masculino , Pessoa de Meia-Idade , Readmissão do Paciente/estatística & dados numéricos , Estudos Retrospectivos , Espanha , Trombocitopenia/etiologia
4.
Biochem Biophys Res Commun ; 512(1): 72-78, 2019 04 23.
Artigo em Inglês | MEDLINE | ID: mdl-30871774

RESUMO

Accelerated atherosclerosis often occurs in patients with antiphospholipid syndrome (APS), and auto-antibodies to ß2 glycoprotein I (anti-ß2GPI) are confirmed as pathogenic antibodies to APS. Our previous studies have demonstrated that the conversion of mouse peritoneal macrophages into foam cells could be enhanced by co-existence of ß2GPI and anti-ß2GPI IgG, but this phenomenon has not been explored in vivo. Here, we present a mouse model to observe the effect of anti-ß2GPI IgG in the development of atherosclerosis. Male ApoE-deficient mice were intraperitoneally injected with anti-ß2GPI IgG (100 µg/mouse) and homologous control IgG (100 µg/mouse) every week for 16 weeks. Plasma lipid composition, magnetic resonance imaging (MRI) and histological staining were used to evaluate vascular inflammation, lumen stenosis and plaque stability. The results showed that the levels of total cholesterol, triglycerol and low-density lipoprotein-cholesterol in plasma were not changed in all mice fed with high-fat diet, but the level of high-density lipoprotein-cholesterol was lower and the atherosclerosis index was significantly increased in HD + anti-ß2GPI group than in other high-fat diet groups. In addition, compared with NR IgG-treated mice, anti-ß2GPI IgG-treated mice showed more lipid deposition in the carotid artery, markedly narrowed arteriolar lumen as well as higher MMP-9 expression, more macrophages and fewer collagen fibers in the aortic arch root. Furthermore, the aortic mRNA levels of TNF-α, IL-1ß, and MCP-1 were significantly increased in anti-ß2GPI IgG-treated mice. Together, these data indicate that anti-ß2GPI IgG increases vascular inflammation, aggravates atherosclerosis and promotes the formation of vulnerable plaque in ApoE-deficient mice.


Assuntos
Anticorpos Antifosfolipídeos/administração & dosagem , Apolipoproteínas E/deficiência , Aterosclerose/etiologia , beta 2-Glicoproteína I/antagonistas & inibidores , Animais , Síndrome Antifosfolipídica/etiologia , Aterosclerose/patologia , Autoimunidade , Dieta Hiperlipídica/efeitos adversos , Modelos Animais de Doenças , Imunoglobulina G/administração & dosagem , Macrófagos/patologia , Masculino , Camundongos , Camundongos Knockout para ApoE , Placa Aterosclerótica/etiologia , Placa Aterosclerótica/patologia
5.
Hamostaseologie ; 39(2): 188-194, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-30419590

RESUMO

The antiphospholipid syndrome (APS) has occupied haemostaseologists, rheumatologists and obstetricians since its initial description 35 years ago. Its name has been coined because of the antibodies against phospholipids which were the common property of affected patients. In particular, the pathogenesis of APS has been intensively studied after the early discovery that it was possible to induce the clinical manifestations in animals by transfer of antiphospholipid antibodies (aPL). In recent years, it has become clear that aPL are not only structurally heterogeneous but also have different pathogenic properties. This review will focus on the relevance of antigenic specificity of aPL in terms of pathogenesis, diagnosis, and perhaps treatment of APS.


Assuntos
Anticorpos Antifosfolipídeos/imunologia , Síndrome Antifosfolipídica/diagnóstico , Síndrome Antifosfolipídica/terapia , Animais , Síndrome Antifosfolipídica/etiologia , Síndrome Antifosfolipídica/imunologia , Humanos
6.
Asian Pac J Allergy Immunol ; 37(3): 171-178, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-29981567

RESUMO

OBJECTIVES: To describe the characteristics of patients with antiphospholipid syndrome (APS) in an Asian clinical practice setting. METHODS: We conducted a single-center, retrospective study of APS patients attending the rheumatology or hematology clinics, between January 2012 and December 2016. RESULTS: There were 450 patients suspected of having APS referred to our clinics. Seventy-four (16.4%) were diagnosed of APS, 51% of which were definite. Fifty-two (70%) patients were classified as primary APS, 50% of which were definite APS. The most common clinical manifestation was stroke (33%), followed by deep vein thrombosis of the lower extremities (30%) and pulmonary embolism (19%). Hypertension and the presence of at least one established cardiovascular risk factor were independently associated with stroke. Seven (9%) patients had multiorgan thrombosis as their first presentation of APS, 71% of which ultimately suffered from permanent organ damage or died of severe thrombosis, despite not fulfilling the criteria for 'definite' catastrophic APS (CAPS). Late fetal loss was the most prevalent obstetric complication. The majority of patients (79%) tested positive for lupus anticoagulant (LAC), while only 32% tested positive for anti-cardiolipin antibodies. Triple positive profile was documented in 14% of the cohort. Overall, recurrent thrombosis and bleeding complications were recorded in 9% and 28%, respectively. CONCLUSION: APS patients in central Thailand demonstrated high prevalence of stroke, late fetal loss, LAC positivity, and multiorgan thrombosis at first presentation, leading to poor outcomes.


Assuntos
Síndrome Antifosfolipídica/epidemiologia , Síndrome Antifosfolipídica/etiologia , Grupo com Ancestrais do Continente Asiático , Adulto , Síndrome Antifosfolipídica/complicações , Síndrome Antifosfolipídica/diagnóstico , Biomarcadores , Suscetibilidade a Doenças/imunologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Fenótipo , Estudos Retrospectivos , Trombose/diagnóstico , Trombose/etiologia , Trombose/terapia , Resultado do Tratamento , Adulto Jovem
7.
Front Immunol ; 9: 2413, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30405613

RESUMO

APS is an autoimmune disease in which antiphospholipid antibodies (aPL) cause vascular thrombosis and pregnancy morbidity. In patients with APS, aPL exert pathogenic actions by binding serum beta-2-glycoprotein I (ß2GPI) via its N-terminal domain I (DI). We previously showed that bacterially-expressed recombinant DI inhibits biological actions of IgG derived from serum of patients with APS (APS-IgG). DI is too small (7 kDa) to be a viable therapeutic agent. Addition of polyethylene glycol (PEGylation) to small molecules enhances the serum half-life, reduces proteolytic targeting and can decrease immunogenicity. It is a common method of tailoring pharmacokinetic parameters and has been used in the production of many therapies in the clinic. However, PEGylation of molecules may reduce their biological activity, and the size of the PEG group can alter the balance between activity and half-life extension. Here we achieve production of site-specific PEGylation of recombinant DI (PEG-DI) and describe the activities in vitro and in vivo of three variants with different size PEG groups. All variants were able to inhibit APS-IgG from: binding to whole ß2GPI in ELISA, altering the clotting properties of human plasma and promoting thrombosis and tissue factor expression in mice. These findings provide an important step on the path to developing DI into a first-in-class therapeutic in APS.


Assuntos
Síndrome Antifosfolipídica/etiologia , Síndrome Antifosfolipídica/metabolismo , Coagulação Sanguínea , Imunoglobulina G/imunologia , Imunoglobulina G/metabolismo , Domínios e Motivos de Interação entre Proteínas , beta 2-Glicoproteína I/metabolismo , Adulto , Animais , Anticorpos Antifosfolipídeos/sangue , Anticorpos Antifosfolipídeos/imunologia , Síndrome Antifosfolipídica/sangue , Síndrome Antifosfolipídica/diagnóstico , Modelos Animais de Doenças , Ensaio de Imunoadsorção Enzimática , Feminino , Humanos , Masculino , Camundongos , Pessoa de Meia-Idade , Ligação Proteica , Domínios Proteicos , Trombose/sangue , Trombose/etiologia , Trombose/metabolismo , beta 2-Glicoproteína I/química
8.
BMJ Case Rep ; 20182018 Nov 12.
Artigo em Inglês | MEDLINE | ID: mdl-30420561

RESUMO

A 23-year-old woman with history of systemic lupus erythematous presented with dizziness and headache and was admitted for the stroke workup. During her stay, she had sudden painless loss of vision in her right eye consistent with central retinal artery occlusion (CRAO). Ocular massage and paracentesis were attempted without success to resume the flow. She was started on oral high-dose steroids (1 mg/kg) for lupus flare and therapeutic anticoagulation for antiphospholipid syndrome (positive for anticardiolipin and beta-2 microglobulin antibodies). On day 4, she started having painful bluish discoloration of her left index finger and right fifth toe, and on day 5 she had acute onset of left blurry vision with findings consistent with CRAO. She fulfilled the criteria of catastrophic antiphospholipid syndrome and was started on intravenous pulse steroids, plasmapheresis and higher international normalised ratio goal of 3-3.5 with improvement in her left eye vision from 20/200 to 20/20 on near card test by the end of treatment.


Assuntos
Síndrome Antifosfolipídica/etiologia , Lúpus Eritematoso Sistêmico/complicações , Oclusão da Artéria Retiniana/etiologia , Corticosteroides/uso terapêutico , Adulto , Anticoagulantes/uso terapêutico , Síndrome Antifosfolipídica/diagnóstico , Síndrome Antifosfolipídica/terapia , Diagnóstico Diferencial , Feminino , Humanos , Lúpus Eritematoso Sistêmico/tratamento farmacológico , Plasmaferese , Oclusão da Artéria Retiniana/diagnóstico , Oclusão da Artéria Retiniana/terapia , Transtornos da Visão , Adulto Jovem
9.
Expert Rev Clin Immunol ; 14(10): 803-816, 2018 10.
Artigo em Inglês | MEDLINE | ID: mdl-30173578

RESUMO

INTRODUCTION: Systemic lupus erythematosus (SLE) is a chronic autoimmune disorder with systemic manifestations and multiorgan involvement. Although primarily diagnosed, and managed in the outpatient setting, it can occasionally present with life-threatening complications that require rapid assessment and urgent aggressive therapy. Areas covered: In our review, we explore three organ systems that are often affected in SLE, but have the potential to present as medical emergencies; these are the kidney, the central nervous system, and the hematologic system. We take a case-based approach to each clinical scenario, with information given sequentially in order to reflect "real-life" situations where management decisions need to be made with limited information. We review the acute management, pathophysiology, diagnostic approach, and treatment along with a review of the literature, for lupus nephritis presenting as rapidly progressive glomerulonephritis, acute lupus transverse myelitis, and refractory antiphospholipid syndrome. Expert commentary: At the conclusion of each section, we provide an expert commentary regarding each issue, relating to diagnosis, early management, and current evidence behind treatment recommendations.


Assuntos
Síndrome Antifosfolipídica , Lúpus Eritematoso Sistêmico/complicações , Nefrite Lúpica , Vasculite Associada ao Lúpus do Sistema Nervoso Central , Adulto , Síndrome Antifosfolipídica/diagnóstico , Síndrome Antifosfolipídica/etiologia , Síndrome Antifosfolipídica/terapia , Emergências , Feminino , Humanos , Nefrite Lúpica/diagnóstico , Nefrite Lúpica/terapia , Vasculite Associada ao Lúpus do Sistema Nervoso Central/diagnóstico , Vasculite Associada ao Lúpus do Sistema Nervoso Central/terapia
10.
Adv Respir Med ; 86(3)2018.
Artigo em Inglês | MEDLINE | ID: mdl-29960279

RESUMO

Pulmonary embolism is the most common pulmonary manifestation of primary antiphospholipid syndrome (PAPS). However, PAPS may manifest in the respiratory system also due to non-thrombotic processes. In the following paper we present a case of PAPS-related diffuse alveolar hemorrhage (DAH). Because of sparse literature and a lack of randomized controlled trials, there are currently no recommendations regarding the optimal choice of steroid-sparing agent in treating PAPS-related DAH. In our patient, treatment with cyclophosphamide or mycophenolate mofetil along with low dose prednisone was ineffective, partially because of infectious complications, whereas addition of monthly intravenous immunoglobulin to mycophenolate mofetil and prednisone, appears to control the disease.


Assuntos
Síndrome Antifosfolipídica/complicações , Hemorragia/etiologia , Embolia Pulmonar/complicações , Idoso , Síndrome Antifosfolipídica/etiologia , Humanos , Masculino
11.
Ann Rheum Dis ; 77(11): 1549-1557, 2018 11.
Artigo em Inglês | MEDLINE | ID: mdl-30045853

RESUMO

Systemic lupus erythematosus (SLE), a complex and heterogeneous autoimmune disease, represents a significant challenge for both diagnosis and treatment. Patients with SLE in Latin America face special problems that should be considered when therapeutic guidelines are developed. The objective of the study is to develop clinical practice guidelines for Latin American patients with lupus. Two independent teams (rheumatologists with experience in lupus management and methodologists) had an initial meeting in Panama City, Panama, in April 2016. They selected a list of questions for the clinical problems most commonly seen in Latin American patients with SLE. These were addressed with the best available evidence and summarised in a standardised format following the Grading of Recommendations Assessment, Development and Evaluation approach. All preliminary findings were discussed in a second face-to-face meeting in Washington, DC, in November 2016. As a result, nine organ/system sections are presented with the main findings; an 'overarching' treatment approach was added. Special emphasis was made on regional implementation issues. Best pharmacologic options were examined for musculoskeletal, mucocutaneous, kidney, cardiac, pulmonary, neuropsychiatric, haematological manifestations and the antiphospholipid syndrome. The roles of main therapeutic options (ie, glucocorticoids, antimalarials, immunosuppressant agents, therapeutic plasma exchange, belimumab, rituximab, abatacept, low-dose aspirin and anticoagulants) were summarised in each section. In all cases, benefits and harms, certainty of the evidence, values and preferences, feasibility, acceptability and equity issues were considered to produce a recommendation with special focus on ethnic and socioeconomic aspects. Guidelines for Latin American patients with lupus have been developed and could be used in similar settings.


Assuntos
Síndrome Antifosfolipídica/tratamento farmacológico , Doenças Hematológicas/tratamento farmacológico , Nefropatias/tratamento farmacológico , Lúpus Eritematoso Sistêmico/tratamento farmacológico , Síndrome Antifosfolipídica/etiologia , Cardiopatias/tratamento farmacológico , Cardiopatias/etiologia , Doenças Hematológicas/etiologia , Humanos , Nefropatias/etiologia , América Latina , Pneumopatias/tratamento farmacológico , Pneumopatias/etiologia , Lúpus Eritematoso Sistêmico/complicações , Nefrite Lúpica/tratamento farmacológico , Nefrite Lúpica/etiologia , Transtornos Mentais/tratamento farmacológico , Transtornos Mentais/etiologia , Doenças Musculoesqueléticas/tratamento farmacológico , Doenças Musculoesqueléticas/etiologia , Dermatopatias/tratamento farmacológico , Dermatopatias/etiologia , Padrão de Cuidado
12.
Vnitr Lek ; 64(2): 136-145, 2018.
Artigo em Tcheco | MEDLINE | ID: mdl-29595273

RESUMO

The clinical picture of systemic lupus and antiphospholipid syndrome is remarkably varied and disease manifestations are commonly very heterogeneous. Relatively often both diseases are associated with severe, acute and life threatening manifestations, which places demands on the knowledge of differential diagnostics and experience of the physicians. This article deals with the serious and mostly acute impairment of cardiovascular, respiratory, renal, gastrointestinal, hematopoietic or nervous systems, briefly discusses the acute pregnancy complication and summarizes the basic therapeutic option. It emphasizes the role of both, sometimes inseparable, diseases in differential diagnosis of acute symptoms in internal medicine.Key words: clinical symptoms - diagnostics - live threatening manifestations - lupus erythematosus - systemic antiphospholipid syndrome - therapy.


Assuntos
Síndrome Antifosfolipídica , Lúpus Eritematoso Sistêmico , Síndrome Antifosfolipídica/etiologia , Diagnóstico Diferencial , Feminino , Humanos , Medicina Interna , Lúpus Eritematoso Sistêmico/complicações , Lúpus Eritematoso Sistêmico/diagnóstico , Gravidez , Complicações na Gravidez/diagnóstico
13.
Exp Mol Pathol ; 104(2): 151-154, 2018 04.
Artigo em Inglês | MEDLINE | ID: mdl-29551574

RESUMO

Amyloidosis is a disorder characterized by the deposition of insoluble abnormal proteins in the extracellular space. It may occur as a localized lesion or as a systemic disease involving multiple organs and systems. Localized conjunctival amyloidosis is rare and is less frequently associated with systemic involvement. Although amyloidosis itself is a benign lesion involvement of multiple organs and systems is associated with poor prognosis. Diagnosis of amyloidosis is made on biopsy specimens with Congo red staining for the appearance of apple-green birefringence under polarized light microscopy. Liquid chromatography tandem-mass spectrometry (LC-MS/MS) is much more sensitive in diagnosing amyloidosis and can determine the type of amyloid deposit. Here we reported a case of conjunctival amyloidosis in a 52 year-old male patient who was presented with left lower eyelid swelling to our medical center. He has a complicated past medical history of anti-phospholipid antibody syndrome, Buerger's disease (thromboangitis obliterans), and small cell lymphoma (SLL) of the right orbit/eyelid. The patient received radiation to the right orbit to treat SLL with therapy completed one and a half years prior to presentation. Physical examination revealed a firm, raised yellowish colored lesion in the left lower conjunctiva. The conjunctival lesion was biopsied, and tissue sections were examined with Congo red stains and LC-MS/MS analysis. The biopsy showed amyloid deposits without evidence of malignancy, and the type of proteins in the deposit was immunoglobulin light chain (AL) of kappa type. A complete work up was taken for possible systemic involvement of amyloidosis and results were all negative. To our knowledge, this is the first case of localized conjunctival amyloidosis with a history of contralateral orbit/eyelid SLL.


Assuntos
Amiloidose/patologia , Doenças da Túnica Conjuntiva/patologia , Linfoma/patologia , Neoplasias Orbitárias/patologia , Síndrome Antifosfolipídica/etiologia , Biópsia , Humanos , Linfoma/radioterapia , Linfoma não Hodgkin/radioterapia , Masculino , Pessoa de Meia-Idade , Órbita/patologia , Neoplasias Orbitárias/radioterapia , Tromboangiite Obliterante/etiologia
14.
Neurocrit Care ; 28(1): 127-132, 2018 02.
Artigo em Inglês | MEDLINE | ID: mdl-28357636

RESUMO

BACKGROUND: Catastrophic antiphospholipid syndrome (CAPS) is a rare, severe variant of antiphospholipid syndrome with a high mortality rate. We report a unique case of CAPS secondary to Epstein-Barr viral (EBV) infection complicated by pulmonary and intracerebral hemorrhage. A review of the CAPS literature relevant to intensive care practice is used to outline a rational approach to diagnosis and management. METHODS: All data are from a single patient admitted to the Neurosciences Critical Care Unit in Addenbrooke's Hospital, Cambridge, in March 2016. Medline, Web of Science, PubMed, and the Cochrane Library were searched through September 2016 without restrictions for cases of CAPS, management of CAPS in the intensive care unit, and hemorrhage complicating CAPS. The patient gave express written consent to access and publish these data. RESULTS: This is only the second reported case of probable CAPS secondary to EBV infection. Furthermore, pulmonary and intracerebral hemorrhage is rare manifestations of this multisystem prothrombotic state which provided unique challenges to the management. CONCLUSIONS: While rare, CAPS should be considered in any patient presenting with rapidly progressive multiorgan failure, evidence of thrombotic microangiopathy, and antiphospholipid antibodies. A high index of suspicion is required as early, aggressive, multimodal treatment with anticoagulation, and immunosuppression improves outcomes.


Assuntos
Síndrome Antifosfolipídica/etiologia , Hemorragia Cerebral/etiologia , Infecções por Vírus Epstein-Barr/complicações , Adulto , Humanos , Masculino , Adulto Jovem
15.
Best Pract Res Clin Rheumatol ; 31(3): 397-414, 2017 06.
Artigo em Inglês | MEDLINE | ID: mdl-29224680

RESUMO

Systemic lupus erythematosus (SLE) is a chronic inflammatory autoimmune disease with a high prevalence in females of childbearing age. Pregnancy in SLE nowadays has favorable outcomes for the majority of women. However, flares of disease activity, preeclampsia, fetal loss, and preterm birth are well-known risks in such pregnancies. Anti-SS-A(Ro)/SS-B(La) antibodies put fetuses at risk for congenital heart block and neonatal lupus. Several risk factors for adverse pregnancy outcomes have been identified. Women with antiphospholipid antibodies or antiphospholipid syndrome and lupus nephritis represent a group with high risk for obstetric complications. Factors such as appropriate preconception counseling and medication adjustment, strict disease control prior to pregnancy, and intensive surveillance during and after pregnancy are essential to improve pregnancy outcome. The aim of this review article is to update on the medical care of pregnancy in these women to ensure the best maternal and fetal prognosis.


Assuntos
Síndrome Antifosfolipídica/etiologia , Lúpus Eritematoso Sistêmico/etiologia , Complicações na Gravidez/tratamento farmacológico , Síndrome Antifosfolipídica/patologia , Feminino , Humanos , Lúpus Eritematoso Sistêmico/complicações , Lúpus Eritematoso Sistêmico/patologia , Gravidez , Resultado da Gravidez , Prognóstico , Fatores de Risco
17.
J Thromb Thrombolysis ; 44(4): 565-570, 2017 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-29027631

RESUMO

Antiphospholipid syndrome (APS) is an autoimmune disease that is characterized by arterial and/or venous thrombosis and/or recurrent pregnancy losses. Obstetric APS (OAPS) is considered as a distinct entity from vascular APS (VAPS). In the absence of any additional disease, APS is designated as primary (PAPS), while the term secondary APS (SAPS) is used when other diseases are associated. Catastrophic APS (CAPS) is characterized by the rapid development of multiple thrombosis in various vital organs. The presence of antiphospholipid antibodies (aPL Abs) is considered as a laboratory criterion for APS diagnosis. aPL Abs cause an increase in systemic and decidual TNF-alpha levels in experimental model of APS (eAPS), while paradoxically, administration of TNF-alpha blockers has been associated with de novo synthesis of aPL Abs in patients with various autoimmune diseases. While eAPS provides evidence for the fact that application of TNF-alpha blockers has beneficial effects, lack of randomized prospective studies is the main obstacle for consideration of TNF-alpha blockers administration as a therapeutic option not for all, but at least for selected cases of APS patients despite compelling evidence for detrimental roles of TNF-alpha for both VASP and OAPS. This article represents a review of previously published reports on detrimental roles of TNF-alpha in APS, reports on the application of anti-TNF-alpha agents in eAPS and articles that reported de novo synthesis of aPL Abs induced by biopharmaceuticals against TNF-alpha.


Assuntos
Anticorpos Antifosfolipídeos/sangue , Síndrome Antifosfolipídica/diagnóstico , Fator de Necrose Tumoral alfa/efeitos adversos , Fator de Necrose Tumoral alfa/antagonistas & inibidores , Animais , Anticorpos Antifosfolipídeos/biossíntese , Anticorpos Antifosfolipídeos/efeitos dos fármacos , Síndrome Antifosfolipídica/tratamento farmacológico , Síndrome Antifosfolipídica/etiologia , Humanos
18.
J Thromb Haemost ; 15(12): 2367-2376, 2017 12.
Artigo em Inglês | MEDLINE | ID: mdl-29024318

RESUMO

Essentials Antiphospholipid antibodies (aPL) are heterogeneous and induce different cellular responses. We analyzed signaling events induced by different monoclonal and patient aPL in monocytes. Two major signaling pathways involving either NADPH-oxidase or LRP8 were identified. Our data suggest that these two pathways mediate the majority of aPL effects on monocytes. SUMMARY: Background Antiphospholipid antibodies (aPLs) contribute to the pathogenesis of the antiphospholipid syndrome (APS) by induction of an inflammatory and procoagulant state in different cell types, and several signaling pathways have been described. Objectives To investigate whether signaling depends on the epitope specificity of aPLs. Methods Cellular effects of three human monoclonal aPLs with distinctly different epitope specificities were analyzed in vitro. Expression of tumor necrosis factor-α mRNA by mouse and human monocytes was the major readout. Analysis included cells from genetically modified mice, and the use of specific inhibitors in human monocytes. Data were validated with IgG isolated from 20 APS patients. Results Cofactor-independent anticardiolipin aPLs activated monocytes by induction of endosomal NADPH oxidase. Activation could be blocked by hydroxychloroquine (HCQ). Anti-ß2 -glycoprotein I aPL activated monocytes by interacting with LDL receptor-related protein 8 (LRP8). This could be blocked by rapamycin. Analysis of 20 APS patients' IgG showed that all IgG fractions activated the same two pathways as the monoclonal aPL, depending on their epitope patterns as determined by ELISA. Monocyte activation by APS IgG could be blocked completely by HCQ and/or rapamycin, suggesting that in most, if not all, APS patients there is no other relevant signaling pathway. Conclusions aPLs activate two major proinflammatory signal transduction pathways, depending on their epitope specificity. HCQ and rapamycin, either alone or in combination, completely suppress signaling by APS IgG. These observations may provide a rationale for specific treatment of APS patients according to their aPL profile.


Assuntos
Anticorpos Antifosfolipídeos/imunologia , Síndrome Antifosfolipídica/imunologia , Adulto , Animais , Anticorpos Anticardiolipina/imunologia , Anticorpos Monoclonais/imunologia , Especificidade de Anticorpos , Síndrome Antifosfolipídica/etiologia , Epitopos/imunologia , Feminino , Humanos , Imunoglobulina G/imunologia , Técnicas In Vitro , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Pessoa de Meia-Idade , Monócitos/imunologia , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Transdução de Sinais/imunologia , Fator de Necrose Tumoral alfa/genética
19.
Lupus ; 26(13): 1351-1367, 2017 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-28728509

RESUMO

Cardiovascular events (CVEs) are prevalent in patients with systemic lupus erythematosus (SLE), and it is the young women who are disproportionately at risk. The risk factors for accelerated cardiovascular disease remain unclear, with multiple studies producing conflicting results. In this paper, we aim to address both traditional and SLE-specific risk factors postulated to drive the accelerated vascular disease in this cohort. We also discuss the more recent hypothesis that adverse pregnancy outcomes in the form of maternal-placental syndrome and resultant preterm delivery could potentially contribute to the CVEs seen in young women with SLE who have fewer traditional cardiovascular risk factors. The pathophysiology of how placental-mediated vascular insufficiency and hypoxia (with the secretion of placenta-like growth factor (PlGF) and soluble fms-tyrosine-like kinase-1 (sFlt-1), soluble endoglin (sEng) and other placental factors) work synergistically to damage the vascular endothelium is discussed. Adverse pregnancy outcomes ultimately are a small contributing factor to the complex pathophysiological process of cardiovascular disease in patients with SLE. Future collaborative studies between cardiologists, obstetricians, obstetric physicians and rheumatologists may pave the way for a better understanding of a likely multifactorial aetiological process.


Assuntos
Doenças Cardiovasculares/etiologia , Lúpus Eritematoso Sistêmico/complicações , Complicações na Gravidez , Adulto , Síndrome Antifosfolipídica/etiologia , Feminino , Humanos , Hidroxicloroquina/uso terapêutico , Lúpus Eritematoso Sistêmico/tratamento farmacológico , Masculino , Síndrome Metabólica/complicações , Gravidez , Fatores Sexuais , Fumar/efeitos adversos
20.
Intern Med ; 56(10): 1207-1212, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-28502938

RESUMO

A 37-year-old woman with extranodal marginal-zone lymphoma was admitted with a fever, hemiplegia, and severe dyspnea after chemotherapy. Catastrophic antiphospholipid antibody syndrome (CAPS) was suspected based on the histopathological confirmation of small-pulmonary vessel occlusion, evidence of the involvement of three organs, and elevated lupus anticoagulant assay results in a short time span. The patient responded to the initial treatment. One month later, the CAPS and lymphoma relapsed, and the patient underwent autologous hematopoietic stem cell transplantation. Complete remission of the lymphoma has been successfully maintained, and the condition of the patient has remained stable for two years with no further evidence of thrombosis.


Assuntos
Síndrome Antifosfolipídica/etiologia , Síndrome Antifosfolipídica/terapia , Transplante de Células-Tronco Hematopoéticas , Linfoma de Zona Marginal Tipo Células B/complicações , Linfoma de Zona Marginal Tipo Células B/terapia , Adulto , Feminino , Humanos , Indução de Remissão , Transplante Autólogo , Resultado do Tratamento
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