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1.
Clin Rheumatol ; 39(9): 2811-2815, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32720260

RESUMO

In the midst of the COVID-19 pandemic, further understanding of its complications points towards dysregulated immune response as a major component. Systemic lupus erythematosus (SLE) is also a disease of immune dysregulation leading to multisystem compromise. We present a case of new-onset SLE concomitantly with COVID-19 and development of antiphospholipid antibodies. An 18-year-old female that presented with hemodynamic collapse and respiratory failure, progressed to cardiac arrest, and had a pericardial tamponade drained. She then progressed to severe acute respiratory distress syndrome, severe ventricular dysfunction, and worsening renal function with proteinuria and hematuria. Further studies showed bilateral pleural effusions, positive antinuclear and antidouble-stranded DNA antibodies, lupus anticoagulant, and anticardiolipin B. C3 and C4 levels were low. SARS-Cov-2 PCR was positive after 2 negative tests. She also developed multiple deep venous thrombosis, in the setting of positive antiphospholipid antibodies and lupus anticoagulant. In terms of pathophysiology, COVID-19 is believed to cause a dysregulated cytokine response which could potentially be exacerbated by the shift in Th1 to Th2 response seen in SLE. Also, it is well documented that viral infections are an environmental factor that contributes to the development of autoimmunity; however, COVID-19 is a new entity, and it is not known if it could trigger autoimmune conditions. Additionally, it is possible that SARS-CoV-2, as it happens with other viruses, might lead to the formation of antiphospholipid antibodies, potentially contributing to the increased rates of thrombosis seen in COVID-19.


Assuntos
Síndrome Antifosfolipídica/imunologia , Infecções por Coronavirus/imunologia , Lúpus Eritematoso Sistêmico/imunologia , Pneumonia Viral/imunologia , Adolescente , Anemia/etiologia , Anticorpos Anticardiolipina/imunologia , Anticorpos Antinucleares/imunologia , Anticorpos Monoclonais Humanizados/uso terapêutico , Síndrome Antifosfolipídica/complicações , Síndrome Antifosfolipídica/diagnóstico , Síndrome Antifosfolipídica/terapia , Anuria/etiologia , Betacoronavirus , Tamponamento Cardíaco/diagnóstico por imagem , Tamponamento Cardíaco/etiologia , Tamponamento Cardíaco/terapia , Complemento C3/imunologia , Complemento C4/imunologia , Infecções por Coronavirus/complicações , Infecções por Coronavirus/diagnóstico , Infecções por Coronavirus/terapia , DNA/imunologia , Ecocardiografia , Evolução Fatal , Feminino , Parada Cardíaca/etiologia , Hematúria/etiologia , Humanos , Inibidor de Coagulação do Lúpus/imunologia , Lúpus Eritematoso Sistêmico/sangue , Lúpus Eritematoso Sistêmico/complicações , Lúpus Eritematoso Sistêmico/diagnóstico , Pandemias , Posicionamento do Paciente , Pericardiocentese , Pneumonia Viral/complicações , Pneumonia Viral/diagnóstico , Pneumonia Viral/terapia , Decúbito Ventral , Proteinúria/etiologia , Diálise Renal , Insuficiência Renal/etiologia , Insuficiência Renal/terapia , Respiração Artificial , /terapia , Insuficiência Respiratória/etiologia , Insuficiência Respiratória/terapia , Trombocitopenia/etiologia , Trombose Venosa/etiologia , Disfunção Ventricular Esquerda/diagnóstico por imagem
3.
J Crit Care ; 59: 32-34, 2020 10.
Artigo em Inglês | MEDLINE | ID: mdl-32512349

RESUMO

The novel coronavirus strain known as SARS-CoV-2 has rapidly spread around the world creating distinct challenges to the healthcare workforce. Coagulopathy contributing to significant morbidity in critically ill patients with SARS-CoV-2 has now been well documented. We discuss two cases selected from patients requiring critical care in April 2020 in New York City with a unique clinical course. Both cases reveal significant thrombotic events noted on imaging during their hospital course. Obtaining serial inflammatory markers in conjunction with anti-phospholipid antibody testing revealed clinically significant Antiphospholipid syndrome (APS). This case series reviews the details preceding APS observed in SARS-CoV-2 and aims to report findings that could potentially further our understanding of the disease.


Assuntos
Anticorpos Anticardiolipina/imunologia , Síndrome Antifosfolipídica/sangue , Infecções por Coronavirus/sangue , Pneumonia Viral/sangue , Trombose/sangue , Adulto , Anticorpos Monoclonais Humanizados/uso terapêutico , Anticoagulantes/uso terapêutico , Síndrome Antifosfolipídica/complicações , Síndrome Antifosfolipídica/imunologia , Antivirais/uso terapêutico , Arteriopatias Oclusivas/etiologia , Betacoronavirus , Infarto Cerebral/etiologia , Angiografia por Tomografia Computadorizada , Infecções por Coronavirus/complicações , Infecções por Coronavirus/tratamento farmacológico , Infecções por Coronavirus/imunologia , Estado Terminal , Feminino , Heparina/uso terapêutico , Humanos , Hidroxicloroquina/uso terapêutico , Proteína Antagonista do Receptor de Interleucina 1/uso terapêutico , Masculino , Pessoa de Meia-Idade , Cidade de Nova Iorque , Pandemias , Pneumonia Viral/complicações , Pneumonia Viral/tratamento farmacológico , Pneumonia Viral/imunologia , Infarto do Baço/etiologia , Trombose/tratamento farmacológico , Trombose/etiologia , Artérias da Tíbia
4.
Int J Mol Med ; 46(3): 903-912, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32588061

RESUMO

The severe acute respiratory syndrome coronavirus 2 (SARS­CoV­2) is a novel ß coronavirus that is the etiological agent of the pandemic coronavirus disease 2019 (COVID­19) that at the time of writing (June 16, 2020) has infected almost 6 million people with some 450,000 deaths. These numbers are still rising daily. Most (some 80%) cases of COVID­19 infection are asymptomatic, a substantial number of cases (15%) require hospitalization and an additional fraction of patients (5%) need recovery in intensive care units. Mortality for COVID­19 infection appears to occur globally between 0.1 and 0.5% of infected patients although the frequency of lethality is significantly augmented in the elderly and in patients with other comorbidities. The development of acute respiratory distress syndrome and episodes of thromboembolism that may lead to disseminated intravascular coagulation (DIC) represent the primary causes of lethality during COVID­19 infection. Increasing evidence suggests that thrombotic diathesis is due to multiple derangements of the coagulation system including marked elevation of D­dimer that correlate negatively with survival. We propose here that the thromboembolic events and eventually the development of DIC provoked by SARS­CoV­2 infection may represent a secondary anti­phospholipid antibody syndrome (APS). We will apply both Baconian inductivism and Cartesian deductivism to prove that secondary APS is likely responsible for coagulopathy during the course of COVID­19 infection. Diagnostic and therapeutic implications of this are also discussed.


Assuntos
Síndrome Antifosfolipídica/patologia , Infecções por Coronavirus/patologia , Coagulação Intravascular Disseminada/patologia , Pneumonia Viral/patologia , Tromboembolia/patologia , Trombose/patologia , Síndrome Antifosfolipídica/imunologia , Antivirais/uso terapêutico , Betacoronavirus , Coagulação Sanguínea/fisiologia , Infecções por Coronavirus/tratamento farmacológico , Infecções por Coronavirus/imunologia , Coagulação Intravascular Disseminada/imunologia , Produtos de Degradação da Fibrina e do Fibrinogênio/metabolismo , Humanos , Pandemias , Fosfolipídeos/imunologia , Pneumonia Viral/tratamento farmacológico , Pneumonia Viral/imunologia , Tromboembolia/imunologia
5.
Adv Rheumatol ; 60(1): 32, 2020 06 09.
Artigo em Inglês | MEDLINE | ID: mdl-32517786

RESUMO

Hydroxychloroquine and chloroquine, also known as antimalarial drugs, are widely used in the treatment of rheumatic diseases and have recently become the focus of attention because of the ongoing COVID-19 pandemic. Rheumatologists have been using antimalarials to manage patients with chronic immune-mediated inflammatory rheumatic diseases for decades. It is an appropriate time to review their immunomodulatory and anti-inflammatory mechanisms impact on disease activity and survival of systemic lupus erythematosus patient, including antiplatelet effect, metabolic and lipid benefits. We also discuss possible adverse effects, adding a practical and comprehensive approach to monitoring rheumatic patients during treatment with these drugs.


Assuntos
Antimaláricos/farmacologia , Artrite Reumatoide/tratamento farmacológico , Cloroquina/farmacologia , Hidroxicloroquina/farmacologia , Lúpus Eritematoso Sistêmico/tratamento farmacológico , Síndrome Antifosfolipídica/tratamento farmacológico , Síndrome Antifosfolipídica/imunologia , Antirreumáticos/uso terapêutico , Artrite Reumatoide/imunologia , Infecções por Coronavirus/tratamento farmacológico , Erupção por Droga/etiologia , Interações Medicamentosas , Feminino , Glucose/metabolismo , Cardiopatias/induzido quimicamente , Humanos , Lipídeos/sangue , Lúpus Eritematoso Cutâneo/tratamento farmacológico , Lúpus Eritematoso Cutâneo/imunologia , Lúpus Eritematoso Sistêmico/imunologia , Lúpus Eritematoso Sistêmico/mortalidade , Masculino , Pandemias , Agregação Plaquetária/efeitos dos fármacos , Pneumonia Viral/tratamento farmacológico , Gravidez , Insuficiência Renal/prevenção & controle , Doenças Retinianas/induzido quimicamente , Síndrome de Sjogren/tratamento farmacológico , Síndrome de Sjogren/imunologia
8.
Transl Res ; 225: 70-81, 2020 11.
Artigo em Inglês | MEDLINE | ID: mdl-32413497

RESUMO

Antiphospholipid syndrome is one of the more common acquired causes of hypercoagulability. Its major presentations are thrombotic (arterial, venous, or microvascular) and pregnancy morbidity (miscarriages, late intrauterine fetal demise, and severe pre-eclampsia). Classification criteria include 3 different antiphospholipid antibodies: lupus anticoagulant, anticardiolipin, and anti-beta 2 glycoprotein I. Management includes both preventive strategies (low-dose aspirin, hydroxychloroquine) and long-term anticoagulation after thrombosis.


Assuntos
Síndrome Antifosfolipídica/complicações , Anticorpos Antifosfolipídeos/análise , Anticoagulantes/uso terapêutico , Síndrome Antifosfolipídica/tratamento farmacológico , Síndrome Antifosfolipídica/imunologia , Humanos
9.
Int J Mol Sci ; 21(6)2020 Mar 18.
Artigo em Inglês | MEDLINE | ID: mdl-32197340

RESUMO

MicroRNAs (miRNAs) are single-stranded, endogenous RNA molecules that play a significant role in the regulation of gene expression as well as cell development, differentiation, and function. Recent data suggest that these small molecules are responsible for the regulation of immune responses. Therefore, they may act as potent modulators of the immune system and play an important role in the development of several autoimmune diseases. Antiphospholipid syndrome (APS) is an autoimmune systemic disease characterized by venous and/or arterial thromboses and/or recurrent fetal losses in the presence of antiphospholipid antibodies (aPLs). Several lines of evidence suggest that like other autoimmune disorders, miRNAs are deeply involved in the pathogenesis of APS, interacting with the function of innate and adaptive immune responses. In this review, we characterize miRNAs in the light of having a functional role in the immune system and autoimmune responses focusing on APS. In addition, we also discuss miRNAs as potential biomarkers and target molecules in treating APS.


Assuntos
Imunidade Adaptativa , Síndrome Antifosfolipídica/imunologia , Imunidade Inata , MicroRNAs/imunologia , Síndrome Antifosfolipídica/patologia , Biomarcadores , Humanos
10.
Z Rheumatol ; 79(3): 255-266, 2020 Apr.
Artigo em Alemão | MEDLINE | ID: mdl-32185464

RESUMO

Antiphospholipid syndrome (APS) was first identified in patients with systemic lupus erythematosus (SLE) and frequent occurrence of thromboembolic complications and miscarriages accompanied by detection of anticardiolipin antibodies (aCL). When APS was also later found without an underlying SLE, the so-called primary APS was distinguished from its secondary form with SLE. Even more specific than aCL are the lupus anticoagulant (LA) and antibodies against beta­2 glycoprotein I (aB2GP I). In recent years, it has become evident that the risk of (further) thromboembolic and obstetric complications is markedly increased if all three serological criteria of APS (aCL, aB2GP I and LA), the so-called triple positivity, are present (high-risk profile). Immunosuppression is not effective in preventing further thromboembolic complications of APS. Low-dose aspirin (LDA), heparin and vitamin K antagonists are used in primary and secondary prophylaxis. The direct oral anticoagulants have an increased risk of complications compared to these treatments and should not be used in cases of high-risk APS.


Assuntos
Anticorpos Anticardiolipina/imunologia , Síndrome Antifosfolipídica , Lúpus Eritematoso Sistêmico , Anticoagulantes/uso terapêutico , Síndrome Antifosfolipídica/diagnóstico , Síndrome Antifosfolipídica/imunologia , Síndrome Antifosfolipídica/terapia , Feminino , Humanos , Lúpus Eritematoso Sistêmico/complicações , Lúpus Eritematoso Sistêmico/imunologia , Gravidez , beta 2-Glicoproteína I
11.
Arthritis Res Ther ; 22(1): 33, 2020 02 21.
Artigo em Inglês | MEDLINE | ID: mdl-32085759

RESUMO

BACKGROUND: Despite expansion in the 2006 Sydney antiphospholipid syndrome (APS) classification criteria to include IgG/IgM anti-ß2-glycoprotein (aß2GPI) antibodies in addition to IgG/IgM anti-cardiolipin antibodies (aCL) and lupus anticoagulant (LAC), some individuals with clinical features of APS remain seronegative (seronegative APS or SNAPS) and are at risk of recurrent thrombosis and pregnancy morbidities. Our aim was to assess the value of "non-criteria" aPL antibodies to detect these SNAPS patients. METHODS: One hundred ninety-two APS patients, 90 SNAPS patients, 193 autoimmune disease controls, and 120 healthy controls were evaluated. Ten antiphospholipid antibodies (aPLs) were tested using commercial kits, including 5 non-criteria aPLs: anti-phosphatidylserine/prothrombin antibodies (aPS/PT) IgG/IgM, aCL IgA, aß2GPI IgA, and anti-ß2GPI Domain 1 (aß2GPI-D1) IgG. RESULTS: Up to 60.9% of the SNAPS and 93.5% of APS patients were detected by at least one non-criteria aPL. aPS/PT IgG had the highest Youden index in classifying APS and SNAPS from controls. aPS/PT IgG and aß2GPI Domain 1 IgG seem to be the most significant risk factors for thrombotic events and pregnancy morbidity, respectively. aPS/PT IgG/IgM and aß2GPI-D1 IgG were detected in some SNAPS patients, while IgA isotypes of aCL/aß2GPI tended to appear together with other biomarkers. The combined analysis showed enhanced diagnostic performance with the inclusion of non-criteria aPLs. CONCLUSIONS: Recognition of SNAPS patients is critical for clinical management and prevention of potential thrombotic and obstetric adverse events. The non-criteria antiphospholipid antibodies help to identify a considerable portion (60.9%) of these patients who otherwise may remain untreated and at clinical risk.


Assuntos
Anticorpos Antifosfolipídeos/imunologia , Síndrome Antifosfolipídica/diagnóstico , Síndrome Antifosfolipídica/imunologia , Adulto , Anticorpos Antifosfolipídeos/sangue , Síndrome Antifosfolipídica/sangue , Grupo com Ancestrais do Continente Asiático , Estudos de Casos e Controles , Estudos de Coortes , Feminino , Humanos , Masculino , Pessoa de Meia-Idade
12.
Lupus ; 29(3): 256-262, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-31986962

RESUMO

BACKGROUND: Antiphospholipid syndrome (APS) is an acquired thrombophilia that affects young productive individuals, with permanent damage and negative impact on quality of life. Recently, a damage index specific for APS (DIAPS) was developed. There are, however, no data regarding the comparison of its performance and long-term damage in primary antiphospholipid syndrome (PAPS) and APS related to systemic lupus erythematosus (SLE; APS + SLE). The primary purpose of this study was therefore to compare the long-term damage in patients with these conditions. METHODS: This is a retrospective analysis of a single tertiary center cohort followed for approximately 10 years using a standardized prospective electronic chart database. Fifty consecutive PAPS patients age matched with 50 APS+SLE patients were consecutively selected for the study, and DIAPS was calculated once a year during follow-up. Long-term damage and damage kinetics in both groups were compared. RESULTS: PAPS and APS + SLE had comparable age (47.10 ± 12.4 vs. 44.04 ± 10.80 years; p = 0.19) and time of follow-up (9.40 ± 3.60 vs. 10.94 ± 4.50 years; p = 0.06). At diagnosis, PAPS had higher DIAPS than APS + SLE (1.72 ± 1.17 vs. 0.82 ± 0.96; p < 0.001). At the end of the 10-year follow-up, both groups presented comparable mean damage scores (2.04 ± 1.50 vs. 2.24 ± 1.61; p = 0.52). The damage increment throughout the observation period for PAPS was solely 35%, whereas for APS + SLE it was gradual, persistent and reached 139% at the end of follow-up, with a total damage increment for PAPS lower than APS + SLE (0.43 ± 0.30 vs. 1.22 ± 1.24; p < 0.001). Of note, the frequency of individuals who acquired damage was lower in PAPS than in APS + SLE (32% vs. 71%; p < 0.001). PAPS also had a longer delay in diagnosis than APS + SLE (4.00 ± 4.20 vs. 2.54 ± 3.05 years; p = 0.04). This delay was positively correlated with a higher damage score at diagnosis (r = 0.36, p < 0.001) in all groups. CONCLUSION: We identified a distinct pattern of damage in PAPS and APS related to SLE. Damage in PAPS is an early event, while APS+SLE is associated with higher long-term damage, with a striking increment of damage along the follow-up. A diagnosis delay is correlated with higher damage scores. Damage surveillance therefore requires different approaches for these two conditions.


Assuntos
Síndrome Antifosfolipídica/diagnóstico , Autoanticorpos/sangue , Lúpus Eritematoso Sistêmico/diagnóstico , Adulto , Síndrome Antifosfolipídica/complicações , Síndrome Antifosfolipídica/imunologia , Progressão da Doença , Feminino , Humanos , Cinética , Lúpus Eritematoso Sistêmico/complicações , Lúpus Eritematoso Sistêmico/imunologia , Masculino , Pessoa de Meia-Idade , Qualidade de Vida , Estudos Retrospectivos , Índice de Gravidade de Doença
14.
Lupus ; 29(2): 157-164, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31948351

RESUMO

INTRODUCTION: Antiphospholipid syndrome (APS) is associated with greater atherothrombotic risk and endothelial dysfunction, suggesting that endothelial glycocalyx is impaired in this disease. OBJECTIVES: The aim was to investigate the endothelial glycocalyx and the relationship between glycocalyx markers, endothelial dysfunction parameters and atherosclerotic markers in APS. METHODS: A total of 15 primary arterial APS patients and healthy controls were included in the study. Glycocalyx was assessed in both groups by sublingual sidestream dark field imaging and syndecan-1 plasma level. Endothelial function was evaluated by brachial artery flow-mediated dilatation (FMD) and early atherosclerosis by carotid intima media thickness (IMT). Thrombotic profile was also performed by measuring the plasma level of the tissue factor (TF). RESULTS: APS patients had significantly increased syndecan-1 plasma level 38.6 ± 5.0 pg/ml vs. 19.1 ± 3.5 pg/ml; p < 0.01 and a reduced glycocalyx thickness 0.26 ± 0.03 µm vs. 0.75 ± 0.07 µm; p < 0.01 compared with control. FMD was impaired in APS patients compared with control, 5.68% ± 0.42 vs. 8.29 ± 0.30, p < 0.01, respectively. IMT was significantly increased in APS patients compared with control, 0.52 ± 0.13 mm vs. 0.40 ± 0.06 mm, p < 0.01, respectively. Soluble TF, thiobarbituric acid-reactive substances levels were increased in the sera from APS patients compared with control. CONCLUSIONS: This preliminary study supports, for the first time, that in APS patients endothelial glycocalyx is impaired, which could lead to thrombosis, endothelial dysfunction and early atherosclerosis.


Assuntos
Síndrome Antifosfolipídica/fisiopatologia , Aterosclerose/etiologia , Autoanticorpos/imunologia , Endotélio Vascular/fisiopatologia , Glicocálix/patologia , Trombose/etiologia , Adolescente , Adulto , Idoso , Síndrome Antifosfolipídica/sangue , Síndrome Antifosfolipídica/imunologia , Biomarcadores/sangue , Artéria Braquial/diagnóstico por imagem , Artérias Carótidas/diagnóstico por imagem , Espessura Intima-Media Carotídea , Estudos de Casos e Controles , Estudos Transversais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Fatores de Risco , Sindecana-1/sangue , Tromboplastina/análise , Vasodilatação , Adulto Jovem
16.
Ann Rheum Dis ; 79(2): 254-261, 2020 02.
Artigo em Inglês | MEDLINE | ID: mdl-31704719

RESUMO

​OBJECTIVES: A single nucleotide polymorphism in the NCF1 gene (NCF1-339, rs201802880), encoding NADPH oxidase type II subunit NCF1/p47phox, reducing production of reactive oxygen species (ROS) is strongly associated with the development of systemic lupus erythematosus (SLE). This study aimed at characterising NCF1-339 effects on neutrophil extracellular trap (NET) formation, type I interferon activity and antibody profile in patients with SLE. ​METHODS: Neutrophil NET-release pathways (n=31), serum interferon (n=141) and finally antibody profiles (n=305) were investigated in SLE subjects from Lund, genotyped for NCF1-339. Then, 1087 SLE subjects from the rheumatology departments of four Swedish SLE centres, genotyped for NCF1-339, were clinically characterised to validate these findings. ​RESULTS: Compared with patients with normal-ROS NCF1-339 genotypes, neutrophils from patients with SLE with low-ROS NCF1-339 genotypes displayed impaired NET formation (p<0.01) and increased dependence on mitochondrial ROS (p<0.05). Low-ROS patients also had increased frequency of high serum interferon activity (80% vs 21.4%, p<0.05) and positivity for anti-ß2 glycoprotein I (p<0.01) and anticardiolipin antibodies (p<0.05) but were not associated with other antibodies. We confirmed an over-representation of having any antiphospholipid antibody, OR 1.40 (95% CI 1.01 to 1.95), anti-ß2 glycoprotein I, OR 1.82 (95% CI 1.02 to 3.24) and the antiphospholipid syndrome (APS), OR 1.74 (95% CI 1.19 to 2.55) in all four cohorts (n=1087). ​CONCLUSIONS: The NCF1-339 SNP mediated decreased NADPH oxidase function, is associated with high interferon activity and impaired formation of NETs in SLE, allowing dependence on mitochondrial ROS. Unexpectedly, we revealed a striking connection between the ROS deficient NCF1-339 genotypes and the presence of phospholipid antibodies and APS.


Assuntos
Síndrome Antifosfolipídica/genética , Armadilhas Extracelulares/genética , Interferon Tipo I/sangue , Lúpus Eritematoso Sistêmico/genética , NADPH Oxidases/genética , Adulto , Anticorpos Anticardiolipina/sangue , Anticorpos Antifosfolipídeos/sangue , Síndrome Antifosfolipídica/imunologia , Feminino , Genótipo , Humanos , Lúpus Eritematoso Sistêmico/sangue , Lúpus Eritematoso Sistêmico/imunologia , Masculino , NADPH Oxidase 2/genética , Polimorfismo de Nucleotídeo Único , Espécies Reativas de Oxigênio , Suécia
17.
J Thromb Haemost ; 18(2): 463-478, 2020 02.
Artigo em Inglês | MEDLINE | ID: mdl-31749277

RESUMO

BACKGROUND: Classification of the antiphospholipid syndrome (APS) relies predominantly on detecting antiphospholipid antibodies (aPLs). Antibodies against a domain I (DI) epitope of anti-ß2glycoprotein I (ß2GPI) proved to be pathogenic, but are not included in the current classification criteria. OBJECTIVES: Investigate the clinical value of detecting anti-DI IgG in APS. PATIENTS/METHODS: From eight European centers 1005 patients were enrolled. Anti-cardiolipin (CL) and anti-ß2GPI were detected by four commercially available solid phase assays; anti-DI IgG by the QUANTA Flash® ß2GPI domain I assay. RESULTS: Odds ratios (ORs) of anti-DI IgG for thrombosis and pregnancy morbidity proved to be higher than those of the conventional assays. Upon restriction to patients positive for anti-ß2GPI IgG, anti-DI IgG positivity still resulted in significant ORs. When anti-DI IgG was added to the criteria aPLs or used as a substitute for anti-ß2GPI IgG/anti-CL IgG, ORs for clinical symptoms hardly improved. Upon removing anti-DI positive patients, lupus anticoagulant remained significantly correlated with clinical complications. Anti-DI IgG are mainly present in high-risk triple positive patients, showing higher levels. Combined anti-DI and triple positivity confers a higher risk for clinical symptoms compared to only triple positivity. CONCLUSIONS: Detection of anti-DI IgG resulted in higher ORs for clinical manifestations than the current APS classification criteria. Regardless of the platform used to detect anti-ß2GPI/anti-CL, addition of anti-DI IgG measured by QUANTA Flash® did not improve the clinical associations, possibly due to reduced exposure of the pathogenic epitope of DI. Our results demonstrate that anti-DI IgG potentially helps in identifying high-risk patients.


Assuntos
Anticorpos Anticardiolipina/sangue , Síndrome Antifosfolipídica/imunologia , Imunoglobulina G/sangue , Luminescência , Complicações Cardiovasculares na Gravidez/imunologia , beta 2-Glicoproteína I/imunologia , Adulto , Idoso , Anticorpos Anticardiolipina/imunologia , Epitopos/química , Feminino , Humanos , Imunoglobulina G/imunologia , Inibidor de Coagulação do Lúpus/imunologia , Masculino , Pessoa de Meia-Idade , Razão de Chances , Gravidez , Domínios Proteicos , Reprodutibilidade dos Testes , beta 2-Glicoproteína I/química
18.
Blood ; 135(4): 239-251, 2020 01 23.
Artigo em Inglês | MEDLINE | ID: mdl-31812994

RESUMO

The antiphospholipid syndrome (APS) is characterized by thrombosis and/or pregnancy morbidity in the presence of antiphospholipid antibodies, including anti-ß2-glycoprotein-I (anti-ß2GPI), that are considered central to APS pathogenesis. Based on animal studies showing a role of complement in APS-related clinical events, we used the modified Ham (mHam) assay (complement-dependent cell killing) and cell-surface deposition of C5b-9 to test the hypothesis that complement activation is associated with thrombotic events in APS. A positive mHam (and corresponding C5b-9 deposition) were present in 85.7% of catastrophic APS (CAPS), 35.6% of APS (and 68.5% of samples collected within 1 year of thrombosis), and only 6.8% of systemic lupus erythematosus (SLE) sera. A positive mHam assay was associated with triple positivity (for lupus anticoagulant, anticardiolipin, and anti-ß2GPI antibodies) and recurrent thrombosis. Patient-derived anti-ß2GPI antibodies also induced C5b-9 deposition, which was blocked completely by an anti-C5 monoclonal antibody, but not by a factor D inhibitor, indicating that complement activation by anti-ß2GPI antibodies occurs primarily through the classical complement pathway. Finally, patients with CAPS have high rates of rare germline variants in complement regulatory genes (60%), compared with patients with APS (21.8%) or SLE (28.6%) or normal controls (23.3%), and have mutations at a rate similar to that of patients with atypical hemolytic uremic syndrome (51.5%). Taken together, our data suggest that anti-ß2GPI antibodies activate complement and contribute to thrombosis in APS, whereas patients with CAPS have underlying mutations in complement regulatory genes that serve as a "second hit," leading to uncontrolled complement activation and a more severe thrombotic phenotype.


Assuntos
Síndrome Antifosfolipídica/complicações , Ativação do Complemento , Trombose/etiologia , Adulto , Idoso , Anticorpos Antifosfolipídeos/imunologia , Síndrome Antifosfolipídica/genética , Síndrome Antifosfolipídica/imunologia , Feminino , Regulação da Expressão Gênica , Mutação em Linhagem Germinativa , Humanos , Masculino , Pessoa de Meia-Idade , Trombose/genética , Trombose/imunologia , beta 2-Glicoproteína I/imunologia
19.
Rheumatology (Oxford) ; 59(7): 1539-1544, 2020 07 01.
Artigo em Inglês | MEDLINE | ID: mdl-31630203

RESUMO

OBJECTIVES: Non-conventional aPL have been described in patients presenting clinical manifestations of antiphospholipid syndrome but negative for conventional markers. Among them, detection of autoantibodies against prothrombin has been proposed to improve diagnosis and management of these patients. However autoantibodies against prothrombin are heterogeneous and their use in clinical practice still remains unclear. The aim of this study was to evaluate the interest of IgG and IgM autoantibodies directed against the prothrombin only (aPT). METHODS: We retrospectively studied IgM and IgG aPT results, conventional antiphospholipid syndrome markers and clinical data of a large cohort of 441 patients referred for antiphospholipid syndrome exploration with aPT detection over a period of 5 years. RESULTS: We observed a total prevalence of 17% of aPT-positive patients (75/441). A significant association was found between aPT and thrombosis (P = 0.035), with 70% of patients having unexplained thrombosis, aPT representing the sole aPL detected. aPT positivity was significantly more frequent in venous thrombosis than in arterial thrombosis (P = 0.004). Interestingly, we demonstrated for the first time that aPT IgG levels were higher in recurrent thrombosis than in isolated thrombosis (P = 0.013), leading us to propose a predictive level of recurrence for thrombosis. CONCLUSION: Our results show that aPT are associated with thrombosis and demonstrate the interest of assessing both IgG and IgM aPT, in particular in venous thrombosis when conventional markers are negative. Quantification of aPT could predict recurrence of thrombosis and influence subsequent treatment strategy. Prospective clinical studies are now required to confirm these results.


Assuntos
Anticorpos Antifosfolipídeos/imunologia , Síndrome Antifosfolipídica/imunologia , Imunoglobulina G/imunologia , Imunoglobulina M/imunologia , Protrombina/imunologia , Embolia Pulmonar/imunologia , Trombose Venosa/imunologia , Adulto , Anticorpos Anticardiolipina/imunologia , Síndrome Antifosfolipídica/complicações , Artérias , Autoanticorpos/imunologia , Ensaio de Imunoadsorção Enzimática , Feminino , Humanos , Ataque Isquêmico Transitório/etiologia , Ataque Isquêmico Transitório/imunologia , Inibidor de Coagulação do Lúpus/imunologia , Masculino , Pessoa de Meia-Idade , Embolia Pulmonar/etiologia , Recidiva , Estudos Retrospectivos , Acidente Vascular Cerebral/etiologia , Acidente Vascular Cerebral/imunologia , Trombose/etiologia , Trombose/imunologia , Trombose Venosa/etiologia , beta 2-Glicoproteína I/imunologia
20.
Lupus ; 29(2): 105-117, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31829084

RESUMO

Antiphospholipid syndrome is a systemic autoimmune disease associated with obstetric complications along with vascular events affecting multiple organ systems in patients having positive titers of antiphospholipid antibodies. Eight to 20% of infertility cases have an unknown cause, part of which could be due to antiphospholipid syndrome. Although still debatable, many studies have addressed the relation between reproductive failure and antiphospholipid antibodies through the relation between antiphospholipid antibodies and unexplained infertility as well as the effect of antiphospholipid antibodies on the outcome of in vitro fertilization-embryo transfer. Few studies and cases have associated the presence of antiphospholipid antibodies with male infertility, describing morphofunctional penile abnormalities and testicular infarction. There are not enough data to support the routine practice of testing antiphospholipid antibodies in patients with infertility.


Assuntos
Aborto Habitual/imunologia , Anticorpos Antifosfolipídeos/imunologia , Infertilidade Feminina/imunologia , Infertilidade Masculina/imunologia , Aborto Habitual/patologia , Animais , Síndrome Antifosfolipídica/imunologia , Síndrome Antifosfolipídica/patologia , Feminino , Fertilização In Vitro , Humanos , Infertilidade Feminina/patologia , Infertilidade Masculina/patologia , Masculino , Gravidez
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