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1.
Int J Mol Sci ; 21(24)2020 Dec 15.
Artigo em Inglês | MEDLINE | ID: mdl-33333988

RESUMO

As in many autoimmune diseases, the pathogenesis of the antiphospholipid syndrome (APS) is the result of a complex interplay between predisposing genes and triggering environmental factors, leading to a loss of self-tolerance and immune-mediated tissue damage. While the first genetic studies in APS focused primarily on the human leukocytes antigen system (HLA) region, more recent data highlighted the role of other genes in APS susceptibility, including those involved in the immune response and in the hemostatic process. In order to join this intriguing debate, we analyzed the single-nucleotide polymorphisms (SNPs) derived from the whole exome sequencing (WES) of two siblings affected by APS and compared our findings with the available literature. We identified genes encoding proteins involved in the hemostatic process, the immune response, and the phospholipid metabolism (PLA2G6, HSPG2, BCL3, ZFAT, ATP2B2, CRTC3, and ADCY3) of potential interest when debating the pathogenesis of the syndrome. The study of the selected SNPs in a larger cohort of APS patients and the integration of WES results with the network-based approaches will help decipher the genetic risk factors involved in the diverse clinical features of APS.


Assuntos
Síndrome Antifosfolipídica/genética , Síndrome Antifosfolipídica/metabolismo , Predisposição Genética para Doença , Estudo de Associação Genômica Ampla , Alelos , Anticorpos Antifosfolipídeos/genética , Anticorpos Antifosfolipídeos/imunologia , Síndrome Antifosfolipídica/complicações , Síndrome Antifosfolipídica/diagnóstico , Biologia Computacional/métodos , Feminino , Perfilação da Expressão Gênica , Humanos , Masculino , Pessoa de Meia-Idade , Polimorfismo de Nucleotídeo Único , Trombose/etiologia , Sequenciamento Completo do Exoma
2.
Rheumatol Int ; 40(10): 1539-1554, 2020 10.
Artigo em Inglês | MEDLINE | ID: mdl-32666137

RESUMO

The coronavirus disease-2019 (COVID-19) pandemic is likely to pose new challenges to the rheumatology community in the near and distant future. Some of the challenges, like the severity of COVID-19 among patients on immunosuppressive agents, are predictable and are being evaluated with great care and effort across the globe. A few others, such as atypical manifestations of COVID-19 mimicking rheumatic musculoskeletal diseases (RMDs) are being reported. Like in many other viral infections, severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection can potentially lead to an array of rheumatological and autoimmune manifestations by molecular mimicry (cross-reacting epitope between the virus and the host), bystander killing (virus-specific CD8 + T cells migrating to the target tissues and exerting cytotoxicity), epitope spreading, viral persistence (polyclonal activation due to the constant presence of viral antigens driving immune-mediated injury) and formation of neutrophil extracellular traps. In addition, the myriad of antiviral drugs presently being tried in the treatment of COVID-19 can result in several rheumatic musculoskeletal adverse effects. In this review, we have addressed the possible spectrum and mechanisms of various autoimmune and rheumatic musculoskeletal manifestations that can be precipitated by COVID-19 infection, its therapy, and the preventive strategies to contain the infection.


Assuntos
Doenças Autoimunes/fisiopatologia , Infecções por Coronavirus/fisiopatologia , Doenças Musculoesqueléticas/fisiopatologia , Pneumonia Viral/fisiopatologia , Doenças Reumáticas/fisiopatologia , Anticorpos Antinucleares/imunologia , Anticorpos Antifosfolipídeos/imunologia , Antivirais/efeitos adversos , Artralgia/etiologia , Artralgia/imunologia , Artralgia/fisiopatologia , Doenças Autoimunes/etiologia , Doenças Autoimunes/imunologia , Betacoronavirus , Transtornos da Coagulação Sanguínea/etiologia , Transtornos da Coagulação Sanguínea/imunologia , Transtornos da Coagulação Sanguínea/fisiopatologia , Infecções por Coronavirus/complicações , Infecções por Coronavirus/tratamento farmacológico , Infecções por Coronavirus/imunologia , Reações Cruzadas/imunologia , Armadilhas Extracelulares/imunologia , Produtos de Degradação da Fibrina e do Fibrinogênio , Síndrome de Guillain-Barré/etiologia , Síndrome de Guillain-Barré/imunologia , Síndrome de Guillain-Barré/fisiopatologia , Humanos , Inibidor de Coagulação do Lúpus/imunologia , Mimetismo Molecular , Síndrome de Linfonodos Mucocutâneos/etiologia , Síndrome de Linfonodos Mucocutâneos/imunologia , Síndrome de Linfonodos Mucocutâneos/fisiopatologia , Debilidade Muscular/etiologia , Debilidade Muscular/imunologia , Debilidade Muscular/fisiopatologia , Doenças Musculoesqueléticas/etiologia , Doenças Musculoesqueléticas/imunologia , Mialgia/etiologia , Mialgia/imunologia , Mialgia/fisiopatologia , Miocardite/etiologia , Miocardite/imunologia , Miocardite/fisiopatologia , Pandemias , Pneumonia Viral/complicações , Pneumonia Viral/tratamento farmacológico , Pneumonia Viral/imunologia , Doenças Reumáticas/etiologia , Doenças Reumáticas/imunologia
4.
Clin Exp Immunol ; 201(1): 94-104, 2020 07.
Artigo em Inglês | MEDLINE | ID: mdl-32297318

RESUMO

The risk of premature death is high among patients on haemodialysis (HD patients). We previously determined that immunoglobulin (Ig)M antibodies against phosphorylcholine (anti-PC) are negatively associated with increased risk of cardiovascular disease (CVD), atherosclerosis, some autoimmune diseases and mortality among HD patients in this cohort. Here, we also study other subclasses and isotypes of anti-PC in HD patients in relation to mortality, inflammation and gender. The study group is a cohort of 209 prevalent HD patients [median age = 66 years, interquartile range (IQR) = 51-74], vintage time = 29 months (IQR = 15-58; 56% men) with a mean follow-up period of 41 months (IQR = 20-60). Fifty-six per cent were men. We also divided patients into inflamed C-reactive protein (CRP) > 5·6 mg/ml and non-inflamed CRP. Antibody levels were determined by in-house enzyme-linked immunosorbent assay. IgG1 anti-PC below median was significantly associated with increased all-cause mortality (after adjustment for confounders: P = 0·02), while IgG, IgA and IgG2 anti-PC were not associated with this outcome. Among non-inflamed patients, IgM and IgG1 anti-PC were significantly associated with mortality (P = 0·047 and 0·02). IgG1 anti-PC was significantly associated with mortality among men (P = 0·03) and trending among women (P = 0·26). IgM (as previously reported) and IgG1 anti-PC are negatively associated with survival among HD patients and non-inflamed HD patients, but among inflamed patients there were no associations. IgG, IgA or IgG2 anti-PC were not associated with survival in these groups and subgroups. Further studies are needed to determine if raising anti-PC levels, especially IgM and IgG1 anti-PC, through immunization is beneficial.


Assuntos
Anticorpos Antifosfolipídeos/imunologia , Fosforilcolina/imunologia , Diálise Renal , Insuficiência Renal Crônica , Idoso , Anticorpos Antifosfolipídeos/classificação , Proteína C-Reativa/imunologia , Doenças Cardiovasculares/etiologia , Doenças Cardiovasculares/imunologia , Doenças Cardiovasculares/mortalidade , Doenças Cardiovasculares/patologia , Intervalo Livre de Doença , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Insuficiência Renal Crônica/imunologia , Insuficiência Renal Crônica/terapia , Taxa de Sobrevida
5.
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
6.
PLoS One ; 15(1): e0227836, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-31929597

RESUMO

Behçet's disease (BD) is a multifactorial systemic inflammatory disease of unknown aetiology characterised by several clinical manifestations including vascular involvements (i.e., both arterial and venous thrombosis). Antiphospholipid antibodies (aPLs)-including anticardiolipin (aCL), anti-ß2-glycoprotein I (ß2-GPI) antibodies and lupus anticoagulant (LA) are detected in systemic autoimmune diseases which contribute to thrombosis. The aim of this systematic review and meta-analysis was to evaluate the prevalence of aPLs in patients with BD as compared to controls. A protocol was registered in PROSPERO (Registration No. CRD42018088125) and a systematic literature search was conducted through PubMed, Web of Science, Embase, Scopus and ScienceDirect databases. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated using random-effects model. Quality assessment was carried out by using the modified 9-star Newcastle-Ottawa Scale (NOS). Publication bias was evaluated via visualisation of contour- enhanced and trim and fill funnel plots along with Begg's and Egger's tests. We included ten case-control studies (a total of 999 participants from 380 BD patients and 619 controls) based on the inclusion criteria. The prevalence of aCL (OR: 12.10, 95% CI: 5.15-28.41, p<0.00001) and anti-ß2-GPI antibodies (OR: 23.57, 95% CI: 1.31-423.63, p = 0.03) were statistically significant, however, the prevalence of LA was not significant (OR: 13.77, 95% CI: 0.65-293.59, p = 0.09). The results remained statistically significant from different sensitivity analyses which represented the robustness of this meta-analysis. According to the NOS, 50.0% of the studies were considered as of high methodological quality (low risk of bias). No significant publication bias was detected from contour-enhanced and trim and fill funnel plots or Begg's and Egger's tests. This meta-analysis established that there is a significantly high prevalence of aPLs (i.e., aCL and anti-ß2-GPI antibodies) in patients with BD when compared to controls.


Assuntos
Anticorpos Antifosfolipídeos/imunologia , Síndrome de Behçet/imunologia , Anticorpos Anticardiolipina/sangue , Anticorpos Anticardiolipina/imunologia , Anticorpos Antifosfolipídeos/sangue , Síndrome de Behçet/sangue , Síndrome de Behçet/epidemiologia , Humanos , Prevalência , beta 2-Glicoproteína I/imunologia
8.
Autoimmunity ; 53(1): 21-27, 2020 02.
Artigo em Inglês | MEDLINE | ID: mdl-31782311

RESUMO

Background: Systemic lupus erythematosus (SLE) is associated with a constellation of complications affecting multiple organs, including neuropsychiatric manifestations (NPSLE) and ischaemic events, leading to increased long-term morbidity. Antiphospholipid antibodies (aPL) are a major determinant of vascular inflammation and thromboembolic risk. The diagnostic role of anti-phosphatidylserine/prothrombin (aPS/PT) antibodies in this setting is incompletely defined.Aim: To verify whether aPS/PT add to diagnostics and disease stratification in patients with SLE with or without other aPL.Methods: 131 consecutive patients were studied, including 20 patients with SLE and secondary antiphospholipid syndrome (APS). aPS/PT IgG and IgM were assessed through ELISA and patients were stratified based on the presence of other aPL, on their clinical and laboratory features at time of blood sampling and on their clinical history. Synthetic indices of disease activity, chronic damage and cardiovascular risk were calculated at time of venipuncture.Results: Fifty-one (38.9%) patients with SLE had aPS/PT and 15 (11.5%) patients had aPS/PT as the only aPL (aPS/PT-only). aPS/PT-only patients had a significantly higher prevalence of NPSLE than quadruple aPL-negative patients (p = .007). Patients with aPS/PT were more likely to have a history of ischaemia, thrombocytopenia and Libman-Sacks' endocarditis. The presence of aPS/PT also associated with previous accrual of at least one damage item (p = .043), but had limited predictive values for damage progression in the short term.Conclusion: aPS/PT antibodies provide non-redundant information that could contribute to risk assessment and stratification of patients with SLE.


Assuntos
Anticorpos Antifosfolipídeos/imunologia , Doenças Cardiovasculares/diagnóstico , Doenças Cardiovasculares/etiologia , Lúpus Eritematoso Sistêmico/complicações , Lúpus Eritematoso Sistêmico/imunologia , Vasculite Associada ao Lúpus do Sistema Nervoso Central/diagnóstico , Vasculite Associada ao Lúpus do Sistema Nervoso Central/etiologia , Autoimunidade , Diabetes Mellitus Tipo 1/imunologia , Feminino , Humanos , Lúpus Eritematoso Sistêmico/epidemiologia , Masculino , Fenótipo , Prevalência , Protrombina/imunologia
9.
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
10.
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
11.
Mod Rheumatol ; 30(1): 116-124, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-30557100

RESUMO

Objectives: Thrombocytopenia is frequently observed in antiphospholipid antibody (aPL) carriers. Due to the paradoxical risks of thrombosis and hemorrhage, the management of aPL-associated thrombocytopenia (APAT) is often deductive. We aimed to investigate the efficacy and safety of therapeutic approaches for APAT through a systematic review.Methods: Four therapeutic approaches for APAT, including antiplatelet agents, glucocorticoids, splenectomy and thrombopoietin receptor agonists, were selected. Clinical trials evaluating therapeutic outcomes including the remission, complications, mortality and relapse, were searched in MEDLINE, EMBASE and CENTRAL from the inception dates to 28 November 2016. A meta-analysis was performed to calculate risk ratios (RRs) and 95% confidence intervals (CIs) using random-effects models.Results: Out of 1407 papers, eight controlled clinical trials were included. In patients with APAT, the remission rates were higher in patients on glucocorticoids (RR 8.33 [95% CI 3.07-22.6]) or splenectomy (RR 8.37 [95% CI 1.61-43.7]) than in patients without those treatments. There was no significant association between glucocorticoids and thrombosis (RR 1.57 [95% CI, 0.17-14.9]) or between splenectomy and hemorrhage (RR 0.17 [95% CI 0.02-1.28]). The extracted data of mortality and relapse rate were not available for synthesis.Conclusion: Glucocorticoids or splenectomy seemed suitable therapeutic approaches for APAT.


Assuntos
Anticorpos Antifosfolipídeos/imunologia , Glucocorticoides/uso terapêutico , Hemorragia/prevenção & controle , Inibidores da Agregação de Plaquetas/uso terapêutico , Esplenectomia/métodos , Trombocitopenia/terapia , Trombose/prevenção & controle , Anticorpos Antifosfolipídeos/sangue , Hemorragia/etiologia , Humanos , Receptores de Trombopoetina/agonistas , Trombocitopenia/sangue , Trombocitopenia/imunologia , Trombose/etiologia
12.
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
13.
Hematology Am Soc Hematol Educ Program ; 2019(1): 426-432, 2019 12 06.
Artigo em Inglês | MEDLINE | ID: mdl-31808842

RESUMO

Antiphospholipid syndrome (APS) is a systemic autoimmune disorder characterized by thrombosis, pregnancy morbidity, or nonthrombotic manifestations in patients with persistently positive antiphospholipid antibodies (aPL). Conventional APS treatment focuses on antithrombotic strategies, which are usually ineffective for the microvascular and nonthrombotic manifestations of aPL. Using a case-based presentation, this review focuses on the role of immunosuppression in nonobstetric APS, including B-cell inhibition (rituximab, belimumab, and bortezomib), complement inhibition (eculizumab), mechanistic target of rapamycin inhibition (sirolimus), vascular endothelial cell modulation (defibrotide), statins, and traditional rheumatologic disease-modifying agents (hydroxychloroquine, mycophenolate mofetil, azathioprine, and cyclophosphamide).


Assuntos
Síndrome Antifosfolipídica/tratamento farmacológico , Imunossupressão , Imunossupressores/uso terapêutico , Anticorpos Antifosfolipídeos/imunologia , Síndrome Antifosfolipídica/imunologia , Síndrome Antifosfolipídica/patologia , Humanos , Masculino , Pessoa de Meia-Idade
14.
Biomedica ; 39(4): 673-688, 2019 12 01.
Artigo em Inglês, Espanhol | MEDLINE | ID: mdl-31860179

RESUMO

Introduction: The antiphospholipid syndrome is characterized by the persistent presence of antiphospholipid antibodies and clinical manifestations of thrombosis or gestational morbidity that are associated with oxidative stress and endothelial dysfunction. Objective: To evaluate markers of oxidative stress in endothelial cells induced by the serum from women with different clinical manifestations of the antiphospholipid syndrome, and to analyze the antioxidant capacity of the sera. Materials and methods: We included 48 women who were classified as follows: presence of antiphospholipid antibodies and clinical criteria of gestational morbidity alone, vascular thrombosis only, and gestational morbidity/vascular thrombosis. Control groups included antiphospholipid antibodies negative women. In an in vitro model of endothelial cells stimulated with sera from women included in the groups, some markers of oxidative stress were determined by flow cytometry. The antioxidant capacity in the sera of these women was analyzed. Results: The sera from the groups of women with antiphospholipid syndrome that presented thrombosis, with or without gestational morbidity, generated a significant increase (p<0.05 and p<0.001) in endothelial oxidative stress markers in contrast to the control of normal human serum. There were no differences in the effect of the sera from the different study groups on endothelial lipid peroxidation. Also, there was also no difference in the antioxidant activity of the sera. Conclusion: Mitochondrial oxidative stress in the endothelium is associated with the presence of thrombosis; instead, its association with gestational morbidity generates intracellular oxidative stress.


Assuntos
Anticorpos Antifosfolipídeos/imunologia , Síndrome Antifosfolipídica/imunologia , Células Endoteliais/metabolismo , Estresse Oxidativo/imunologia , Soro/imunologia , Adulto , Síndrome Antifosfolipídica/complicações , Biomarcadores/metabolismo , Estudos de Casos e Controles , Sobrevivência Celular , Feminino , Humanos , Peroxidação de Lipídeos , Gravidez , Complicações na Gravidez/imunologia , Espécies Reativas de Oxigênio/metabolismo , Soro/metabolismo , Superóxidos/metabolismo , Trombose/etiologia , Trombose/imunologia , Veias Umbilicais/citologia
15.
Immunol Res ; 67(6): 478-485, 2019 12.
Artigo em Inglês | MEDLINE | ID: mdl-31873844

RESUMO

Extra-criteria manifestations such as thrombocytopenia and livedo are described associated with antiphospholipid syndrome (APS) but are not included in the current classification criteria. Their clinical expression might be important, as they may be associated with a high-risk profile of antiphospholipid antibodies (aPL) and thrombosis. We evaluated the association between the presence of extra-criteria manifestations in primary obstetric-APS (POAPS) and aPL profiles. We also evaluated whether the presence of extra-criteria manifestations in POAPS patients increases the risk of developing thrombosis during the follow-up period (median follow-up 5 years; range 3-9 years). We selected 79 women who were included in our study only if they were first diagnosed with POAPS (with no history of previous thrombosis) and reevaluated for the presence of thrombosis after the follow-up period. We evaluated the association between the aPL profile and extra-criteria manifestations. We also evaluated the relationship of thrombosis during the follow-up period with extra-criteria manifestations and other risk factors. Patients with three or more extra-criteria manifestations presented high rates of triple positivity for the aPL profile (75%) (p < 0.001). We also found a relationship between the presence of extra-criteria manifestations and the presence of high titers of aPL: 91.7% of patients with three or more extra-criteria manifestations had high titers of aPL (p < 0.01). We further evaluated the group of POAPS patients according to thrombotic events during the follow-up. Among these patients, 6 (7.6%) presented thrombosis. Notably, 100% of patients with a thrombotic event during the follow-up had more than three extra-criteria manifestations. POAPS patients with extra-criteria manifestations might have a high-risk aPL profile and a major risk of developing thrombosis.


Assuntos
Anticorpos Antifosfolipídeos/imunologia , Síndrome Antifosfolipídica/imunologia , Trombose/imunologia , Adulto , Feminino , Humanos , Gravidez , Fatores de Risco
16.
Zhonghua Nei Ke Za Zhi ; 58(12): 894-898, 2019 Dec 01.
Artigo em Chinês | MEDLINE | ID: mdl-31775452

RESUMO

Objective: Portal vein thrombosis (PVT) is a rare and severe clinical manifestation of antiphospholipid syndrome (APS), as well as a predictor of poor prognosis. This study was conducted to explore the clinical features and risk factors of PVT in APS patients. Methods: A total of 123 APS patients diagnosed from 2012 to 2019 were retrospectively enrolled. The diagnosis of PVT was made according to the 2009 American College of Liver Diseases (AASLD) criteria. Clinical and laboratory data were collected. A multivariate (MV) logistic regression model was constructed using a stepwise forward selection procedure among those candidate univariables with P values<0.10. Results: A total of 28 cases with PVT, and 95 control cases without PVT were finally enrolled.The 28 APS-PVT patients included 5 males and 23 females with age range from 17 to 63 years. Clinical manifestations included acute thrombosis in 8 patients, chronic thrombosis in 16, and 4 with portal vein spongiform. As to the involved vessels, single portal vein thrombosis was seen in 20 patients, portal combined with superior mesenteric vein (SMV) and splenic vein in one patient, portal plus SMV in 4 and only SMV in 3 patients. Other manifestations were portal hypertension (16/28), esophageal varices (13/28), spleen infarction (7/28) and gastrointestinal bleeding (4/28). Two antiphospholipid antibodies were positive in 13 cases. Triple positive antibodies were seen in 7 cases. Multivariate logistic regression analysis showed that disease duration less than 0.5 years (OR=72.74, 95%CI 7.50-705.45, P<0.001), hypoalbuminemia (OR=356.45, 95%CI 19.19-6 620.14, P<0.001), and elevated erythrocyte sedimentation rate (ESR)/C-reactive protein (CRP) (OR=14.41, 95%CI 1.49-139.20, P<0.001) were independent risk factors for PVT in APS. Conclusion: PVT is usually misdiagnosed due to insidious onset. Short disease duration, hypoalbuminemia and elevated ESR/CRP are risk factors for PVT in APS. Better understanding, early diagnosis and treatment will improve the clinical outcome.


Assuntos
Anticorpos Antifosfolipídeos/imunologia , Síndrome Antifosfolipídica/imunologia , Cirrose Hepática/imunologia , Veia Porta/patologia , Trombose/imunologia , Trombose Venosa/fisiopatologia , Adolescente , Adulto , Síndrome Antifosfolipídica/complicações , Feminino , Humanos , Cirrose Hepática/complicações , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Fatores de Risco , Trombose/complicações , Trombose Venosa/complicações , Adulto Jovem
17.
Biochemistry (Mosc) ; 84(9): 992-1007, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31693459

RESUMO

The review discusses the mechanisms of participation of natural killer T cells (NKT cells) in the induction of antiphospholipid antibodies (APA) that play a major pathogenetic role in the formation of antiphospholipid syndrome (APS), summarizes the data on APS pathogenesis, and presents modern concepts on the antibody formation involving follicular helper type II NK cells.


Assuntos
Síndrome Antifosfolipídica/imunologia , Células T Matadoras Naturais/imunologia , Animais , Anticorpos Antifosfolipídeos/imunologia , Humanos
19.
Transplantation ; 103(10): 1990-2002, 2019 10.
Artigo em Inglês | MEDLINE | ID: mdl-31568231

RESUMO

Membranous nephropathy (MN) is a common cause of nephrotic syndrome after transplantation and is associated with an increased risk of allograft loss. MN may occur either as a recurrent or as a de novo disease. As in native kidneys, the pathophysiology of the MN recurrence is in most cases associated with antiphospholipid A2 receptor antibodies. However, the posttransplant course has some distinct features when compared with primary MN, including a lower chance of spontaneous remission and a greater requirement for adjuvant immunosuppressive therapy to induce complete remission. Although the efficacy of rituximab in primary MN is now well established, no randomized studies have assessed its effectiveness in MN after transplant, and there are no specific recommendations for the management of these patients. This review aims to synthesize and update the pathophysiology of posttransplant MN, as well as to address unsolved issues specific to transplantation, including the prognostic value of antiphospholipid A2 receptor, the risk of living-related donation, the link between de novo MN and rejection, and different therapeutic strategies so far deployed in posttransplant MN. Lastly, we propose a management algorithm for patients with MN who are planning to receive a kidney transplant, including pretransplant considerations, posttransplant monitoring, and the clinical approach after the diagnosis of recurrence.


Assuntos
Glomerulonefrite Membranosa/etiologia , Imunossupressores/uso terapêutico , Transplante de Rim/efeitos adversos , Complicações Pós-Operatórias/etiologia , Aloenxertos/patologia , Anticorpos Antifosfolipídeos/sangue , Anticorpos Antifosfolipídeos/imunologia , Glomerulonefrite Membranosa/diagnóstico , Glomerulonefrite Membranosa/patologia , Glomerulonefrite Membranosa/terapia , Rejeição de Enxerto/imunologia , Rejeição de Enxerto/prevenção & controle , Humanos , Rim/patologia , Complicações Pós-Operatórias/diagnóstico , Complicações Pós-Operatórias/patologia , Complicações Pós-Operatórias/terapia , Prognóstico , Receptores da Fosfolipase A2/imunologia , Recidiva , Indução de Remissão/métodos , Transplante Homólogo/efeitos adversos
20.
Lupus ; 28(12): 1460-1467, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31594451

RESUMO

Whether the presence or absence of antiphospholipid antibodies (aPL) in patients with lupus nephritis (LN) is associated with differences in clinical outcomes remains unclear. We reviewed LN patients at a single centre during 2000-2017, and compared the clinical features and long-term outcomes between patients who were seropositive or seronegative for aPL. aPL was detected in 53/149 (35.6%) patients with biopsy-proven LN, and anticardiolipin IgM, anticardiolipin IgG, anti-ß2 glycoprotein I and lupus anticoagulant was detected in 18.8%, 18.1%, 10.7% and 8.1%, respectively. Follow-up was 155.8 ± 61.0 months, and was similar between aPL-seropositive and -seronegative patients. aPL seropositivity persisted in 94.3% of patients during remission. aPL-seropositive patients showed inferior patient survival (91% and 85% at 10 and 15 years, respectively, compared to 99% and 95% in aPL-seronegative patients; p = 0.043). Nine (6.0%) patients died during follow-up, including six aPL-seropositive (four thrombotic events and two bleeding complications related to anticoagulation) and three aPL-seronegative patients. aPL seropositivity was associated with more rapid decline in estimated glomerular filtration rate (-1.44 mL/min/year compared to -0.38 mL/min/year in aPL-seronegative patients; p = 0.027) and inferior long-term renal survival (82% and 74% at 10 and 15 years, respectively, compared to 91% and 87% in aPL-seronegative patients; p = 0.034). aPL-seropositive patients also had a higher incidence of thrombotic events and miscarriage (32.1% and 13.2%, respectively, compared to 16.7% and 2.1% in the aPL-seronegative group; p = 0.030 and 0.006). We concluded that aPL seropositivity was associated with inferior long-term patient and renal survival and more frequent thrombotic events and miscarriage in LN patients.


Assuntos
Anticorpos Antifosfolipídeos/imunologia , Síndrome Antifosfolipídica/complicações , Nefrite Lúpica/sangue , Nefrite Lúpica/patologia , Aborto Espontâneo/etiologia , Adulto , Anticorpos Anticardiolipina/imunologia , Anticorpos Antifosfolipídeos/sangue , Síndrome Antifosfolipídica/diagnóstico , Síndrome Antifosfolipídica/tratamento farmacológico , Feminino , Taxa de Filtração Glomerular , Hemorragia/induzido quimicamente , Humanos , Imunossupressores/efeitos adversos , Imunossupressores/uso terapêutico , Incidência , Rim/fisiopatologia , Inibidor de Coagulação do Lúpus/sangue , Nefrite Lúpica/epidemiologia , Nefrite Lúpica/fisiopatologia , Masculino , Pessoa de Meia-Idade , Avaliação de Resultados em Cuidados de Saúde , Gravidez , Trombose/induzido quimicamente , beta 2-Glicoproteína I/sangue
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