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1.
Lupus ; 28(9): 1074-1081, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31296140

RESUMO

OBJECTIVE: The objective of this study was to analyse autoantibodies' titres modulation during belimumab treatment in 50 patients with systemic lupus erythematosus (SLE). METHODS: Sera were collected at belimumab start (T0) and every six months until the 24th month. Disease activity index (SLEDAI-2K) was analysed at every timepoint. High avidity anti-dsDNA was detected by radioimmunological method, anti-ENA, anti-cardiolipin antibodies (aCL), anti-ß2 glycoprotein I (anti-ß2GPI) were analysed by ELISA. RESULTS: Fifty patients with SLE (mean SLEDAI-2K: 7.18 ± :3), mean age of 39 ± 11 years and mean follow-up of 13 ± 7.8 years were enrolled. A significant decrease of anti-dsDNA and anti-ß2GPI IgM titres was observed at all timepoints. IgG aCL titre showed significant decrease only at T18. Anti-dsDNA negativization was detected in 21%, anti-ß2GPI IgG in 33% and aCL IgG in 30% of sera, mostly at T6. Anti-ribosomal showed a significant titre decrease at T6 and T12, with negative seroconversion at T18. Anti-Sm titre significantly dropped down at T6, then remained stable during the time. Significant correlations were found between anti-dsDNA and anti-ribosomal titre and between SLEDAI ratio (SLEDAI value/SLEDAI T0) and anti-ribosomal titre ratio (value/value T0). CONCLUSIONS: Belimumab treatment induced a significant reduction of SLE-specific autoantibodies titre and IgM anti-ß2GPI. Anti-ribosomal titre decrease correlates with anti-dsDNA titre and disease activity improvement.


Assuntos
Anticorpos Monoclonais Humanizados/administração & dosagem , Autoanticorpos/imunologia , Imunossupressores/administração & dosagem , Lúpus Eritematoso Sistêmico/tratamento farmacológico , Adulto , Anticorpos Anticardiolipina/imunologia , Anticorpos Antinucleares/imunologia , Anticorpos Monoclonais Humanizados/farmacologia , Fator Ativador de Células B/imunologia , Seguimentos , Humanos , Imunoglobulina G/imunologia , Imunossupressores/farmacologia , Lúpus Eritematoso Sistêmico/imunologia , Lúpus Eritematoso Sistêmico/fisiopatologia , Pessoa de Meia-Idade , Estudos Retrospectivos , Índice de Gravidade de Doença , beta 2-Glicoproteína I/imunologia
2.
Zhonghua Nei Ke Za Zhi ; 58(7): 496-500, 2019 Jul 01.
Artigo em Chinês | MEDLINE | ID: mdl-31269565

RESUMO

Antiphospholipid antibodies (aPLs) are a group of autoantibodies that target phospholipids and/or phospholipid-binding proteins. aPLs are important serum markers of anti phospholipid syndrome and are also risk factors for thrombosis and pathological pregnancy. Standardization of aPLs detection is critical to its clinical application.


Assuntos
Anticorpos Antifosfolipídeos/sangue , Síndrome Antifosfolipídica/diagnóstico , Trombose/imunologia , Anticorpos Anticardiolipina/sangue , Anticorpos Anticardiolipina/imunologia , Anticorpos Antifosfolipídeos/imunologia , Síndrome Antifosfolipídica/sangue , Síndrome Antifosfolipídica/imunologia , Biomarcadores/sangue , Consenso , Feminino , Humanos , Gravidez , Trombose/prevenção & controle , beta 2-Glicoproteína I
3.
Hum Antibodies ; 27(2): 135-141, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30856108

RESUMO

BACKGROUND: Extractable nuclear antigen (ENA) and anti-double stranded DNA (anti-dsDNA) positivity and related diseases like systemic lupus erythematosus, Sjögren syndrome, and other autoimmune diseases are known to be associated with obstetrical complications and poor perinatal outcomes. OBJECTIVE: To demonstrate the importance of ENA, anti-dsDNA, antiphospholipid (APL), and anticardiolipin (ACL) antibody positivity on pregnancy outcomes. METHODS: Ninety one pregnant women with known ENA, anti-dsDNA, APL IgG and IgM, and ACL IgG and IgM antibody positivity were retrospectively compared with 91 randomly selected pregnant woman in terms of obstetrical complications and pregnancy outcomes. Beksac Obstetrics Index-pregnancy (BOIp), calculated as (number of children + (π/10))/gravidity in the current pregnancy, was used to compare the risk level between groups. RESULTS: Significant differences were found in the median maternal age, gravidity, number of previous miscarriages, and BOIp between the groups (p= 0.04, p< 0.001, p< 0.001, and p< 0.001, respectively). Significant differences were also found between the study and control groups in the median gestational age at birth, birth weight, and APGAR1 score (p< 0.001 for all). Similarly, significant differences were found between groups in the rates of intra-uterine growth restriction, oligohydramnios, and gestational hypertension (p< 0.001, p= 0.05, and p= 0.05, respectively). There were 3 (3.3%) stillbirths in the study group and none in the control group (p= 0.123). CONCLUSION: We evaluated the impact of anti-dsDNA, ENA, APL, and ACL antibody positivity, which may cause immunologic inflammation at placenta and thereby affect pregnancy outcomes.


Assuntos
Anticorpos Anticardiolipina/imunologia , Anticorpos Antifosfolipídeos/imunologia , Antígenos Nucleares/imunologia , Complicações na Gravidez/imunologia , RNA de Cadeia Dupla/imunologia , Aborto Espontâneo/imunologia , Adulto , Síndrome Antifosfolipídica/imunologia , Doenças Autoimunes/imunologia , Feminino , Retardo do Crescimento Fetal/imunologia , Idade Gestacional , Humanos , Imunoglobulinas/imunologia , Inibidor de Coagulação do Lúpus/imunologia , Lúpus Eritematoso Sistêmico/imunologia , Placenta/imunologia , Gravidez , Resultado da Gravidez , Estudos Retrospectivos , Fatores de Risco , Natimorto , Adulto Jovem
4.
Clin Rheumatol ; 38(3): 885-893, 2019 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-30515663

RESUMO

OBJECTIVE: To validate the association of thrombotic events with positive lupus anticoagulant (LA) and co-presence of anti-RNP/Sm, as well as the diagnostic accuracy of this combination of antibodies for thrombosis. METHODS: Case-control study of patients with systemic lupus erythematosus (SLE) who presented thrombosis after SLE diagnosis and controls with SLE without thrombosis. Comorbidities, traditional risk factors, clinical variables, and treatment were evaluated. Antiphospholipid (aPL) and anti-RNP/Sm antibodies were determined. RESULTS: Sixty-three cases and 63 controls were studied, 88% women, median age of 40 years, and disease duration of 135 months at study inclusion. No differences were found between groups regarding age, comorbidities, or clinical characteristics at SLE diagnosis. Patients with thrombosis were more frequently positive for anti-RNP/Sm (p = 0.001), IgG aCL (p = 0.02), IgG anti-B2GPI (p = 0.02), IgM anti-B2GPI (p = 0.02), LA (p < 0.001), the combination of anti-RNP/Sm + LA (p < 0.001), and aPL triple marker (p = 0.002), compared to controls. The combination of anti-RNP/Sm + LA, SLEDAI-2 K, and prednisone dose was associated with thrombosis (p < 0.05). The combination of anti-RNP/Sm + LA showed 56% sensitivity, 79% specificity, 73% positive predictive value, 64% negative predictive value, positive likelihood ratio (LR) 2.69, and negative LR 0.56 for predicting thrombosis. No difference was found in the comparison of area under the curve between LA alone and the combination of anti-RNP/Sm + LA (p = 0.73). CONCLUSION: Thrombosis was associated with disease activity, dose of prednisone, and the combination of anti-RNP/Sm antibodies and LA. This combination of antibodies could be useful in the identification of SLE patients at risk of thrombosis.


Assuntos
Inibidor de Coagulação do Lúpus/imunologia , Lúpus Eritematoso Sistêmico/imunologia , Trombose/imunologia , Proteínas Centrais de snRNP/imunologia , Adolescente , Adulto , Anticorpos Anticardiolipina/imunologia , Anticorpos Antinucleares/imunologia , Anticorpos Antifosfolipídeos/imunologia , Autoanticorpos/imunologia , Estudos de Casos e Controles , Feminino , Glucocorticoides/administração & dosagem , Humanos , Imunoglobulina G/imunologia , Modelos Logísticos , Lúpus Eritematoso Sistêmico/tratamento farmacológico , Lúpus Eritematoso Sistêmico/epidemiologia , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Prednisona/administração & dosagem , Fatores de Risco , Trombose/epidemiologia , Adulto Jovem , beta 2-Glicoproteína I/imunologia
5.
Arthritis Rheumatol ; 71(2): 281-289, 2019 02.
Artigo em Inglês | MEDLINE | ID: mdl-30375754

RESUMO

OBJECTIVE: To determine, in a large, multiethnic/multiracial, prospective inception cohort of patients with systemic lupus erythematosus (SLE), the frequency, attribution, clinical, and autoantibody associations with lupus psychosis and the short- and long-term outcomes as assessed by physicians and patients. METHODS: Patients were evaluated annually for 19 neuropsychiatric (NP) events including psychosis. Scores on the Systemic Lupus Erythematosus Disease Activity Index 2000, the Systemic Lupus International Collaborating Clinics/American College of Rheumatology Damage Index, and the Short Form 36 (SF-36) were recorded. Time to event and linear regressions were used as appropriate. RESULTS: Of 1,826 SLE patients, 88.8% were female and 48.8% were Caucasian. The mean ± SD age was 35.1 ± 13.3 years, the mean ± SD disease duration was 5.6 ± 4.2 months, and the mean ± SD follow-up period was 7.4 ± 4.5 years. There were 31 psychotic events in 28 of 1,826 patients (1.53%), and most patients had a single event (26 of 28 [93%]). In the majority of patients (20 of 25 [80%]) and events (28 of 31 [90%]), psychosis was attributed to SLE, usually either in the year prior to or within 3 years of SLE diagnosis. Positive associations (hazard ratios [HRs] and 95% confidence intervals [95% CIs]) with lupus psychosis were previous SLE NP events (HR 3.59 [95% CI 1.16-11.14]), male sex (HR 3.0 [95% CI 1.20-7.50]), younger age at SLE diagnosis (per 10 years) (HR 1.45 [95% CI 1.01-2.07]), and African ancestry (HR 4.59 [95% CI 1.79-11.76]). By physician assessment, most psychotic events resolved by the second annual visit following onset, in parallel with an improvement in patient-reported SF-36 summary and subscale scores. CONCLUSION: Psychosis is an infrequent manifestation of NPSLE. Generally, it occurs early after SLE onset and has a significant negative impact on health status. As determined by patient and physician report, the short- and long-term outlooks are good for most patients, although careful follow-up is required.


Assuntos
Vasculite Associada ao Lúpus do Sistema Nervoso Central/epidemiologia , Transtornos Psicóticos/epidemiologia , Adulto , Fatores Etários , Anticorpos Anticardiolipina/imunologia , Autoanticorpos/imunologia , Estudos de Coortes , Feminino , Humanos , Estimativa de Kaplan-Meier , Modelos Lineares , Inibidor de Coagulação do Lúpus/imunologia , Lúpus Eritematoso Sistêmico/epidemiologia , Lúpus Eritematoso Sistêmico/imunologia , Vasculite Associada ao Lúpus do Sistema Nervoso Central/imunologia , Masculino , Pessoa de Meia-Idade , Modelos de Riscos Proporcionais , Estudos Prospectivos , Transtornos Psicóticos/imunologia , Receptores de N-Metil-D-Aspartato/imunologia , Fatores Sexuais , Adulto Jovem , beta 2-Glicoproteína I/imunologia
6.
Stroke ; 49(11): 2770-2772, 2018 11.
Artigo em Inglês | MEDLINE | ID: mdl-30355196

RESUMO

Background and Purpose- International classification criteria for antiphospholipid syndrome (APS) include IgM (immunoglobulin M), aCL (anticardiolipin), and aB2GPI (anti-ß2-glycoprotein-I) antibodies, but their relevance is still debated. We aimed to assess whether patients with isolated IgM aCL and/or aB2GPI at diagnosis have specific characteristics and outcomes. Methods- We retrospectively included APS patients with isolated IgM antiphospholipid antibodies (isolated-IgM-APS) and compared them to APS patients with IgG and IgM, or IgG alone and/or lupus anticoagulant (nonisolated-IgM-APS). Results- Among the 168 APS patients included, 24 (14.3%) had isolated IgM. Median follow-up was 92.5 months (36-151.5). Isolated-IgM-APS patients were 9.5 years older. At diagnosis, stroke was more frequent in isolated-IgM-APS after adjustment for cardiovascular risk factors (odds ratio, 3.8; 95% CI, 1.3-11.5). IgM isotype remained isolated in 17 of 24 (70.8%) patients over time. Global relapse-free survival did not differ between the two groups. In thrombotic APS, monotherapy with antiplatelet agents was more frequently used in isolated-IgM-APS group with 14 of 20 versus 28 of 134 patients ( P<0.0001), with a higher relapse rate with antiplatelet agent alone compared to vitamin K antagonists, especially for patients presenting with a stroke (hazard ratio, 7.37; 95% CI, 1.19-19.0). Conclusions- Isolated IgM APS patients should not be disregarded because they represent 14.3% of an APS population. They have some characteristics: older age at diagnosis and a strong association with stroke. Clinicians must be aware of this situation because antiplatelet agent do not seem to well prevent relapses compared to vitamin K antagonist.


Assuntos
Anticorpos Anticardiolipina/imunologia , Síndrome Antifosfolipídica/imunologia , Imunoglobulina M/imunologia , Acidente Vascular Cerebral/imunologia , beta 2-Glicoproteína I/imunologia , Adulto , Anticoagulantes/uso terapêutico , Síndrome Antifosfolipídica/tratamento farmacológico , Síndrome Antifosfolipídica/epidemiologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Inibidores da Agregação de Plaquetas/uso terapêutico , Acidente Vascular Cerebral/epidemiologia
7.
Clin Exp Immunol ; 194(1): 27-38, 2018 10.
Artigo em Inglês | MEDLINE | ID: mdl-30208508

RESUMO

Immunoglobulin (Ig) G- and IgM-class anti-cardiolipin antibodies (aCL) and lupus anti-coagulant (LA) are included in the 1997 update of the American College of Rheumatology (ACR-97) systemic lupus erythematosus (SLE) criteria. Despite limited evidence, IgA-aCL and IgA anti-ß2 -glycoprotein-I (anti-ß2 GPI) were included in the 2012 Systemic Lupus International Collaborating Clinics criteria. The present study aimed to evaluate IgG-/IgA-/IgM-aCL and anti-ß2 GPI occurrence in relation to disease phenotype, smoking habits, pharmacotherapy, anti-phospholipid syndrome (APS) and organ damage among 526 Swedish SLE patients meeting ACR-97. Patients with rheumatoid arthritis (n = 100), primary Sjögren's syndrome (n = 50) and blood donors (n = 507) served as controls. Anti-phospholipid antibodies (aPL) were analysed by fluoroenzyme-immunoassays detecting aCL/anti-ß2 GPI. Seventy-six (14%) SLE cases fulfilled the Sydney APS-criteria, and ≥ 1 aCL/anti-ß2 GPI isotype (IgG/IgA/IgM) occurred in 138 SLE patients (26%). Forty-five (9%) of the SLE cases had IgA-aCL, 20 of whom (4%) lacked IgG-/IgM-aCL. Seventy-four (14%) tested positive for IgA anti-ß2 GPI, 34 (6%) being seronegative regarding IgG/IgM anti-ß2 GPI. Six (1%) had APS manifestations but were seropositive regarding IgA-aCL and/or IgA anti-ß2 GPI in the absence of IgG/IgM-aPL and LA. Positive LA and IgG-aPL tests were associated with most APS-related events and organ damage. Exclusive IgA anti-ß2 GPI occurrence associated inversely with Caucasian ethnicity [odds ratio (OR) = 0·21, 95% confidence interval (CI) = 0·06-0·72) and photosensitivity (OR = 0·19, 95% CI = 0·05-0·72). Nephritis, smoking, LA-positivity and statin/corticosteroid-medication associated strongly with organ damage, whereas hydroxychloroquine-medication was protective. In conclusion, IgA-aPL is not rare in SLE (16%) and IgA-aPL analysis may have additional value among SLE cases with suspected APS testing negative for other isotypes of aPL and LA.


Assuntos
Anticorpos Anticardiolipina/sangue , Anticorpos Antifosfolipídeos/sangue , Imunoglobulina A/sangue , Imunoglobulina G/sangue , Imunoglobulina M/sangue , Lúpus Eritematoso Sistêmico/sangue , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Anticorpos Anticardiolipina/imunologia , Anticorpos Antifosfolipídeos/imunologia , Artrite Reumatoide/sangue , Estudos Transversais , Feminino , Humanos , Hidroxicloroquina/uso terapêutico , Imunoglobulina A/imunologia , Imunoglobulina G/imunologia , Imunoglobulina M/imunologia , Lúpus Eritematoso Sistêmico/tratamento farmacológico , Lúpus Eritematoso Sistêmico/imunologia , Masculino , Pessoa de Meia-Idade , Nefrite/imunologia , Nefrite/patologia , Síndrome de Sjogren/sangue , Suécia , Adulto Jovem
8.
Immunobiology ; 223(12): 772-776, 2018 12.
Artigo em Inglês | MEDLINE | ID: mdl-30115377

RESUMO

Protein Z (PZ) is a vitamin K-dependent protein involved in the down-regulation of coagulation by forming a complex with the protein Z-dependent protease inhibitor. The complex inhibits the activated factor X on phospholipid surface. Presence of anti-PZ (aPZ) antibodies was first described in women with pathological pregnancies but the significance of aPZ antibodies in other pathological situations was poorly studied. In this work we analyzed the frequency of aPZ antibodies in a series of 86 consecutive patients with anticardiolipin (aCL) antibodies and studied the association of aPZ with other antiphospholipid (aPL) antibodies [lupus anticoagulant (LAC) and anti-ß2GP-1 antibodies] and the clinical signification of these aPZ antibodies in term of thrombosis or fetal loss. Anti-PZ antibodies (IgG and IgM) were detected using commercially available ELISA assays. The frequency of aPZ antibodies was 40.7% in the patient group versus 6.8% in a group of 59 healthy volunteers (p < 0.0001). The frequency of aPZ antibodies significantly increases (p < 0.05) in patients with a double or triple positivity of aPL antibodies and a higher frequency of aPZ antibodies was observed in patients with LAC (57.7%) than in patients without LAC (25.6%, p = 0.02). There were no significant differences in aPZ antibodies frequency between patients with and without thrombotic events. Interestingly, among the 8 women with recurrent foetal losses, aPZ antibodies were observed in 7 cases, in agreement with previous observations suggesting that aPZ antibodies may be associated with obstetrical complications.


Assuntos
Anticorpos Anticardiolipina/imunologia , Autoanticorpos/imunologia , Proteínas Sanguíneas/imunologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Síndrome Antifosfolipídica/diagnóstico , Síndrome Antifosfolipídica/imunologia , Proteínas Sanguíneas/antagonistas & inibidores , Feminino , Humanos , Imunoglobulina G/sangue , Imunoglobulina G/imunologia , Imunoglobulina M/sangue , Imunoglobulina M/imunologia , Lúpus Eritematoso Sistêmico/diagnóstico , Lúpus Eritematoso Sistêmico/imunologia , Masculino , Pessoa de Meia-Idade , Adulto Jovem
9.
Clin Immunol ; 194: 92-99, 2018 09.
Artigo em Inglês | MEDLINE | ID: mdl-30017909

RESUMO

Patients with antiphospholipid antibodies (APLA) are predisposed to develop thrombosis, however the standardization of anti-cardiolipin (aCL) and anti-beta 2 glycoprotein I (ß2-GPI) Ab assays are challenging. Therefore we decided to test the performance of a new chemiluminescent assay (CLIA), and assayed aCL and aß2-GPI IgG/M in serum from 120 healthy individuals, 108 patients with idiopathic venous thrombosis, 78 patients with antiphospholipid syndrome (APS), and 64 non-thrombotic APLA-carriers using CLIA IDS-iSYS. Very good (aCL/aß2-GPI IgG) to moderate (aCL/aß2-GPI IgM) agreement with a commercial and an in house ELISA assay were observed and, in particular, CLIA demonstrated the highest sensitivity in aß2-GPI IgG detection. Finally, aCL/aß2-GPI Ab capacity to predict the thrombotic risk was tested showing for CLIA a significant odds ratio (OR) when considering double positivity for aCL/aß2-GPI IgG, aCL IgG at high levels, and aß2-GPI IgG at high levels. In conclusion, CLIA improves aß2-GPI IgG detection and thrombotic risk assessment.


Assuntos
Anticorpos Anticardiolipina/imunologia , Autoanticorpos/imunologia , Cardiolipinas/imunologia , Trombose/imunologia , beta 2-Glicoproteína I/imunologia , Anticorpos Antifosfolipídeos/imunologia , Síndrome Antifosfolipídica/imunologia , Feminino , Humanos , Imunoglobulina G/imunologia , Medições Luminescentes/métodos , Masculino , Pessoa de Meia-Idade , Razão de Chances , Medição de Risco
10.
Clin Rheumatol ; 37(12): 3359-3364, 2018 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-29948348

RESUMO

Vascular antiphospholipid syndrome (VAPS) and obstetric (OAPS) are different entities because some patients only develop thrombosis (without recurrent pregnancy losses) and vice versa. Only two articles have reported that low 25-hydroxy-cholecalciferol (vitamin D3, VD3) levels were not correlated with the presence of conventional antiphospholipid antibodies (aPL Abs: anticardiolipin (aCL), anti-beta2glycoprotein I (aß2gpI), and lupus anticoagulant (LA)), but no article analyzed the association of VD3 and anti-annexin A5 (aanxA5) Abs. The aim of our study was to investigate the association between VD3, multiple positivity of conventional aPL and aanxA5 Abs levels only in female OAPS vs. VAPS. Our study included 62 consecutive female PAPS patients. Concentrations of Abs were measured by ELISA, while VD3 levels were determined by immunochemiluminescence. Only 10/62 (16.13%) had sufficient (≥ 30 ng/ml) VD3 levels, while 48/62 (77.42%) and 4/62 (6.45%) had insufficiency and VD3 deficiency, respectively. Statistically significant VD3 deficiency was noticed in VAPS (vs. OAPS, P = 0.013). A negative correlation between VD3 levels and the age of patients was noticed (r = - 0.493, P = 0.032) only in VAPS subgroup. Multiple positivity of aPL and aanxA5 Abs was not associated with VD3 deficiency. Newly emerging aPL Abs, such as aanxA5 Abs, or their combinations with classical aPL Abs are not associated with VD3 deficiency in neither OAPS nor VAPS patients. Due to its immunomodulatory roles in B-Ly homeostasis, supplementation with VD3 should be considered in APS, at least in subgroup with severe form of the disease, i.e., VAPS.


Assuntos
Anexina A5/química , Anticorpos Antifosfolipídeos/imunologia , Síndrome Antifosfolipídica/imunologia , Calcifediol/química , Aborto Habitual , Adulto , Anexina A5/imunologia , Anticorpos Anticardiolipina/imunologia , Síndrome Antifosfolipídica/sangue , Calcifediol/imunologia , Cardiolipinas/imunologia , Colecalciferol/sangue , Colecalciferol/deficiência , Feminino , Humanos , Imunoglobulina G/imunologia , Imunoglobulina M/imunologia , Inibidor de Coagulação do Lúpus/imunologia , Pessoa de Meia-Idade , Gravidez , Estudos Retrospectivos , Trombose/imunologia , Trombose/patologia , beta 2-Glicoproteína I/imunologia
11.
Clin Chim Acta ; 485: 7-13, 2018 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-29883633

RESUMO

BACKGROUND: We assessed the performance characteristics and correlations of the traditional enzyme-linked immunosorbent assay (ELISA) and chemiluminescence immunoassay (CIA) for detecting IgG and IgM antibodies to cardiolipin (aCL) and beta2 glycoprotein (anti-ß2GPI) antibodies in patients under routine evaluation for APS. METHODS: Patients (n = 216) referred to ARUP Laboratories for lupus anticoagulant (LAC) and/or aCL or anti-ß2GPI IgG/IgM antibodies evaluation were assessed by ELISA and CIA methods. Diagnostic accuracies, correlations between methods and specific clinical manifestations in APS were investigated. RESULTS: The areas under the curve (%) for APS using LAC with CIA (74, 95% CI: 65-82) or ELISA (70, 95% CI: 61-79) aPLs were comparable. The overall agreements and linear regression correlations between methods for aPL antibody of the same specificity were variable: aCL IgG 87.3%; R2 = 0.7491, aCL IgM 71.6%; R2 = 0.2656, anti-ß2GPI IgG 77.2%; R2 = 0.7688 and anti-ß2GPI IgM 81.7%; R2 = 0.3305. CONCLUSIONS: With inclusion of LAC, the ELISA and CIA show comparable performance for the diagnosis of APS. However, correlations of APS-specific manifestations were dependent on method of detecting the aPL antibodies suggesting platforms may not be used interchangeable.


Assuntos
Anticorpos Anticardiolipina/análise , Síndrome Antifosfolipídica/diagnóstico , Síndrome Antifosfolipídica/imunologia , beta 2-Glicoproteína I/análise , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Anticorpos Anticardiolipina/imunologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Adulto Jovem , beta 2-Glicoproteína I/imunologia
12.
Int J Gynaecol Obstet ; 142(2): 214-220, 2018 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-29676461

RESUMO

OBJECTIVE: To assess outcomes after 20 weeks of pregnancy according to autoantibody profile and clinical presentation of maternal antiphospholipid syndrome (APS). METHODS: The present retrospective cohort analysis included women diagnosed with APS at a tertiary medical center in Israel between January 1, 2012, and December 31, 2016. Anticardiolipin antibodies, anti-ß2-glycoprotein antibodies, and lupus anticoagulant were assessed. Participants were stratified by type of APS (obstetric vs thrombotic), antibody profile, and antibody titer (low vs high). Primary composite outcomes were rated as severe (stillbirth, fetal growth restriction at <34 weeks, severe pre-eclampsia, or delivery at <32 weeks) and mild (stillbirth, any fetal growth restriction, any pre-eclampsia, or delivery at <34 weeks). RESULTS: A total of 99 women were included in the analysis. The primary composite outcomes were similar regardless of stratification. Lupus anticoagulant positivity was associated with delivery before 37 weeks. When compared with low antibody titer, high antibody titer was associated delivery at or before 32 weeks (P=0.045) and 34 weeks (P=0.029). CONCLUSION: High antibody titer might be associated with an increased risk of severe prematurity among pregnant women with APS.


Assuntos
Síndrome Antifosfolipídica/imunologia , Retardo do Crescimento Fetal/imunologia , Pré-Eclâmpsia/imunologia , Complicações na Gravidez/imunologia , Nascimento Prematuro/imunologia , Adulto , Anticorpos Anticardiolipina/sangue , Anticorpos Anticardiolipina/imunologia , Síndrome Antifosfolipídica/sangue , Autoanticorpos/sangue , Autoanticorpos/imunologia , Feminino , Humanos , Recém-Nascido de Baixo Peso/imunologia , Israel , Inibidor de Coagulação do Lúpus/sangue , Inibidor de Coagulação do Lúpus/imunologia , Gravidez , Complicações na Gravidez/sangue , Resultado da Gravidez , Glicoproteínas beta 1 Específicas da Gravidez/análise , Glicoproteínas beta 1 Específicas da Gravidez/imunologia , Estudos Retrospectivos , Natimorto , Adulto Jovem
13.
Nephrol Dial Transplant ; 33(4): 709-716, 2018 04 01.
Artigo em Inglês | MEDLINE | ID: mdl-29346631

RESUMO

Background: In kidney transplant recipients, anticardiolipin (ACL) antibodies without antiphospholipid syndrome (APS) are found in up to 38% of patients and could be associated with thrombotic events (TEs). However, the prognostic role of ACL regarding kidney transplant and patients outcomes have still not been well defined. Methods: We conducted an observational, monocentric, retrospective cohort study including 446 kidney transplant recipients and standardized follow-up: 36-month allograft and patient survival, 12-month estimated glomerular filtration rate (eGFR) and 3- and 12-month screening biopsies. Results: ACL tests were run on 247 patients, 101 were positive (ACL+ group, 41%) and 146 were negative (ACL- group, 59%). Allografts and patient survival within 36 months as TE were similar between both groups [hazard ratio (HR) = 1.18 and HR = 0.98, respectively]. The 12-month eGFR was significantly lower in the ACL+ group [median (95% confidence interval) 48.5 (35.1-60.3) versus 51.9 (39.1-65.0) mL/min/1.73 m2, P= 0.042]. ACL+ was independently associated with eGFR decrease (P = 0.04). In 12-month screening biopsies, tubular atrophy was significantly more severe in the ACL+ group compared with the ACL- group (P = 0.02). Conclusions: ACL without APS before kidney transplantation is an independent risk factor of eGFR decline within the first year post-transplant without over-incidence of TEs. Specific immunosuppressive therapy including mammalian target of rapamycin inhibitors should be discussed in the future.


Assuntos
Anticorpos Anticardiolipina/efeitos adversos , Taxa de Filtração Glomerular , Rejeição de Enxerto/etiologia , Sobrevivência de Enxerto , Nefropatias/cirurgia , Transplante de Rim/efeitos adversos , Adulto , Anticorpos Anticardiolipina/sangue , Anticorpos Anticardiolipina/imunologia , Feminino , Rejeição de Enxerto/sangue , Rejeição de Enxerto/patologia , Humanos , Nefropatias/sangue , Nefropatias/imunologia , Masculino , Pessoa de Meia-Idade , Prognóstico , Estudos Retrospectivos , Fatores de Risco , Taxa de Sobrevida , Transplantados
14.
Lupus ; 27(2): 225-234, 2018 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-28659045

RESUMO

The objective of this study is to identify the effects of statins and risk factors for thrombosis in patients with new onset of systemic lupus erythematosus (SLE) with or without antiphospholipid antibodies (aPL). Consecutive patients with SLE without history of thrombotic events were retrospectively enrolled from April 1997 to February 2014. The development of first thrombosis and death caused by thrombosis were defined as the study endpoint. Risk and protective factors for developing thrombosis were analyzed. A total of 152 patients, 80 positive and 72 negative for aPL, were included. In aPL-positive patients, 15 developed arterial ( n = 6) and venous ( n = 9) thrombosis (median follow-up period 69 months). Cox's proportional hazards model showed that older age at SLE onset and IgG-anticardiolipin antibodies (aCL) were statistically significant risks for thrombosis. Statin therapy was identified as a statistically significant protective factor against thrombosis (hazard ratio 0.12, 95% confidence interval 0.01-0.98). In aPL-negative patients (median follow-up period 46 months), seven patients developed thrombosis (five arterial and two venous). No risk factors for thrombosis were found in this group. In aPL-positive patients with SLE, the late disease onset and the presence of IgG-aCL represented additional risk factors for thrombosis. Statin treatment appeared as a protective factor for thrombosis.


Assuntos
Inibidores de Hidroximetilglutaril-CoA Redutases/farmacologia , Lúpus Eritematoso Sistêmico/complicações , Trombose/tratamento farmacológico , Trombose/etiologia , Adulto , Anticorpos Anticardiolipina/imunologia , Anticorpos Antifosfolipídeos/imunologia , Feminino , Humanos , Inibidores de Hidroximetilglutaril-CoA Redutases/administração & dosagem , Inibidores de Hidroximetilglutaril-CoA Redutases/uso terapêutico , Japão/epidemiologia , Lúpus Eritematoso Sistêmico/diagnóstico , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Fatores de Risco , Trombose/diagnóstico por imagem , Trombose/prevenção & controle
15.
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
16.
J Pak Med Assoc ; 67(7): 1004-1008, 2017 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-28770876

RESUMO

OBJECTIVE: Immune thrombocytopenia (ITP) is an immune haematologic disorder causing platelet destruction mediated by anti-platelet antibodies. In this study we aimed to evaluate the clinical and laboratory variables of ITP patients in southeast of Turkey. METHODS: In this retrospective study 167 ITP patients between 2005 and 2015 were evaluated. All patients were screened for immunological parameters including ANA (antinuclear antibodies), anti dsDNA (anti-double-stranded-DNA), ACA(anti-cardiolipin) IgM and IgG, LA (lupus anticoagulants). All patients were screened for Helicobacter pylori, HBsAg (Hepatitis B surface antigen), anti-HCV (hepatitis C virus antibody), and anti-HIV ½ (HIV antibody) and brucellosis.. RESULTS: Among the patients, 50 (29.9%) patients were male, 117 (70.1%) were female. The age range of patients was 18-86 (mean 38.16±14). In 56 patients (33.5%) splenectomy was performed. 36 patients (21.6%) were positive for ANA, 5 (3%) were positive for anti dsDNA, 14 (8.4%) for ACA Ig G, and 14 (8.4%) patients for ACA IgM. LA was tested in 165 patients and 30 (18%) patients were positive for LA. Microbiologic evaluation was as follows: 16 patients (9.6%) were positive for HbsAg, 109 (65.3%) positive for Anti-HBs, 5 positive for anti-HCV (3%), 56 (33.5%) patients were positive for Helicobacter pylori antigen, 5 (2.9%) for Brucella and one patient was positive for anti-HIV ½. CONCLUSIONS: Immune thrombocytopenia patients have to be evaluated according to their demographic characteristics and laboratory results. Secondary causes of ITP were HIV, HCV, Helicobacter pylori, brucellosis, tuberculosis, and autoimmune diseases in our region. Management of ITP patients can change in different regions.


Assuntos
Anticorpos Anticardiolipina/imunologia , Anticorpos Antinucleares/imunologia , Inibidor de Coagulação do Lúpus/imunologia , Púrpura Trombocitopênica Idiopática/imunologia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Brucelose/complicações , Brucelose/imunologia , DNA/imunologia , Feminino , Infecções por HIV/complicações , Infecções por HIV/imunologia , Infecções por Helicobacter/complicações , Infecções por Helicobacter/imunologia , Helicobacter pylori/imunologia , Hepatite B/complicações , Hepatite B/imunologia , Anticorpos Anti-Hepatite B/imunologia , Antígenos de Superfície da Hepatite B/imunologia , Hepatite C/complicações , Hepatite C/imunologia , Anticorpos Anti-Hepatite C/imunologia , Humanos , Imunoglobulina G/imunologia , Imunoglobulina M/imunologia , Masculino , Pessoa de Meia-Idade , Púrpura Trombocitopênica Idiopática/etiologia , Estudos Retrospectivos , Esplenectomia , Turquia , Adulto Jovem
17.
Arthritis Rheumatol ; 69(10): 2052-2061, 2017 10.
Artigo em Inglês | MEDLINE | ID: mdl-28666081

RESUMO

OBJECTIVE: Both environmental and genetic factors are important in the development of antiphospholipid antibodies (aPL) in patients with antiphospholipid syndrome (APS). Currently, the only available data on predisposing genetic factors have been obtained from epidemiologic studies, without mechanistic evidence. Therefore, we studied the influence of major histocompatibility complex (MHC) class II alleles on the production of aPL in a mouse model of APS. METHODS: Three groups of mice, MHC class II-deficient (MHCII-/- ) mice, MHCII-/- mice transgenic for human HLA-DQ6 (DQ6), DQ8, or DR4 alleles, and the corresponding wild-type (WT) mouse strains were immunized; half were immunized with human ß2 -glycoprotein I (ß2 GPI), and the other half were immunized with control ovalbumin (OVA) protein. Thrombus formation in vivo, tissue factor activity in carotid and peritoneal macrophages, and serum levels of tumor necrosis factor (TNF), IgG anticardiolipin (aCL), antibodies, and anti-OVA antibodies were determined. RESULTS: Immunization with ß2 GPI induced significant production of aCL and anti-ß2 GPI in WT mice compared with control mice immunized with OVA (P < 0.001) but diminished aCL (P < 0.001) and anti-ß2 GPI (P = 0.016) production in MHCII-/- mice. Anti-ß2 GPI production was fully restored in DQ6 and DQ8 mice, while levels of anti-ß2 GPI in DR4 mice and aCL in all transgenic lines were only partially restored (P < 0.001 to P < 0.046). Thrombus size in WT mice was twice that in MHCII-/- mice (P < 0.001) but similar to that in all transgenic lines. Carotid and peritoneal macrophage tissue factor levels decreased by >50% in MHCII-/- mice compared with wild-type B6 mice and were restored in DQ8 mice but not DR4 mice or DQ6 mice. TNF levels decreased 4-fold in MHCII-/- mice (P < 0.001) and were not restored in transgenic mice. CONCLUSION: Our mechanistic study is the first to show that MHC class II alleles influence not only quantitative aPL production but also the pathogenic capacity of induced aPL.


Assuntos
Anticorpos Antifosfolipídeos/imunologia , Genes MHC da Classe II/genética , Antígenos HLA-DQ/genética , Antígeno HLA-DR4/genética , Alelos , Animais , Anticorpos Anticardiolipina/imunologia , Artérias Carótidas/imunologia , Modelos Animais de Doenças , Humanos , Imunização , Imunoglobulina G/imunologia , Macrófagos/imunologia , Macrófagos Peritoneais/imunologia , Camundongos , Camundongos Knockout , Camundongos Transgênicos , Ovalbumina/imunologia , Índice de Gravidade de Doença , Trombose , Fator de Necrose Tumoral alfa/imunologia , beta 2-Glicoproteína I/imunologia
18.
Lung ; 195(4): 517-521, 2017 08.
Artigo em Inglês | MEDLINE | ID: mdl-28551717

RESUMO

The cellular immune response to Mycobacterium tuberculosis infection has been well characterized, while the humoral antibody response remains underexplored. We aimed to examine the total and anti-phospholipid IgM levels in the pleural lavage from mice with Mycobacterium bovis BCG extrapulmonary infection. We found that the levels of total and anti-phosphatidylcholine IgM antibodies remained significantly higher in infected mice as compared to non-infected mice up to day 90 after BCG infection, while the anti-cardiolipin IgM antibody levels decreased with bacteria clearance. Our findings suggest that IgM antibodies are secreted and their composition vary during early and late immune response to BCG pleurisy.


Assuntos
Anticorpos Antifosfolipídeos/imunologia , Imunidade Humoral , Imunoglobulina M/imunologia , Mycobacterium tuberculosis/imunologia , Fosfatidilcolinas/imunologia , Tuberculose Pleural/imunologia , Animais , Anticorpos Anticardiolipina/imunologia , Carga Bacteriana , Modelos Animais de Doenças , Feminino , Interações Hospedeiro-Patógeno , Masculino , Camundongos Endogâmicos C57BL , Fatores de Tempo , Tuberculose Pleural/microbiologia
19.
Clin Exp Rheumatol ; 35(4): 678-680, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-28516871

RESUMO

Catastrophic antiphospholipid syndrome (CAPS) is a severe variant of APS, characterised by clinical evidence of multiple organ involvement developing over a very short period of time, histopathological evidence of multiple small vessel occlusions and laboratory confirmation of the presence of aPL (lupus anticoagulant and/or anticardiolipin antibodies and/or anti-Beta2-glcyoprotein I antibodies). Here we report a case of a 39-year-old woman patient who developed a CAPS which was negative to the conventional aPL but positive for aPL in thin layer chromatography immunostaining and vimentin/cardiolipin antibodies by ELISA test. The patient was treated with high doses of glucocorticoids, intravenous immunoglobulins plasma exchange and immunoadsorbent apheresis with a significant improvement of the ischaemic lesions of the hands even though the necrosis of the feet progressively worsened. As a result, the patient underwent partial surgical amputation of the feet. To our knowledge, this is the first ever reported case of CAPS diagnosed by means of thin layer chromatography immunostaining and vimentin/cardiolipin antibody ELISA test.


Assuntos
Anticorpos Anticardiolipina/imunologia , Síndrome Antifosfolipídica/imunologia , Arteriopatias Oclusivas/imunologia , Vimentina/imunologia , Adulto , Amputação , Anticorpos Antifosfolipídeos/imunologia , Síndrome Antifosfolipídica/complicações , Síndrome Antifosfolipídica/diagnóstico , Síndrome Antifosfolipídica/terapia , Arteriopatias Oclusivas/diagnóstico por imagem , Arteriopatias Oclusivas/etiologia , Remoção de Componentes Sanguíneos , Cromatografia em Camada Delgada , Angiografia por Tomografia Computadorizada , Ensaio de Imunoadsorção Enzimática , Feminino , Glucocorticoides/uso terapêutico , Humanos , Imunoglobulinas Intravenosas/uso terapêutico , Fatores Imunológicos/uso terapêutico , Artéria Poplítea/diagnóstico por imagem , Artérias da Tíbia/diagnóstico por imagem
20.
Lupus ; 26(12): 1239-1251, 2017 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-28480786

RESUMO

Systemic lupus erythematosus (lupus, SLE) is a chronic autoimmune disease characterized by the production of autoantibodies, which bind to antigens and are deposited within tissues to fix complement, resulting in widespread systemic inflammation. The studies presented herein are consistent with hyperpolarized, adenosine triphosphate (ATP)-deficient mitochondria being central to the disease process. These hyperpolarized mitochondria resist the depolarization required for activation-induced apoptosis. The mitochondrial ATP deficits add to this resistance to apoptosis and also reduce the macrophage energy that is needed to clear apoptotic bodies. In both cases, necrosis, the alternative pathway of cell death, results. Intracellular constituents spill into the blood and tissues, eliciting inflammatory responses directed at their removal. What results is "autoimmunity." Ultraviolet (UV)-A1 photons have the capacity to remediate this aberrancy. Exogenous exposure to low-dose, full-body, UV-A1 radiation generates singlet oxygen. Singlet oxygen has two major palliative actions in patients with lupus and the UV-A1 photons themselves have several more. Singlet oxygen depolarizes the hyperpolarized mitochondrion, triggering non-ATP-dependent apoptosis that deters necrosis. Next, singlet oxygen activates the gene encoding heme oxygenase (HO-1), a major governor of systemic homeostasis. HO-1 catalyzes the degradation of the oxidant heme into biliverdin (converted to bilirubin), Fe, and carbon monoxide (CO), the first three of these exerting powerful antioxidant effects, and in conjunction with a fourth, CO, protecting against injury to the coronary arteries, the central nervous system, and the lungs. The UV-A1 photons themselves directly attenuate disease in lupus by reducing B cell activity, preventing the suppression of cell-mediated immunity, slowing an epigenetic progression toward SLE, and ameliorating discoid and subacute cutaneous lupus. Finally, a combination of these mechanisms reduces levels of anticardiolipin antibodies and protects during lupus pregnancy. Capping all of this is that UV-A1 irradiation is an essentially innocuous, highly manageable, and comfortable therapeutic agency.


Assuntos
Autoanticorpos/imunologia , Lúpus Eritematoso Sistêmico/radioterapia , Terapia Ultravioleta/métodos , Anticorpos Anticardiolipina/imunologia , Apoptose/imunologia , Autoimunidade , Humanos , Imunidade Celular , Lúpus Eritematoso Sistêmico/imunologia
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