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1.
BMJ Case Rep ; 13(2)2020 Feb 09.
Artigo em Inglês | MEDLINE | ID: mdl-32041760

RESUMO

A 50-year-old woman with a history of Crohn's disease treated with adalimumab presented with left hand pain and duskiness. Angiogram showed non-filling of the radial and digital arteries of the hand. Antiphospholipid antibody testing was positive, leading to a diagnosis of antitumour necrosis factor-induced antiphospholipid syndrome. Adalimumab was discontinued, and she was treated with the vitamin K antagonist warfarin and low-dose aspirin. Upon resolution of the antiphospholipid antibodies, she was transitioned to aspirin alone without recurrence of thrombosis.


Assuntos
Adalimumab/efeitos adversos , Anti-Inflamatórios/efeitos adversos , Síndrome Antifosfolipídica/induzido quimicamente , Mãos/irrigação sanguínea , Isquemia/induzido quimicamente , Doenças Vasculares Periféricas/induzido quimicamente , Aspirina/uso terapêutico , Doença de Crohn/tratamento farmacológico , Feminino , Humanos , Pessoa de Meia-Idade , Artéria Radial/diagnóstico por imagem , Artéria Radial/fisiopatologia , Varfarina/uso terapêutico
2.
Medicine (Baltimore) ; 98(13): e15052, 2019 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-30921233

RESUMO

RATIONALE: Aromatase inhibitors (AIs) are a class of drugs widely used in the treatment of estrogen sensitive breast and ovarian cancer which convert testosterone to estradiol and androstenedione to estrogen. The AIs of third generation, including anastrazole, letrozole and exemestane, have actually become the standard of care of estrogen-receptor-positive breast cancer in menopausal women and are recommended as adjuvant treatment after surgery in place of/or following tamoxifen. Their main side-effects include reduction in bone mineral density, occurrence of menopausal manifestations and development of musculoskeletal symptoms which are, usually, transient, but sometimes evolve into a typical form of arthritis, such as rheumatoid arthritis (RA). Recently, a pathogenic linkage with other autoimmunity diseases, such as Sjogren syndrome (SjS), anti-synthetase antibody syndrome (ASAS), systemic sclerosis (SS) and subacute cutaneous lupus erythematosus (SCLE), was also described. PATIENT CONCERNS: Here, we report the first case of a patient with primary antiphospholipid syndrome (APS) developed during treatment with anastrazole. DIAGNOSIS: The patient developed a sudden onset of speech disturbance and disorientation, due to ischemic lesions, after 6 months of AIs therapy and the laboratory examination showed the positivity of anti-Cardiolipin antibodies, anti-ß2 Glycoprotein 1 antibodies and Lupus Anticoagulant, so a certain diagnosis of APS was achieved. INTERVENTIONS: The patient was treated with warfarin associated to hydroxychloroquine and monthly cycles of low doses intravenous immunoglobulins. OUTCOMES: A good control of the disease was obtained despite the continuation of anastrazole; the patient's clinical and laboratory situation remained not modified after AIs withdrawal. LESSONS: We discussed the possible role of anastrazole treatment in inducing APS in our patient, reporting the available literature data about the association between AIs treatment and autoimmune diseases. Furthermore, we analyzed the mechanism of action of estrogens in the pathophysiology of autoimmune rheumatic disorders.


Assuntos
Anastrozol/efeitos adversos , Antineoplásicos Hormonais/efeitos adversos , Síndrome Antifosfolipídica/induzido quimicamente , Inibidores da Aromatase/efeitos adversos , Neoplasias da Mama/tratamento farmacológico , Feminino , Humanos , Pessoa de Meia-Idade
3.
Rheumatology (Oxford) ; 58(4): 645-649, 2019 04 01.
Artigo em Inglês | MEDLINE | ID: mdl-30521019

RESUMO

OBJECTIVE: Idiopathic osteonecrosis of the femoral head (ION) is a common complication of SLE associated with CS therapy. Although the pathogenesis of ION involves local bone ischaemia favoured by thrombophilia, the involvement of aPL in lupus ION remains to be elucidated. We have previously reported the aPL score (aPL-S) as a quantitative marker of aPL and the development of thrombotic events in autoimmune diseases. The aim of this study was to identify the impact of aPL on the development of ION using aPL-S. METHODS: This was a single-centre retrospective study comprising 88 consecutive SLE patients who underwent MRI of the hip joints from January 2000 to March 2017. Baseline characteristics, pharmacotherapy and total hip arthroplasty performed during follow-up were evaluated. RESULTS: The presence of ION was confirmed by MRI scan in 38 patients (43.1%). Male gender, positivity of any aPL, aPL-S, high aPL-S (≥30) and high dose of CS were identified as risk factors for ION by univariate analysis. Multivariate analysis revealed high aPL-S (odds ratio 5.12, 95% CI 1.18-29.79) and use of high-dose CS (odds ratio 10.25, 95% CI 3.00-48.38) as independent variables. Kaplan-Meier analysis showed that patients with high aPL-S received total hip arthroplasty more frequently than those without aPL (P = 0.010). CONCLUSIONS: We newly identified high aPL-S as an important risk factor for ION development in SLE, suggesting the involvement of aPL-induced coagulopathy in the pathophysiology of lupus ION.


Assuntos
Corticosteroides/efeitos adversos , Anticorpos Antifosfolipídeos/sangue , Síndrome Antifosfolipídica/complicações , Necrose da Cabeça do Fêmur/induzido quimicamente , Lúpus Eritematoso Sistêmico/tratamento farmacológico , Adulto , Síndrome Antifosfolipídica/induzido quimicamente , Síndrome Antifosfolipídica/imunologia , Biomarcadores , Feminino , Necrose da Cabeça do Fêmur/imunologia , Humanos , Modelos Logísticos , Lúpus Eritematoso Sistêmico/imunologia , Masculino , Pessoa de Meia-Idade , Razão de Chances , Estudos Retrospectivos , Fatores de Risco
4.
PLoS One ; 13(11): e0206814, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30399161

RESUMO

BACKGROUND: Antiphospholipid syndrome is associated with endothelial dysfunction, which leads to thrombosis and early atheroma. Given that hydroxychloroquine has anti-thrombotic properties in lupus, we hypothesized that it could reduce endothelial dysfunction in an animal model of antiphospholipid syndrome. We evaluated the effect of hydroxychloroquine in preventing endothelial dysfunction in a mouse model of antiphospholipid syndrome. METHODS: Antiphospholipid syndrome was induced by an injection of monoclonal anti-beta-2-GPI antibodies. Vascular reactivity was evaluated in mesenteric resistance arteries isolated from mice 3 weeks (APL3W) after receiving a single injection of anti-beta-2-GPI antibodies and after 3 weeks of daily oral hydroxychloroquine treatment (HCQ3W) compared to control mice (CT3W). We evaluated endothelial dysfunction by measuring acetylcholine-mediated vasodilation. A pharmacological approach was used to evaluate NO synthase uncoupling (tetrahydrobiopterin) and the generation of reactive oxygen species (Tempol). RESULTS: Impaired acetylcholine-mediated dilation was evidenced in mice 3 weeks after anti-beta-2-GPI antibodies injection compared to CT3W, by reduced maximal dilation (p<0.0001) and sensitivity (pKd) (p = 0.01) to acetylcholine. Hydroxychloroquine improved acetylcholine-dependent dilation, on pKd (p = 0.02) but not maximal capacity compared to untreated mice. The addition of tetrahydrobiopterin (p = 0.02) and/or Tempol (p = 0.0008) improved acetylcholine-mediated dilation in APL3W but not in HCQ3W. CONCLUSIONS: We demonstrated that endothelial dysfunction in mouse resistance arteries persisted at 3 weeks after a single injection of monoclonal anti-beta-2-GPI antibodies, and that hydroxychloroquine improved endothelium-dependent dilation at 3 weeks, through improvement of NO synthase coupling and oxidative stress reduction.


Assuntos
Síndrome Antifosfolipídica/tratamento farmacológico , Endotélio/efeitos dos fármacos , Hidroxicloroquina/administração & dosagem , Estresse Oxidativo/efeitos dos fármacos , Animais , Anticorpos Anti-Idiotípicos/administração & dosagem , Anticorpos Anti-Idiotípicos/toxicidade , Síndrome Antifosfolipídica/induzido quimicamente , Síndrome Antifosfolipídica/patologia , Modelos Animais de Doenças , Endotélio/patologia , Humanos , Artérias Mesentéricas/efeitos dos fármacos , Artérias Mesentéricas/patologia , Camundongos , Trombose/tratamento farmacológico , Trombose/imunologia , Trombose/patologia , Vasodilatação/efeitos dos fármacos , beta 2-Glicoproteína I/administração & dosagem , beta 2-Glicoproteína I/toxicidade
6.
Brain Struct Funct ; 223(7): 3463-3471, 2018 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-29936552

RESUMO

The antiphospholipid syndrome (APS) is an autoimmune disease characterized by the presence of antiphospholipid antibodies, which may trigger vascular thrombosis with consecutive infarcts. However, cognitive dysfunctions representing one of the most commonest neuropsychiatric symptoms are frequently present despite the absence of any ischemic brain lesions. Data on the structural and functional basis of the neuropsychiatric symptoms are sparse. To examine the effect of APS on hippocampal neurogenesis and on white matter, we induced experimental APS (eAPS) in adult female Balb/C mice by immunization with ß2-glycoprotein 1. To investigate cell proliferation in the dentate gyrus granular cell layer (DG GCL), eAPS and control mice (n = 5, each) were injected with 5-bromo-2'-deoxyuridine (BrdU) once a day for 10 subsequent days. Sixteen weeks after immunization, eAPS resulted in a significant reduction of BrdU-positive cells in the DG GCL compared to control animals. However, double staining with doublecortin and NeuN revealed a largely preserved neurogenesis. Ultrastructural analysis of corpus callosum (CC) axons in eAPS (n = 6) and control mice (n = 7) revealed no significant changes in CC axon diameter or g-ratio. In conclusion, decreased cellular proliferation in the hippocampus of eAPS mice indicates a limited regenerative potential and may represent one neuropathological substrate of cognitive changes in APS while evidence for alterations of white matter integrity is lacking.


Assuntos
Síndrome Antifosfolipídica/induzido quimicamente , Síndrome Antifosfolipídica/patologia , Proliferação de Células , Giro Denteado/patologia , Animais , Anticorpos Antifosfolipídeos/metabolismo , Autoantígenos/farmacologia , Escala de Avaliação Comportamental , Bromodesoxiuridina/administração & dosagem , Bromodesoxiuridina/metabolismo , Diferenciação Celular/fisiologia , Corpo Caloso/ultraestrutura , Modelos Animais de Doenças , Feminino , Fluorescência , Camundongos , Camundongos Endogâmicos BALB C , Neurogênese , Radiossensibilizantes/administração & dosagem , Radiossensibilizantes/metabolismo , beta 2-Glicoproteína I/farmacologia
8.
Lupus ; 27(2): 333-335, 2018 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-28592198

RESUMO

We report an original case of reversible antiphospholipid syndrome (APS) due to minocycline in a young male patient who experienced recurrent strokes while taking minocycline. He started minocycline therapy (50 mg twice daily) at 15 years old for acne. After three years of treatment, the patient experienced a lateral medullary syndrome. He was treated with aspirin while minocycline was continued. Eighteen months later, the patient complained about horizontal binocular diplopia. MRI revealed an infarct of the oculomotor nerve nucleus. Laboratory investigations revealed high titers of anti-beta 2 glycoprotein 1 (antiß2GP1) antibodies of 470 U/ml (normal range <15 U/ml) and antiphosphatidylethanolamine antibodies of 137.4 U/ml (normal range <18 U/ml). Other laboratory tests were normal. Six weeks after discontinuation of minocycline, anti-ß2GP1 antibodies decreased to 335 U/ml and to 36 U/ml at six months and then remained negative for six years. Many drugs have been considered as possibly causing APS but only in a limited number of patients. To our knowledge this is the first case of drug-induced APS with complete disappearance of high titers of anti-ß2GP1 antibodies after minocycline withdrawal. This case also illustrates the need to monitor the levels of antiphospholipid antibodies, even though initial values are high and confirmed after 12 weeks.


Assuntos
Anticorpos Antifosfolipídeos/imunologia , Síndrome Antifosfolipídica/induzido quimicamente , Minociclina/efeitos adversos , Acidente Vascular Cerebral/induzido quimicamente , beta 2-Glicoproteína I/antagonistas & inibidores , Antibacterianos/efeitos adversos , Humanos , Síndrome Medular Lateral/induzido quimicamente , Síndrome Medular Lateral/diagnóstico por imagem , Imagem por Ressonância Magnética , Masculino , Minociclina/administração & dosagem , Minociclina/uso terapêutico , Acidente Vascular Cerebral/etiologia , Resultado do Tratamento , Vasculite/induzido quimicamente , Vasculite/diagnóstico por imagem , Adulto Jovem , beta 2-Glicoproteína I/análise
9.
Pharmacol Res ; 120: 206-218, 2017 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-28366835

RESUMO

Direct-acting oral anticoagulants (DOACs) were claimed to cause a potential paradigm shift in the therapeutic scenario of patients requiring short- and long-term anticoagulation, by virtue of their pharmacological properties, perceived as innovative. The evidence gathered so far (from pre-approval pivotal trials to real-world post-marketing observational data) consistently confirmed that DOACs are overall comparable to vitamin-K antagonists (VKAs) in terms of safety, efficacy and effectiveness and unequivocally documented a consistent and clinically relevant reduced risk of intracranial bleeding in the settings of non-valvular atrial fibrillation (NVAF) and venous thromboembolism (VTE). Interestingly, two parallel paths can be identified in the current research scenario: A) in the aforementioned consolidated therapeutic indications, an innovative approach is directed towards tailored treatment strategies, to identify patients most likely to benefit from one of the different anticoagulant drugs, in particular subpopulations at increased risk of adverse events (e.g., bleeding); B) in unconventional settings, DOACs are gaining interest for potential use in emerging diseases characterized by arterial and venous thromboembolic risk. In these scenarios, the risk-benefit profile of DOACs, as compared to VKAs or heparins, is less defined. The aim of this review is to critically assess the body of evidence underlying emerging therapeutic uses of DOACs (e.g., heparin-induced thrombocytopenia, anti-phospholipid antibody syndrome), including evolving issues in special populations (e.g., patients with VTE and cancer or cirrhosis). This will be achieved by analyzing the strength (i.e., systematic reviews, randomized clinical trials, observational studies, case report/series) and consistency (i.e., concordance) of both published and unpublished evidence registered in major public repositories.


Assuntos
Anticoagulantes/uso terapêutico , Trombose/tratamento farmacológico , Animais , Anticoagulantes/administração & dosagem , Anticoagulantes/efeitos adversos , Síndrome Antifosfolipídica/induzido quimicamente , Prática Clínica Baseada em Evidências , Hemorragia/induzido quimicamente , Humanos , Neoplasias/complicações , Trombocitopenia/induzido quimicamente , Trombose/complicações
11.
Rheumatology (Oxford) ; 54(4): 722-7, 2015 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-25273993

RESUMO

OBJECTIVE: IgG aPL against domain I of ß2-glycoprotein I (ß2GPI) [anti-DI (aDI)] is associated with the pathogenesis of APS, an autoimmune disease defined by thrombosis and pregnancy morbidity. To date, however, no study has demonstrated direct pathogenicity of IgG aDI in vivo. In this proof-of-concept study, we designed a novel system to affinity purify polyclonal aDI aPL in order to assess its prothrombotic ability in a well-characterized mouse microcirculation model for APS. METHODS: Two polyclonal IgG fractions were isolated from serum of a patient with APS, both with high aPL activity but differing in aDI activity (aDI-rich and aDI-poor). These IgG fractions were tested for their pathogenic ability in an in vivo mouse model of thrombosis. Male CD1 mice were injected intraperitoneally with either aDI-rich or aDI-poor IgG; as a control, IgG isolated from healthy serum was used. A pinch injury was applied to the right femoral vein and thrombus dynamics and tissue factor activity in isolated tissue were evaluated. RESULTS: Both aDI-rich and aDI-poor IgG retained aCL and anti-ß2GPI activity, while only aDI-rich IgG displayed high aDI activity, as defined by our in-house cut-offs for positivity in each assay. aDI-rich IgG induced significantly larger thrombi in vivo compared with aDI-poor IgG (P < 0.0001). Similarly, aDI-rich IgG significantly enhanced the procoagulant activity of carotid artery endothelium and peritoneal macrophages isolated from experimental animals (P < 0.01). CONCLUSION: These data directly demonstrate that the ability to cause thrombosis in vivo is concentrated in the aDI fraction of aPL.


Assuntos
Anticorpos Antifosfolipídeos/farmacologia , Síndrome Antifosfolipídica/induzido quimicamente , Modelos Animais de Doenças , Imunoglobulina G/farmacologia , Camundongos , Trombose/induzido quimicamente , beta 2-Glicoproteína I/imunologia , Animais , Anticorpos Antifosfolipídeos/imunologia , Síndrome Antifosfolipídica/complicações , Síndrome Antifosfolipídica/imunologia , Imunoglobulina G/imunologia , Masculino , Estrutura Terciária de Proteína , Trombose/complicações , Trombose/imunologia
12.
Neuropathol Appl Neurobiol ; 41(5): 657-71, 2015 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-25201289

RESUMO

AIMS: The antiphospholipid syndrome (APS) is an autoimmune disease characterized by high titres of auto-antibodies (aPL) leading to thrombosis and consequent infarcts. However, many affected patients develop neurological symptoms in the absence of stroke. Similarly, in a mouse model of this disease (eAPS), animals consistently develop behavioural abnormalities despite lack of ischemic brain injury. Therefore, the present study was designed to identify structural alterations of hippocampal neurones underlying the neurological symptoms in eAPS. METHODS: Adult female Balb/C mice were subjected to either induction of eAPS by immunization with ß2-Glycoprotein 1 or to a control group. After sixteen weeks animals underwent behavioural and cognitive testing using Staircase test (experiment 1 and 2) and Y-maze alternation test (experiment 1) and were tested for serum aPL levels (both experiments). Animals of experiment 1 (n = 7/group) were used for hippocampal neurone analysis using Golgi-Cox staining. Animals of experiment 2 (n = 7/group) were used to analyse molecular markers of total dendritic integrity (MAP2), presynaptic plasticity (synaptobrevin 2/VAMP2) and dendritic spines (synaptopodin) using immunohistochemistry. RESULTS: eAPS mice developed increased aPL titres and presented with abnormal behaviour and impaired short term memory. Further, they revealed a reduction of dendritic complexity of hippocampal CA1 neurones as reflected by decreased dendritic length, arborization and spine density, respectively. Additional decrease of the spine-associated protein expression of Synaptopodin points to dendritic spines as major targets in the pathological process. CONCLUSION: Reduction of hippocampal dendritic complexity may represent the structural basis for the behavioural and cognitive abnormalities of eAPS mice.


Assuntos
Síndrome Antifosfolipídica/patologia , Região CA1 Hipocampal/patologia , Espinhas Dendríticas/patologia , Animais , Síndrome Antifosfolipídica/induzido quimicamente , Síndrome Antifosfolipídica/fisiopatologia , Autoanticorpos/sangue , Modelos Animais de Doenças , Feminino , Camundongos , Camundongos Endogâmicos BALB C , Microglia/patologia , Atividade Motora , beta 2-Glicoproteína I
13.
Autoimmunity ; 48(2): 87-99, 2015 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-25430703

RESUMO

Recent data concerning antiphospholipid syndrome (APS) induction have shown that ß2-glycoprotein I (ß2GPI) binds lipopolysaccharide (LPS), which results in conformational changes, exposition of a cryptic epitope and possible pathological anti-ß2GPI antibody production. In order to investigate the effects of LPS on the induction of APS-related pathology, we performed hyperimmunization of BALB/c and C57BL/6 mice with LPS, alone or in combination with tetanus toxoid (TTd), a protein structurally similar to ß2GPI. We report that, although high affinity pathological anti-ß2GPI antibodies were produced in all groups of animals, the reproductive pathology was recorded only in mice that received both LPS and TTd, implying on the important roles of both infections and molecular mimicry in APS pathogenesis. Moreover, APS-related reproductive pathology was more pronounced in BALB/c (lowered fertility and fecundity) than C57BL/6 mice (lowered fecundity), which correlated well with the disruption in natural antibody network observed in BALB/c mouse strain.


Assuntos
Síndrome Antifosfolipídica/patologia , Autoanticorpos/biossíntese , Infertilidade Feminina/patologia , Lipopolissacarídeos/administração & dosagem , Toxoide Tetânico/administração & dosagem , Animais , Síndrome Antifosfolipídica/induzido quimicamente , Síndrome Antifosfolipídica/complicações , Síndrome Antifosfolipídica/imunologia , Modelos Animais de Doenças , Sinergismo Farmacológico , Feminino , Imunização , Infertilidade Feminina/induzido quimicamente , Infertilidade Feminina/complicações , Infertilidade Feminina/imunologia , Tamanho da Ninhada de Vivíparos/efeitos dos fármacos , Tamanho da Ninhada de Vivíparos/imunologia , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Endogâmicos C57BL , Mimetismo Molecular , Gravidez , Especificidade da Espécie , beta 2-Glicoproteína I/química , beta 2-Glicoproteína I/imunologia
14.
J Autoimmun ; 55: 86-93, 2014 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-25150791

RESUMO

Mice immunized with ß2-glycoprotein I (ß2GPI) are an experimental model of the antiphospholipid syndrome (eAPS) displaying elevated titers of antiphospholipid antibodies (aPL). We presently studied whether the behavioral hyperactivity in eAPS mice is associated with in vivo binding and accumulation of IgG in the brain. At 6 weeks post immunization eAPS mice had significantly higher levels of aPL (1.32 ± 0.28 and 0.02 ± 0.01 AU, p < 0.001 by t-test) compared to adjuvant immunized controls, as measured by ELISA. Significant hyperactivity in a staircase test in the eAPS mice compared to controls was found in stair-climbing (18.4 ± 0.9 and 12.0 ± 1.7, respectively) and rearing measures (23.5 ± 2.1 and 12.5 ± 1.9, p < 0.01 by t-test). Immunofluorescence staining in eAPS mice revealed significant in vivo accumulation of IgG in cortical and hippocampal neurons which was not seen in controls. Staining for IgG was markedly intense in inhibitory interneurons co-stained for GAD67 in the hippocampus of eAPS mice. The integrity of the blood brain barrier (BBB) evaluated by injection of Evans blue (EB) was impaired in eAPS and adjuvant immunized mice compared to naïve mice. Electrophysiological recordings in hippocampal brain slices showed altered response to paired pulse stimulation as well as dysregulation of carbachol-induced γ- oscillations in eAPS mice compared to control. Penetration into the brain and direct interaction of aPL with inhibitory interneurons in the hippocampus may explain the hyperactive behavior of the eAPS mice. A direct role of aPL in causing CNS dysfunction points to these antibodies as an important therapeutic target in APS.


Assuntos
Anticorpos Antifosfolipídeos/imunologia , Síndrome Antifosfolipídica/imunologia , Hipocampo/imunologia , Imunoglobulina G/imunologia , Neurônios/imunologia , Animais , Síndrome Antifosfolipídica/induzido quimicamente , Síndrome Antifosfolipídica/patologia , Síndrome Antifosfolipídica/fisiopatologia , Modelos Animais de Doenças , Feminino , Glutamato Descarboxilase/imunologia , Hipocampo/patologia , Hipocampo/fisiopatologia , Camundongos , Camundongos Endogâmicos BALB C , Neurônios/patologia , beta 2-Glicoproteína I/toxicidade
15.
Clin Rheumatol ; 32(7): 1095-8, 2013 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-23559388

RESUMO

This study aims for the presentation of the first reported case of adalimumab-associated antiphospholipid syndrome (APS) and review of the literature on adalimumab-induced vasculitis and APS. A case of APS associated with adalimumab use in a 67-year-old woman is reported. The English medical literature was reviewed for antitumor necrosis factor (TNF) agents and their association with APS and vasculitis. Adalimumab is a fully humanized monoclonal antibody targeted against TNF alpha that is widely used in the treatment of rheumatoid arthritis, juvenile idiopathic arthritis, ankylosing spondylitis, psoriatic arthritis, psoriasis, and Crohn's disease. Literature review reveals several cases of anti-TNF-induced vasculitis including cases associated with adalimumab. We report the first case of adalimumab-induced APS in a 67-year-old woman who developed APS and vasculitis associated with de novo positive anti-cardiolipin (aCL) antibody following the third dose of adalimumab therapy for the treatment of spondyloarthropathy. This is the first case demonstrating that a short course of adalimumab therapy may induce immunoglobulin M aCL autoantibodies leading to APS. With the growing use of anti-TNF medications in immune-mediated and inflammatory diseases, adalimumab and other anti-TNF medications should be considered as a possible explanation for APS.


Assuntos
Anticorpos Monoclonais Humanizados/efeitos adversos , Anticorpos Monoclonais Humanizados/química , Síndrome Antifosfolipídica/induzido quimicamente , Adalimumab , Idoso , Anti-Inflamatórios/efeitos adversos , Anti-Inflamatórios/química , Anticorpos Anticardiolipina/sangue , Anticorpos Monoclonais/química , Anticorpos Monoclonais Humanizados/imunologia , Anticoagulantes/uso terapêutico , Evolução Fatal , Feminino , Humanos , Imunoglobulina M/sangue , Inflamação/diagnóstico , Espondiloartropatias/diagnóstico , Espondiloartropatias/tratamento farmacológico , Espondilite Anquilosante/tratamento farmacológico , Fator de Necrose Tumoral alfa/antagonistas & inibidores , Vasculite
16.
Immunol Res ; 56(1): 143-9, 2013 May.
Artigo em Inglês | MEDLINE | ID: mdl-23161337

RESUMO

One of the established animal models for autoimmune disease antiphospholipid syndrome (APS) is TTd hyperimmunization of mice. Tetanus toxoid (TTd) and plasma protein ß2GPI share structural homology so that immunization with TTd induces appearance of cross-reactive antibodies. In this paper, we have investigated the presence and dynamic of fluctuation of specific (anti-TTd) and auto (anti-ß2GPI) antibodies induced in BALB/c mice during secondary immune response after TTd immunization with alhydrogel or glycerol as adjuvants. In addition, we followed the induced reproductive pathology as a sign of autoimmune outcome. We show undoubtedly adjuvant dependance of (1) level of induced anti-TTd IgG antibodies, (2) changes in levels of low-affinity anti-ß2GPI IgG antibodies, and (3) change in fecundity and fertility during secondary immune response. These findings once more indicate the importance of chosen adjuvants used for successful immunization and eventual autoantibody outcome, this time associated with the processes involving low affinity, natural antibodies.


Assuntos
Adjuvantes Imunológicos/administração & dosagem , Hidróxido de Alumínio/administração & dosagem , Síndrome Antifosfolipídica/imunologia , Glicerol/administração & dosagem , Toxoide Tetânico/imunologia , Animais , Afinidade de Anticorpos/efeitos dos fármacos , Afinidade de Anticorpos/imunologia , Síndrome Antifosfolipídica/induzido quimicamente , Autoanticorpos/sangue , Reações Cruzadas , Modelos Animais de Doenças , Feminino , Fertilidade/efeitos dos fármacos , Fertilidade/imunologia , Humanos , Imunidade Humoral , Imunização Secundária , Camundongos , Camundongos Endogâmicos BALB C , Toxoide Tetânico/administração & dosagem , beta 2-Glicoproteína I/imunologia
17.
J Drugs Dermatol ; 11(9): 1117-8, 2012 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-23135659

RESUMO

Antiphospholipid antibody syndrome (APS) results from autoantibodies to cell surface phospholipids or phospholipid-binding proteins resulting in clotting anomalies and can have devastating sequelae, including stroke, deep venous thrombosis, pulmonary embolism, and recurrent spontaneous abortions. However, cutaneous manifestations are the first sign of APS in up to 41% of patients. We present a case report of APS that developed several days after taking trimethoprim/sulfamethoxazole. The clinical and pathological features of this unique presentation, differential diagnoses, and treatments are discussed.


Assuntos
Anti-Infecciosos/efeitos adversos , Síndrome Antifosfolipídica/induzido quimicamente , Combinação Trimetoprima e Sulfametoxazol/efeitos adversos , Síndrome Antifosfolipídica/complicações , Síndrome Antifosfolipídica/diagnóstico , Autoanticorpos/imunologia , Diagnóstico Diferencial , Feminino , Seguimentos , Humanos , Pessoa de Meia-Idade , Trombose/etiologia , Trombose/prevenção & controle
18.
Intern Med J ; 42(5): 585-91, 2012 May.
Artigo em Inglês | MEDLINE | ID: mdl-22616965

RESUMO

Catastrophic antiphospholipid antibody syndrome (CAPS) is a serious condition that is often unrecognised with a high mortality. Cessation of anticoagulation in antiphospholipid antibody syndrome (APS) can have devastating consequences with progression to CAPS. Making a diagnosis of APS can however be challenging because of the evolving diagnostic criteria and difficulty in confirming thromboses. Management of these patients can also be complex, especially in those with coexistent thrombocytopenia. New potential treatments are emerging targeted on the immunomodulation of APS rather than just prevention of thrombosis. This article aims to highlight these diagnostic and management difficulties by reporting and discussing three cases of APS with progression to CAPS following cessation of anticoagulation, one with fatal consequences, with confirmation of CAPS on autopsy, and two with successful treatment and outcomes.


Assuntos
Síndrome Antifosfolipídica/diagnóstico , Progressão da Doença , Fibrinolíticos/administração & dosagem , Suspensão de Tratamento , Adulto , Idoso , Síndrome Antifosfolipídica/induzido quimicamente , Síndrome Antifosfolipídica/tratamento farmacológico , Doença Catastrófica , Feminino , Fibrinolíticos/efeitos adversos , Humanos , Masculino
20.
Curr Rheumatol Rep ; 14(1): 71-8, 2012 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-22160568

RESUMO

Lupus anticoagulants (LA) are immunoglobulins (IgG, IgM, and/or IgA) which interfere with one or more of phospholipid-dependent in vitro coagulation tests, eg, activated partial thromboplastin time (aPTT), kaolin clotting time (KCT), dilute Russell viper venom time (dRVVT), and dilute prothrombin time (dPT). LAs may be seen in a variety of clinical settings including the primary antiphospholipid syndrome (APS), systemic lupus erythematosus (SLE), other autoimmune diseases, secondary to infections, malignancies, and in association with certain drugs. LAs associated with the antiphospholipid syndrome and other autoimmune disease recognize certain phospholipid-binding proteins (ß(2)-glycoprotein I [ß(2)GPI] or prothrombin). Many drugs have been implicated as possibly causing LAs, although the majority of such cases are limited to a select few. Drug-induced LAs are heterogeneous, differing in laboratory findings as well as related clinical complications. This paper reviews the English medical literature on drug-induced LA and potential mechanisms of induction.


Assuntos
Anticorpos Antifosfolipídeos/metabolismo , Síndrome Antifosfolipídica/induzido quimicamente , Inibidor de Coagulação do Lúpus/metabolismo , Lúpus Eritematoso Sistêmico/induzido quimicamente , Síndrome Antifosfolipídica/imunologia , Humanos , Lúpus Eritematoso Sistêmico/imunologia
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