RESUMO
A 73-year-old woman with multiple episodes of cerebral infarction was diagnosed with nonbacterial thrombotic endocarditis( NBTE) and antiphospholipid antibody syndrome. Transesophageal echocardiography revealed highly mobile tumors both in the mitral and the aortic valve, and the patient underwent aortic and mitral valve replacement. Pathologically, tumor of the mitral valve was a thrombus, and that of the aortic valve was a papillary fibroelastoma. Early after surgery, a recurrent thrombus was found in the left atrium, but no organ embolization ensued, and the patient had no adverse event for six months thereafter. Surgery is indicated only in limited cases of NBTE, because postoperative anticoagulation therapy is hard to manage and clinical outcome is poor.
Assuntos
Síndrome Antifosfolipídica , Endocardite , Trombose , Idoso , Anticoagulantes , Síndrome Antifosfolipídica/complicações , Síndrome Antifosfolipídica/patologia , Endocardite/complicações , Endocardite/diagnóstico por imagem , Endocardite/cirurgia , Feminino , Humanos , Valva Mitral/patologia , Trombose/diagnóstico por imagem , Trombose/etiologia , Trombose/cirurgiaRESUMO
ß2-glycoprotein I (ß2GPI) is an abundant multidomain plasma protein that plays various roles in the clotting and complement cascades. It is also the main target of antiphospholipid antibodies (aPL) in the acquired coagulopathy known as antiphospholipid syndrome (APS). Previous studies have shown that ß2GPI adopts two interconvertible biochemical conformations, oxidized and reduced, depending on the integrity of the disulfide bonds. However, the precise contribution of the disulfide bonds to ß2GPI structure and function is unknown. Here, we substituted cysteine residues with serine to investigate how the disulfide bonds C32-C60 in domain I (DI) and C288-C326 in domain V (DV) regulate ß2GPI's structure and function. Results of our biophysical and biochemical studies support the hypothesis that the C32-C60 disulfide bond plays a structural role, whereas the disulfide bond C288-C326 is allosteric. We demonstrate that absence of the C288-C326 bond, unlike absence of the C32-C60 bond, diminishes membrane binding without affecting the thermodynamic stability and overall structure of the protein, which remains elongated in solution. We also document that, while absence of the C32-C60 bond directly impairs recognition of ß2GPI by pathogenic anti-DI antibodies, absence of the C288-C326 disulfide bond is sufficient to abolish complex formation in the presence of anionic phospholipids. We conclude that the disulfide bond C288-C326 operates as a molecular switch capable of regulating ß2GPI's physiological functions in a redox-dependent manner. We propose that in APS patients with anti-DI antibodies, selective rupture of the C288-C326 disulfide bond may be a valid strategy to lower the pathogenic potential of aPL.
Assuntos
Anticorpos Antifosfolipídeos/imunologia , Síndrome Antifosfolipídica/imunologia , Autoanticorpos/imunologia , Proteínas Recombinantes/metabolismo , beta 2-Glicoproteína I/metabolismo , Regulação Alostérica , Anticorpos Antifosfolipídeos/sangue , Síndrome Antifosfolipídica/patologia , Autoanticorpos/sangue , Linhagem Celular , Cristalografia por Raios X/métodos , Humanos , Oxirredução , Domínios Proteicos , Proteínas Recombinantes/química , Proteínas Recombinantes/genética , Proteínas Recombinantes/isolamento & purificação , beta 2-Glicoproteína I/química , beta 2-Glicoproteína I/imunologia , beta 2-Glicoproteína I/isolamento & purificaçãoRESUMO
BACKGROUND: X-linked hyper-IgM syndrome (XHIGM) is a rare primary immunodeficiency caused by CD40 ligand defects. METHODS: We identified three patients with XHIGM in Ho Chi Minh City, Vietnam. Whole-exome sequencing, immunological analyses and western blot were performed to investigate phenotypic and genotypic features. RESULTS: Despite showing symptoms typical of XHIGM, including recurrent sinopulmonary infections, oral ulcers and otitis media, the diagnosis was significantly delayed. One patient developed anti-phospholipid syndrome, which has been documented for the first time in XHIGM syndrome. Two patients had elevated IgM levels and all of them had low IgG levels. Exome sequencing revealed mutations in the CD40LG gene: one novel splicing mutation c.156+2T>A and two previously characterised mutations (non-frameshift deletion c.436_438delTAC, stop-gain c.654C>A). Due to these mutations, the CD40 ligand was not expressed in any of the three patients, as demonstrated by western blot analysis. CONCLUSION: This is the first report of XHIGM syndrome in Vietnam indicates that an effective diagnostic strategy, such as sequencing analysis, contributes to reliable diagnosis and subsequent therapy.
Assuntos
Síndrome Antifosfolipídica/genética , Ligante de CD40/genética , Síndrome de Imunodeficiência com Hiper-IgM Tipo 1/genética , Fenótipo , Adolescente , Adulto , Síndrome Antifosfolipídica/etiologia , Síndrome Antifosfolipídica/patologia , Criança , Humanos , Síndrome de Imunodeficiência com Hiper-IgM Tipo 1/complicações , Síndrome de Imunodeficiência com Hiper-IgM Tipo 1/patologia , Masculino , MutaçãoRESUMO
Antiphospholipid syndrome (APS) is an autoimmune disease characterized by the production of ß2-glycoprotein I (ß2GPI)-dependent autoantibodies, with vascular thrombosis or obstetrical complications. Around 20% of APS patients are refractory to current treatments. Crassolide, a cembranoid diterpene extracted from soft corals, is a potential therapeutic candidate. Here, to examine the anti-inflammatory properties of crassolide, we first determined its effects on bone marrow-derived and splenic dendritic cells (DC). Specifically, we applied lipopolysaccharide (LPS) or ß2GPI stimulation and measured the expressions of CD80 and CD86, and secretions of cytokines. We also determined in the OT-II mice, if bone marrow-derived DC was able to stimulate antigen-specific T cells. Moreover, we examined the therapeutic potential of crassolide postimmunization in a murine model of APS that depended on active immunization with ß2GPI. The vascular manifestations were evaluated in terms of fluorescein-induced thrombi in mesenteric microvessels, whereas the obstetric manifestations were evaluated based on the proportion of fetal loss after pregnancy. We also measured blood titers of anti-ß2GPI antibody, splenic cell proliferative responses and cytokine secretions after ß2GPI stimulation ex vivo. Finally, we determined in these mice, hematological, hepatic and renal toxicities of crassolide. Crassolide after LPS stimulation suppressed DC maturation and secretion of tumor necrosis factor (TNF)-α, interleukin (IL)-6, IL-12 and IL-23, and downstream T cell activation. Crassolide could partially ameliorate both the vascular and obstetric manifestations of APS in BALB/c mice. Both blood titers of anti-ß2GPI antibody and splenic cell proliferation after ß2GPI stimulation were reduced. Splenic Th1 and Th17 responses were also lowered after ß2GPI stimulation. Finally, within therapeutic doses of crassolide, we found no evidence of its toxicity. In conclusion, we showed the ability of crassolide to suppress DC and downstream T cell responses. Crassolide is therefore a potential candidate for adjunctive therapy in APS.
Assuntos
Síndrome Antifosfolipídica/tratamento farmacológico , Células Dendríticas/efeitos dos fármacos , Diterpenos/farmacologia , Inflamação/tratamento farmacológico , Animais , Anti-Inflamatórios/química , Anti-Inflamatórios/farmacologia , Síndrome Antifosfolipídica/genética , Síndrome Antifosfolipídica/imunologia , Síndrome Antifosfolipídica/patologia , Antígeno B7-1/genética , Antígeno B7-2/genética , Células da Medula Óssea/efeitos dos fármacos , Células da Medula Óssea/imunologia , Células Dendríticas/imunologia , Células Dendríticas/patologia , Feminino , Regulação da Expressão Gênica/efeitos dos fármacos , Humanos , Inflamação/induzido quimicamente , Inflamação/genética , Inflamação/imunologia , Lipopolissacarídeos/toxicidade , Ativação Linfocitária/efeitos dos fármacos , Ativação Linfocitária/imunologia , Camundongos , Gravidez , beta 2-Glicoproteína I/toxicidadeRESUMO
Antiphospholipid syndrome (APS) is an acquired thrombophilic disorder in which autoantibodies are produced against a variety of phospholipids and phospholipid-binding proteins. The purpose of this article is to review cutaneous findings in patients with APS diagnosis. An overview regarding prevalence, description, pathogenesis and histopathology, are described for cutaneous manifestations of APS.
Assuntos
Anticorpos Antifosfolipídeos/imunologia , Síndrome Antifosfolipídica/patologia , Livedo Reticular/patologia , Dermatopatias/patologia , Vasculite/patologia , Adulto , Idoso , Anetodermia/etiologia , Anetodermia/patologia , Anticorpos Anticardiolipina/imunologia , Síndrome Antifosfolipídica/diagnóstico , Síndrome Antifosfolipídica/epidemiologia , Síndrome Antifosfolipídica/imunologia , Biópsia , Feminino , Gangrena/etiologia , Gangrena/patologia , Humanos , Livedo Reticular/diagnóstico , Livedo Reticular/etiologia , Livedo Reticular/imunologia , Inibidor de Coagulação do Lúpus/imunologia , Masculino , Papulose Atrófica Maligna/etiologia , Papulose Atrófica Maligna/patologia , Pessoa de Meia-Idade , Necrose/diagnóstico , Necrose/etiologia , Prevalência , Dermatopatias/imunologia , Úlcera/patologia , Vasculite/etiologiaRESUMO
Vascular occlusion has multiple, diverse clinical manifestations, some of which can have grave consequences for patients. It also has a wide variety of causes, including thrombi, which we recently addressed in partI of this review. In this second part, we look at additional causes of vascular occlusion.
Assuntos
Transtornos da Coagulação Sanguínea/complicações , Embolia/complicações , Dermatopatias Vasculares/etiologia , Anticoagulantes/efeitos adversos , Síndrome Antifosfolipídica/complicações , Síndrome Antifosfolipídica/patologia , Calciofilaxia/complicações , Calciofilaxia/patologia , Cocaína/efeitos adversos , Feminino , Corpos Estranhos/complicações , Corpos Estranhos/patologia , Humanos , Isquemia/etiologia , Isquemia/patologia , Levamisol/efeitos adversos , Livedo Reticular/etiologia , Livedo Reticular/patologia , Masculino , Papulose Atrófica Maligna/patologia , Necrose , Neoplasias/complicações , Neoplasias/patologia , Paraproteinemias/complicações , Paraproteinemias/patologia , Pele/irrigação sanguínea , Dermatopatias Vasculares/induzido quimicamente , Dermatopatias Vasculares/patologia , Úlcera Cutânea/etiologia , Úlcera Cutânea/patologia , Síndrome de Sneddon/patologiaRESUMO
Despite the widespread use of antiplatelets and anticoagulants, women with antiphospholipid syndrome (APS) may face pregnancy complications associated with placental dysplasia. Neutrophil extracellular traps (NETs) are involved in the pathogenesis of many autoimmune diseases, including vascular APS; however, their role in obstetric APS is unclear. Herein, we investigated the role of NETs by quantifying cell-free DNA and NET marker levels. Live-cell imaging was used to visualize NET formation, and MAPK signalling pathway proteins were analysed. Cell migration, invasion and tube formation assays were performed to observe the effects of NETs on trophoblasts and human umbilical vein endothelial cells (HUVECs). The concentrations of cell-free DNA and NETs in sera of pregnant patients with APS were elevated compared with that of healthy controls (HCs) matched to gestational week. APS neutrophils were predisposed to spontaneous NET release and IgG purified from the patients (APS-IgG) induced neutrophils from HCs to release NETs. Additionally, APS-IgG NET induction was abolished with inhibitors of reactive oxygen species, AKT, p38 MAPK and ERK1/2. Moreover, NETs were detrimental to trophoblasts and HUVECs. In summary, APS-IgG-induced NET formation deserves further investigation as a potential novel therapeutic target in obstetrical APS.
Assuntos
Anticorpos Antifosfolipídeos/efeitos adversos , Síndrome Antifosfolipídica/imunologia , Síndrome Antifosfolipídica/patologia , Armadilhas Extracelulares/metabolismo , Células Endoteliais da Veia Umbilical Humana/patologia , Trofoblastos/patologia , Adulto , Síndrome Antifosfolipídica/sangue , Movimento Celular/efeitos dos fármacos , Ácidos Nucleicos Livres/metabolismo , Inibidores Enzimáticos/farmacologia , Feminino , Humanos , Imunoglobulina G/sangue , Neovascularização Fisiológica/efeitos dos fármacos , Gravidez , Espécies Reativas de Oxigênio/metabolismo , Transdução de Sinais/efeitos dos fármacos , Adulto JovemRESUMO
BACKGROUND: Renal biopsy is the cornerstone of systemic lupus erythematosus (SLE) nephritis and antiphospholipid syndrome (APS) nephropathy management. However, transcutaneous renal biopsy (TCRB) is hampered by the antithrombotic treatment frequently prescribed for those diseases. Transjugular renal biopsy (TJRB) offers an attractive alternative for patients at increased risk of bleeding. The primary objective of the study was to describe the safety profile and diagnostic performance of TJRB in SLE and APS patients. METHODS: All SLE and/or APS patients who underwent a renal biopsy in our department (between January 2004 and October 2016) were retrospectively reviewed. Major complications were death, haemostasis nephrectomy, renal artery embolization, red blood cell transfusion, sepsis and vascular thrombosis; macroscopic haematuria, symptomatic perirenal/retroperitoneal bleeding and renal arteriovenous fistula without artery embolization were considered as minor complications. RESULTS: Two hundred and fifty-six TJRBs-119 without antithrombotics (untreated), 69 under aspirin and 68 on anticoagulants and 54 TCRBs without antithrombotics-were analysed. Their major and minor complication rates, respectively, did not differ significantly for the four groups: 0 and 8% for untreated TJRBs, 1 and 6% for aspirin-treated, 6 and 10% for anticoagulant-treated and 2 and 2% for TCRBs. The number of glomeruli sampled and the biopsy contribution to establishing a histological diagnosis was similar for the four groups. CONCLUSIONS: TJRBs obtained from SLE and APS patients taking antithrombotics had diagnostic yields and safety profiles similar to those of untreated TCRBs. Thus, TJRB should be considered for SLE and APS patients at risk of bleeding.
Assuntos
Síndrome Antifosfolipídica/patologia , Fibrinolíticos/uso terapêutico , Veias Jugulares/cirurgia , Lúpus Eritematoso Sistêmico/patologia , Nefrite Lúpica/tratamento farmacológico , Complicações Pós-Operatórias/prevenção & controle , Adulto , Síndrome Antifosfolipídica/tratamento farmacológico , Síndrome Antifosfolipídica/cirurgia , Biópsia , Feminino , Humanos , Lúpus Eritematoso Sistêmico/tratamento farmacológico , Lúpus Eritematoso Sistêmico/cirurgia , Nefrite Lúpica/patologia , Nefrite Lúpica/cirurgia , Masculino , Prognóstico , Estudos RetrospectivosRESUMO
Abstract Background: Hemorrhoid disease (HD) is one of the most common gastrointestinal complaints worldwide, affecting 4.4% of the general population in the United States. Since antiphospholipid syndrome (APS) may lead to intra-abdominal thrombosis, one may expect that this condition can impact the risk for HD development. Additionally, as APS patients are more prone to thrombosis and treatment with anticoagulants may increase risk of bleeding, one may also infer that rates of HD complications may be higher in this scenario. Nevertheless, no data in these regards have been published until now. The objective of the present study is to evaluate frequency of HD and describe its complications rates in antiphospholipid syndrome APS patients. Methods: We consecutively invited patients who fulfilled APS criteria to undergo proctological examination. After examination, patients were divided in two groups, based on the presence of HD, and compared regarding different clinical manifestations and antiphospholipid profile. We performed the analysis of the data, using chi-square and Mann Whitney U when applicable and considering a significance level of 0.05. Multivariate regression analysis included age and variables with p < 0.10 in the bivariate analysis. Results: Forty-one APS patients agreed to undergo proctological examination. All were female and overall median age was 43 (36-49). Seventeen (41.4%) patients were diagnosed with HD, with the following frequency distribution: 7 internal (41.2%), 4 external (23.5%) and 5 mixed hemorrhoids (29.4%). Of the internal hemorrhoids, 5 patients were classified as grade I (71.4%), 1 grade II (14.3%), and 1 grade IV (14.3%). Prior gestation ( p = 0.067) and constipation ( p = 0.067) correlated with a higher frequency of HD. In multivariate analysis, constipation remained as an important risk factor (OR 3.92,CI95% 1.03-14.2, p = 0.037). Five out of 17 patients (29.4%) reported anal bleeding, but it did not correlate with warfarin dose ( p = 0.949). Surgical treatment was indicated for 10 patients (58.8%). Other anorectal findings were anal fissure, plicoma, condyloma and one chlamydial retitis. Conclusion: We found an unexpected high frequency of hemorrhoids in APS patients, with a great proportion requiring surgical treatment.(AU)
Assuntos
Humanos , Doenças Retais/diagnóstico , Síndrome Antifosfolipídica/patologia , Anticorpos Antifosfolipídeos/sangue , Estudos Transversais , ColonoscopiaAssuntos
Síndrome Antifosfolipídica/terapia , Transplante de Células-Tronco Hematopoéticas/métodos , Técnicas de Imunoadsorção , Adulto , Anticorpos Antifosfolipídeos/sangue , Anticorpos Antifosfolipídeos/isolamento & purificação , Síndrome Antifosfolipídica/imunologia , Síndrome Antifosfolipídica/patologia , Ciclofosfamida/uso terapêutico , Hemorragia/diagnóstico por imagem , Hemorragia/terapia , Humanos , Pessoa de Meia-Idade , Alvéolos Pulmonares/diagnóstico por imagem , Alvéolos Pulmonares/patologia , Rituximab/uso terapêutico , Tomografia Computadorizada por Raios X , Transplante AutólogoRESUMO
Type I Interferon gene expression has been shown to play an important role in the pathogenesis of several systemic autoimmune disorders, paving the way for its potential use as a surrogate marker or a therapeutic tool. While the concept of type I interferon signature and its correlation with clinical phenotypes and disease activity, along with anti-interferon targeted therapy have been vastly investigated in patients with systemic lupus erythematosus, there is a paucity of data concerning antiphospholipid syndrome patients. In this review, we summarize the current knowledge on the pathogenetic and clinical implications of type I interferon expression in antiphospholipid syndrome and discuss the therapeutic possibility of targeting molecules along the interferon signaling pathway. A number of recent studies have shown a type I interferon gene expression induction in patients with primary antiphospholipid syndrome via the plasmacytoid dendritic cell pathway, toll like receptors (TLRs) such as TLR7 and TLR9, anti-beta2glycoprotein I antibody-mediated neutrophil activation and neutrophil extracellular traps (NETs) release in a TLR4-dependent fashion, and a subsequent B cell and plasmablast activation. An association between type I interferon expression and several demographic, clinical and laboratory characteristics including age, gender, pregnancy complications such as eclampsia, anti-beta2glycoprotein I antibodies, and a negative correlation with hydroxychloroquine and/or statin use, has been shown. Correlation of high interferon scores to worse outcomes in prospective studies could direct the initiation for a prompt treatment in high-risk populations. Potential therapeutic approaches targeting type I interferon production and signaling pathway components might include anti-interferon or interferon receptor monoclonal antibodies, or an interferon based therapeutic vaccine as was indicated from previous systemic lupus erythematosus studies, TLR inhibitors including hydroxychloroquine and anti-TLR antibodies, plasmacytoid dendritic cell inhibition, adenosine-receptor agonists, and plasmablast targeting treatments. Well-designed studies are needed to further assess the immunomodulatory potential of the above targets for therapeutic intervention in patients with primary antiphospholipid syndrome.
Assuntos
Síndrome Antifosfolipídica , Regulação da Expressão Gênica/imunologia , Interferon Tipo I/imunologia , Lúpus Eritematoso Sistêmico , Síndrome Antifosfolipídica/imunologia , Síndrome Antifosfolipídica/patologia , Síndrome Antifosfolipídica/terapia , Lúpus Eritematoso Sistêmico/imunologia , Lúpus Eritematoso Sistêmico/terapiaRESUMO
Anti-phospholipid syndrome (APS) is characterized by recurrent pathological pregnancy, arterial or venous thrombosis in the presence of anti-phospholipid antibody (aPL). Complement activation is recognized as an intermediate link leading to placental thrombosis and placental inflammation in APS model mice. Decay accelerating factor (DAF, CD55), MAC-inhibitory protein (MAC-IP, CD59) and membrane co-factor protein (MCP, CD46) are important complement inhibitory proteins (CIPs) highly expressed in normal placenta to curb excessive complement activation and its mediated injuries. Anti-ß2 glycoprotein I (anti-ß2GPI) antibody is an important aPL. We found that placental DAF and CD46 decreased in ß2GPI passively immunized APS model mice, accompanied by C3 deposition, neutrophil infiltration and increased proinflammatory cytokine levels detected in its placenta. Progesterone supplement can up-regulate DAF but not CD46 expression, curb C3 activation and decrease proinflammatory cytokines levels to reduce fetal loss frequency. Progesterone receptor antagonist (mifepristone) or knock-down DAF with specific siRNA, above the protective effects of progesterone, were significantly weakened. Another sex hormone, oestrogen, has no significant effect on placental DAF and C3 contents and fetal loss frequency in the APS mice model. This may be an important mechanism by which progesterone induces maternal-fetal immune tolerance. At the same time, it may provide evidence for the use of progesterone in APS abortion patients.
Assuntos
Síndrome Antifosfolipídica/imunologia , Antígenos CD55/imunologia , Placenta/imunologia , Placenta/lesões , Complicações na Gravidez/imunologia , Progesterona/farmacologia , Regulação para Cima/efeitos dos fármacos , Animais , Síndrome Antifosfolipídica/patologia , Feminino , Camundongos , Camundongos Endogâmicos BALB C , Placenta/patologia , Gravidez , Complicações na Gravidez/tratamento farmacológico , Complicações na Gravidez/patologia , Regulação para Cima/imunologiaRESUMO
Potentiation of neutrophil extracellular trap (NET) release is one mechanism by which antiphospholipid antibodies (aPL Abs) effect thrombotic events in patients with antiphospholipid syndrome (APS). Surface adenosine receptors trigger cyclic AMP (cAMP) formation in neutrophils, and this mechanism has been proposed to regulate NETosis in some contexts. Here we report that selective agonism of the adenosine A2A receptor (CGS21680) suppresses aPL Ab-mediated NETosis in protein kinase A-dependent fashion. CGS21680 also reduces thrombosis in the inferior vena cavae of both control mice and mice administered aPL Abs. The antithrombotic medication dipyridamole is known to potentiate adenosine signaling by increasing extracellular concentrations of adenosine and interfering with the breakdown of cAMP. Like CGS21680, dipyridamole suppresses aPL Ab-mediated NETosis via the adenosine A2A receptor and mitigates venous thrombosis in mice. In summary, these data suggest an anti-inflammatory therapeutic paradigm in APS, which may extend to thrombotic disease in the general population.
Assuntos
Agonistas do Receptor A2 de Adenosina/farmacologia , Adenosina/análogos & derivados , Síndrome Antifosfolipídica/tratamento farmacológico , Armadilhas Extracelulares/efeitos dos fármacos , Neutrófilos/efeitos dos fármacos , Fenetilaminas/farmacologia , Trombose Venosa/tratamento farmacológico , Adenosina/imunologia , Adenosina/metabolismo , Adenosina/farmacologia , Animais , Anticorpos Antifosfolipídeos/sangue , Síndrome Antifosfolipídica/genética , Síndrome Antifosfolipídica/imunologia , Síndrome Antifosfolipídica/patologia , AMP Cíclico/imunologia , AMP Cíclico/metabolismo , Dipiridamol/farmacologia , Modelos Animais de Doenças , Armadilhas Extracelulares/imunologia , Armadilhas Extracelulares/metabolismo , Fibrinolíticos/farmacologia , Regulação da Expressão Gênica , Humanos , Imunoglobulina G/sangue , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Neutrófilos/imunologia , Receptor A2A de Adenosina/genética , Receptor A2A de Adenosina/imunologia , Transdução de Sinais , Veia Cava Inferior/efeitos dos fármacos , Veia Cava Inferior/imunologia , Veia Cava Inferior/metabolismo , Trombose Venosa/genética , Trombose Venosa/imunologia , Trombose Venosa/patologiaRESUMO
AIM: Dysregulated apoptosis has been implicated in autoimmune diseases. In the present study, we investigated the apoptosis-related cytokines and apoptosis in patients with primary antiphospholipid syndrome (pAPS). METHOD: We prospectively recruited 12 pAPS patients, 17 antiphospholipid antibody (APA)-positive systemic lupus erythematosus (SLE) patients without APS manifestations (APA+ SLE), 13 SLE patients with secondary APS (APS+ SLE) and 10 healthy controls (HCs). Plasma levels of soluble apoptosis-inducing ligands and cytokines, and the expression levels of apoptosis-inducing ligands in peripheral blood mononuclear cells, were determined. In addition, blood lymphocytes/monocytes apoptosis were determined in six pAPS patients and six HCs, using flow cytometric analysis of caspase 3, 8 and 9 activities. RESULTS: There was a trend toward higher plasma levels of soluble tumor necrosis factor (TNF)-related apoptosis-inducing ligand (sTRAIL), interleukin-10 (IL-10) and TNF-α in pAPS patients when compared with HCs. We also observed higher plasma levels of IL-10 and TNF α in APA+ SLE and APS+ SLE patients when compared with HCs. However, there was no significant difference in blood lymphocytes/monocytes apoptosis between pAPS patients and HCs. CONCLUSION: There was a trend toward elevated plasma levels of sTRAIL, IL-10 and TNF-α, but no evidence for dysregulated apoptosis in pAPS patients.
Assuntos
Síndrome Antifosfolipídica/patologia , Proteínas Reguladoras de Apoptose/sangue , Apoptose , Citocinas/sangue , Linfócitos/patologia , Monócitos/patologia , Adulto , Síndrome Antifosfolipídica/sangue , Síndrome Antifosfolipídica/genética , Síndrome Antifosfolipídica/imunologia , Proteínas Reguladoras de Apoptose/genética , Biomarcadores/sangue , Estudos de Casos e Controles , Feminino , Humanos , Interleucina-10/sangue , Linfócitos/imunologia , Linfócitos/metabolismo , Masculino , Pessoa de Meia-Idade , Monócitos/imunologia , Monócitos/metabolismo , Estudos Prospectivos , Ligante Indutor de Apoptose Relacionado a TNF/sangue , Fator de Necrose Tumoral alfa/sangueAssuntos
Síndrome Antifosfolipídica/imunologia , Dor/imunologia , Doenças do Sistema Nervoso Periférico/imunologia , Fosfatidilserinas/imunologia , Protrombina/imunologia , Vasculite/imunologia , Síndrome Antifosfolipídica/complicações , Síndrome Antifosfolipídica/patologia , Síndrome Antifosfolipídica/terapia , Autoanticorpos/imunologia , Feminino , Glucocorticoides/uso terapêutico , Humanos , Imunoglobulina M/imunologia , Imunoglobulinas Intravenosas/uso terapêutico , Fatores Imunológicos/uso terapêutico , Pessoa de Meia-Idade , Condução Nervosa , Dor/complicações , Dor/patologia , Doenças do Sistema Nervoso Periférico/complicações , Doenças do Sistema Nervoso Periférico/patologia , Doenças do Sistema Nervoso Periférico/terapia , Vasculite/complicações , Vasculite/patologia , Vasculite/terapiaRESUMO
Lucio phenomenon is an atypical reaction of leprosy, characterized by vasculitic lesions that can mimic antiphospholipid syndrome (APS) clinically. Distinguishing the two can be difficult as antiphospholipid autoantibodies may be present in patients with leprosy. We report on a 32-year-old female patient presenting with a sudden onset of fever, hemorrhagic bullae, and skin necrosis on her lower legs. She was treated for APS due to the presence of antiphospholipid antibodies but had an inadequate response. A skin biopsy revealed thrombotic vasculopathy and necrotizing vasculitis associated with aggregation of foam cells in the perivascular area and subcutis, with acid-fast bacilli in the histiocytes and blood vessel walls. Direct immunofluorescence showed IgM, C3, and fibrinogen deposition in the superficial and deep dermal blood vessels. The pathology confirmed the diagnosis of Lucio phenomenon, and appropriate therapy was given. It is essential to evaluate the patient comprehensively, including clinical, serological, and pathological aspects, to obtain the correct diagnosis.
Assuntos
Anticorpos Antifosfolipídeos/metabolismo , Síndrome Antifosfolipídica , Hanseníase , Dermatopatias/metabolismo , Pele , Adulto , Síndrome Antifosfolipídica/metabolismo , Síndrome Antifosfolipídica/patologia , Feminino , Humanos , Hanseníase/metabolismo , Hanseníase/patologia , Pele/metabolismo , Pele/patologia , Dermatopatias/patologia , Vasculite/metabolismo , Vasculite/patologiaRESUMO
Thrombotic microangiopathy (TMA) develops from various etiologies, and it is often difficult to distinguish the etiology of TMA in kidney transplantation. Antiphospholipid syndrome (APS) is one of the differential diagnoses for TMA that may cause acute loss of graft function or fatal thrombotic complications. This report details a 66-year-old male patient with polycythemia after ABO-incompatible kidney transplantation. Antibody screening tests were negative before transplant. Despite administration of an adequate desensitization therapy including plasmapheresis and rituximab, he developed acute graft dysfunction on postoperative day 112 and graft biopsy revealed prominent microvascular inflammation in the glomerular capillaries without immunoglobulin deposits. Flow cytometric panel-reactive antibody screening failed to detect donor-specific antibodies at both pre-transplant and episode biopsies. Anticardiolipin antibody was repeatedly positive, but neither thrombosis nor previous thrombotic episodes were detected. After excluding several differential diagnoses, the graft dysfunction with unexplained TMA was treated with steroid pulse, plasmapheresis and rituximab re-induction. Anticardiolipin antibody disappeared after this intensive treatment and graft function recovered gradually and stabilized for 52 months. This report suggests that asymptomatic anticardiolipin antibody may be associated with acute graft dysfunction. Even if thrombotic episodes are not observed, an exist of anticardiolipin antibody may be one of the risk factors of renal TMA after kidney transplantation.