RESUMO
BACKGROUND: SerpinF2, SerpinG1, CystatinC and CD14 are involved in inflammatory processes and plasma extracellular vesicle (EV) -levels of these proteins have been reported to be associated with systemic vascular events. Evidence is accumulating that inflammatory processes may play a pivotal role both in systemic vascular events and in heart failure. Therefore, we studied the association between plasma extracellular vesicle SerpinF2-, SerpinG1-, CystatinC and CD14-levels and the occurrence of acute heart failure in patients. METHODS AND RESULT: Extracellular vesicle protein levels of SerpinG1, SerpinF2, CystatinC and CD14 were measured in an observational study of 404 subjects presenting with dysponea at the emergency department (4B-cohort). Plasma extracellular vesicles were precipitated in a total extracellular vesicles (TEX)-fraction and in separate LDL- and HDL-subfractions. Extracellular vesicle protein levels were measured with a quantitative immune assay in all 3 precipitates. Out of 404 subjects, 141 (35%) were diagnosed with acutely decompensated heart failure. After correction for confounders (including comorbidities and medications), levels of CD14 in the HDL-fraction (OR 1.53, p = 0.01), SerpinF2 in the TEX-and LDL-fraction (ORs respectively 0.71 and 0.65, p<0.05) and SerpinG1 in the TEX-fraction (OR 1.55, p = 0.004) were statistically significantly related to heart failure. Furthermore, extracellular vesicle CD14- and SerpinF2-levels were significantly higher in heart failure patients with preserved ejection fraction than in those with reduced ejection fraction. CONCLUSION: Extracellular vesicle levels of CD14, SerpinG1 and SerpinF2 are associated with the occurrence of heart failure in subjects suspected for acute heart failure, suggesting common underlying pathophysiological mechanisms for heart failure and vascular events.
Assuntos
Proteínas Inativadoras do Complemento 1/análise , Cistatina C/sangue , Vesículas Extracelulares/patologia , Insuficiência Cardíaca/sangue , Receptores de Lipopolissacarídeos/sangue , alfa 2-Antiplasmina/análise , Doença Aguda , Adulto , Idoso , Proteína Inibidora do Complemento C1 , Estudos Transversais , Cistatina C/análise , Feminino , Insuficiência Cardíaca/patologia , Humanos , Receptores de Lipopolissacarídeos/análise , Masculino , Pessoa de Meia-IdadeRESUMO
Introducción. El angioedema hereditario es una inmunodeficiencia primaria de carácter autosómico dominante, debida a un déficit en la proteína inhibidora del factor C1 y caracterizada por episodios recurrentes de edema subcutáneo y de las mucosas. Las impredecibles y frecuentes crisis de angioedema afectan la calidad de vida de los individuos que las padecen. Objetivo. Analizar las características clínicas de una familia con un caso índice de angioedema hereditario y determinar el impacto de la enfermedad en la calidad de vida. Materiales y métodos. En el estudio se incluyeron 26 miembros de la familia, a 25 de los cuales se les midieron los niveles sanguíneos del factor C4 del complemento y del inhibidor de C1 antigénico y funcional. Se utilizaron dos instrumentos, el SF-36 para evaluar la salud del adulto y el KIDSCREEN-27 para la calidad de vida de niños y adolescentes. Resultados. El 83 % de los individuos que reportaron síntomas cumplían con los criterios serológicos del angioedema hereditario de tipo I: valores bajos del factor C4 del complemento y del inhibidor de C1 cuantitativo (antigénico) y cualitativo (funcional). Se encontró que la calidad de vida en cuanto al bienestar psicológico y el desempeño emocional de los pacientes, se veía considerablemente afectada por los síntomas de la enfermedad. Conclusión. Este estudio provee información sobre la primera familia caracterizada con angioedema hereditario de tipo 1 en el Valle de Aburrá, Colombia. Aunque para ello se usó un instrumento genérico, se confirmó, además, el efecto negativo de la enfermedad en la calidad de vida de los individuos que la padecen.
Introduction: Hereditary angioedema is an autosomal dominant primary immunodeficiency caused by a deficiency of the C1 inhibitor protein and characterized by recurrent episodes of subcutaneous and mucosal edema. Unpredictable and frequent crisis of angioedema affect the quality of life of individuals suffering this kind of disorder. Objective: To analyze the clinical characteristics of a family with an index case of hereditary angioedema and to determine the impact of this disease on their quality of life. Materials and methods: Twenty six members of the family were included in the trial; 25 of them were analyzed for C4 complement and antigenic and functional C1 inhibitor blood levels. Two instruments (SF-365 and KIDSCREEN-27) were used to evaluate adult health quality and children and teenagers quality of life, respectively. Results: Eighty three percent (83%) of individuals reporting symptoms of the condition exhibited serological criteria of hereditary angioedema type I: low levels of both C4 complement and quantitative (antigenic) and qualitative (functional) C1 inhibitor. In relation to patients' psychological and emotional performance, their quality of life was significantly affected by the symptoms of hereditary angioedema. Conclusion: This study provides evidence of the first family in Valle de Aburrá (Colombia) characterized as having hereditary angioedema type I. Despite the use of a generic instrument, the negative impact on the quality of life of individuals suffering this disease was also confirmed.
Assuntos
Adolescente , Adulto , Idoso , Criança , Pré-Escolar , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Adulto Jovem , Angioedema Hereditário Tipos I e II/epidemiologia , Linhagem , Qualidade de Vida , Complemento C4/análise , Proteínas Inativadoras do Complemento 1/análise , Saúde da Família , Estudos Prospectivos , Colômbia/epidemiologia , Emoções , Proteína Inibidora do Complemento C1 , Angioedema Hereditário Tipos I e II/genética , Angioedema Hereditário Tipos I e II/imunologia , Angioedema Hereditário Tipos I e II/psicologia , Avaliação de SintomasAssuntos
Angioedema/diagnóstico , Diarreia/diagnóstico , Hidratação , Leucemia Linfocítica Crônica de Células B/complicações , Angioedema/tratamento farmacológico , Angioedema/etiologia , Anticorpos Monoclonais Murinos/administração & dosagem , Anticorpos Monoclonais Murinos/uso terapêutico , Proteínas Inativadoras do Complemento 1/análise , Proteína Inibidora do Complemento C1 , Complemento C1q/análise , Diagnóstico Diferencial , Diarreia/tratamento farmacológico , Diarreia/etiologia , Feminino , Humanos , Leucemia Linfocítica Crônica de Células B/tratamento farmacológico , Pessoa de Meia-Idade , Rituximab , Resultado do TratamentoRESUMO
UNLABELLED: Clinical studies as well as animal models emphasized the importance of the complement system in the pathogenesis of coronary atherosclerosis and cardiovascular diseases. Our aim was to examine the extent and clinical implication of complement system activation in patients with stable atherosclerotic coronary heart disease (ACHD). Seventy-six patients with stable angina pectoris (SAP) scheduled for elective coronary angiography were enrolled into the study. Percutaneous coronary intervention (PCI) was performed in 24 patients, in 27 patients (NOPCI group) the coronary angiography showed significant stenosis and bypass surgery (CABG) or optimal medical therapy (OMT) were advised, whereas in 25 patients the coronary angiography was negative (NC group). 115 volunteers served as healthy controls (HC). In all individuals, the plasma level of several complement activation products - C1rC1sC1inh, C3bBbP and SC5b-9 - were determined on admission, strictly before the coronary angiography. In patients with angiographically proven ACHD (PCI and NOPCI groups), the baseline C1rC1sC1inh levels were significantly higher compared to NC group and HC (p<0.0001, for both comparisons). According to the multiple logistic regression analysis, high C1rC1sC1inh level proved to be an independent biomarker of coronary heart disease (p<0.026, OR: 65.3, CI: 1.628-2616.284). CONCLUSION: Activation of the classical complement pathway can be observed in angiographically proven coronary atherosclerosis. Elevated C1rC1sC1inh levels might represent an useful biomarker for coronary artery disease.
Assuntos
Aterosclerose/diagnóstico , Proteínas Inativadoras do Complemento 1/análise , Complemento C1/análise , Doença da Artéria Coronariana/diagnóstico , Idoso , Aterosclerose/sangue , Estudos de Casos e Controles , Estudos de Coortes , Ativação do Complemento/fisiologia , Complemento C1/metabolismo , Proteínas Inativadoras do Complemento 1/metabolismo , Complemento C1r/análise , Complemento C1r/metabolismo , Complemento C1s/análise , Complemento C1s/metabolismo , Doença da Artéria Coronariana/sangue , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , PrognósticoRESUMO
Hereditary angioneurotic laryngeal edema (HALE) is an autosomal dominant hereditary disease in which there is a decrease or defect in the C1 inhibitor (C1-INH). The pathophysiology of HALE is characterized by recurrent spontaneous episodes of transient edema of the laryngeal mucose and submucosal tissue with remission at irregular. Patients may die because of a life-threatening acute upper airway obstruction caused by laryngeal edema. HALE was diagnosed on the clinical symptoms, family history, and markedly decreased serum C1-INH activity and C1-INH protein.
Assuntos
Angioedemas Hereditários/diagnóstico , Edema Laríngeo/diagnóstico , Proteínas Inativadoras do Complemento 1/análise , Proteínas Inativadoras do Complemento 1/metabolismo , Proteína Inibidora do Complemento C1 , Humanos , RecidivaRESUMO
Hereditary angioedema is characterized by sudden episodes of nonpitting edema that cause discomfort and pain. Typically the extremities, genitalia, trunk, gastrointestinal tract, face, and larynx are affected by attacks of swelling. Laryngeal swelling carries significant risk for asphyxiation. The disease results from mutations in the C1 esterase inhibitor gene that cause C1 esterase inhibitor deficiency. Attacks of hereditary angioedema result from contact, complement, and fibrinolytic plasma cascade activation, where C1 esterase inhibitor irreversibly binds substrates. Patients with hereditary angioedema cannot replenish C1 esterase inhibitor levels on pace with its binding. When C1 esterase inhibitor is depleted in these patients, vasoactive plasma cascade products cause swelling attacks. Trauma is a known trigger for hereditary angioedema attacks, and patients have been denied surgical procedures because of this risk. However, uncomplicated surgeries have been reported. Appropriate prophylaxis can reduce peri-operative morbidity in these patients, despite proteolytic cascade and complement activation during surgical trauma. We report a case of successful short-term prophylaxis with C1 esterase inhibitor in a 51-year-old man with hereditary angioedema who underwent redo mitral valve reconstructive surgery.
Assuntos
Angioedemas Hereditários/complicações , Proteínas Inativadoras do Complemento 1/administração & dosagem , Edema/prevenção & controle , Insuficiência da Valva Mitral/cirurgia , Valva Mitral/cirurgia , Complicações Pós-Operatórias/prevenção & controle , Anuloplastia da Valva Cardíaca , Proteínas Inativadoras do Complemento 1/análise , Proteína Inibidora do Complemento C1 , Edema/etiologia , Humanos , Masculino , Pessoa de Meia-Idade , Insuficiência da Valva Mitral/complicações , ReoperaçãoAssuntos
Anafilaxia/induzido quimicamente , Anticoagulantes/farmacologia , Coagulação Sanguínea/efeitos dos fármacos , Sulfatos de Condroitina/efeitos adversos , Contaminação de Medicamentos , Heparina/farmacologia , Trombocitopenia/induzido quimicamente , Anafilaxia/sangue , Anticoagulantes/análise , Anticoagulantes/uso terapêutico , Sulfatos de Condroitina/análise , Sulfatos de Condroitina/farmacologia , Proteínas Inativadoras do Complemento 1/análise , Proteína Inibidora do Complemento C1 , Convalescença , Ativação Enzimática/efeitos dos fármacos , Heparina/análise , Heparina/uso terapêutico , Humanos , Calicreínas/fisiologia , Cininogênios/sangue , Ativação Plaquetária/efeitos dos fármacos , Pré-Calicreína/análise , Pré-Calicreína/efeitos dos fármacos , Pré-Calicreína/metabolismo , Protrombina/metabolismo , Diálise Renal , Trombina/biossínteseRESUMO
BACKGROUND: Hereditary angio-oedema (HAE) has been associated with C1inhibitor deficiency. The first cases of type III HAE were described in patients with normal C1Inh antigenic protein level and function and normal C4 levels in 2000. This finding has been reported mostly in women with a family history and may be influenced by exogenous oestrogen exposure. OBJECTIVES: The purpose of this article is to describe the clinical, biological and genetic characteristics of a French population suffering from type III HAE. PATIENTS AND METHODS: We conducted a retrospective analysis of angio-oedema (AE) cases seen in the National Reference Centre of AE between 2000 and 2009. RESULTS: We found 26 patients (from 15 unrelated families) with type III HAE. All but four were women and presented with typical AE attacks, exacerbated by pregnancy or oral contraceptives containing oestrogens (OC). We also found that 54.5% of women were worsened with oestrogen and 23% were oestrogen dependent. All patients improved on long-term prophylactic tranexamic acid treatment; some acute attacks improved with C1Inh concentrate infusion. All of the patients had normal C1Inh and C4 levels. C1Inh function was also normal, except in women receiving OC or during a pregnancy: transient, moderately low levels (32-74% of the normal range) were found in 18 patients tested (67%). No SERPING1 gene mutation was found. Six patients from three unrelated families were heterozygous for an F12 gene variant. CONCLUSION: Diagnosis of type III HAE should be based on clinical (typical attacks, often hormonally influenced), laboratory (normal C1Inh antigenic protein) and genetic (F12 gene mutation) evidence.
Assuntos
Angioedemas Hereditários/diagnóstico , Angioedemas Hereditários/epidemiologia , Estudos de Coortes , Proteínas Inativadoras do Complemento 1/análise , Proteína Inibidora do Complemento C1 , Estrogênios/farmacologia , Fator XII/genética , Família , Feminino , França , Variação Genética , Humanos , Masculino , Gravidez , Estudos Retrospectivos , Ácido Tranexâmico/uso terapêuticoRESUMO
BACKGROUND: The inflammatory cascade has been hypothesized to be an important mechanism of post-ischaemic myocardial reperfusion injury and several studies demonstrated that C1 esterase inhibitor (C1-INH) is effective in post-ischaemia myocardial protection. Therefore, we aimed to investigate prospectively in a randomised double-blind study the cardioprotective effects of C1-INH in ST segment elevation myocardial infarction (STEMI) in patients who underwent emergent reperfusion with coronary artery bypass grafting (CABG). METHODS: In this study, we enrolled 80 patients affected with STEMI who underwent emergent CABG. Patients were assigned in two groups (C1-INH group: receive 1000 UI of C1-INH; and placebo group: receive a saline solution). The effects of C1-INH on complement inhibition, myocardial cell injury extension and clinical outcome were studied. Haemodynamic data and myocardial function were monitored. C1-INH, C3a, C4a complement activation fragments and cardiac troponin I (cTnI) serum levels were measured before, during and after surgery. RESULTS: Patient characteristics were not different between the two groups. The overall in-hospital mortality rate was 6.2%. No statistical significant difference was observed between the two groups with regard to early mortality (p=0.36). Statistical significant difference between the two groups was showed for cardiopulmonary bypass support (p=0.04), administration of high dose of inotropes drugs (p=0.001), time of intubation (p=0.03), intensive care unit (ICU) stay (p=0.04) and in-hospital stay (p=0.03). A significant improvement in mean arterial pressure (p=0.03), cardiac index (p=0.02) and stroke volume (p=0.03) was showed in C1-INH group versus placebo group. The serum cTnI levels were significantly low in the C1-INH group versus placebo group after reperfusion, during the observation period. Plasma levels of C3a and C4a complement fragments were reduced significantly in C1-INH group. No drugs-related adverse effects were observed. CONCLUSIONS: The inhibition of the classic complement pathway by C1-INH appears to be an effective mean of preserving ischaemic myocardium from reperfusion injury as demonstrated by low serum cTnI levels in C1-INH group. Therefore, the use of C1-INH during CABG as a rescue therapy in STEMI patients is probably an effective treatment to inhibit complement activity and to improve cardiac function and haemodynamic performance without impacting early mortality. Large randomised study should be performed to support our results.
Assuntos
Cardiotônicos/administração & dosagem , Proteínas Inativadoras do Complemento 1/administração & dosagem , Inativadores do Complemento/administração & dosagem , Infarto do Miocárdio/tratamento farmacológico , Reperfusão Miocárdica/métodos , Cardiotônicos/efeitos adversos , Cardiotônicos/análise , Proteínas Inativadoras do Complemento 1/efeitos adversos , Proteínas Inativadoras do Complemento 1/análise , Complemento C3a/análise , Complemento C4a/análise , Inativadores do Complemento/efeitos adversos , Inativadores do Complemento/análise , Ponte de Artéria Coronária/métodos , Método Duplo-Cego , Feminino , Humanos , Infusões Intravenosas , Masculino , Pessoa de Meia-Idade , Contração Miocárdica/efeitos dos fármacos , Infarto do Miocárdio/mortalidade , Infarto do Miocárdio/cirurgia , Estudos Prospectivos , Resultado do Tratamento , Troponina I/sangueRESUMO
INTRODUCTION: We report angioedema as a rare presentation leading to a diagnosis of systemic lupus erythematosus (SLE). CLINICAL PICTURE: A diagnosis of angioedema was delayed in a patient presenting with limb and facial swelling until she developed acute upper airway compromise. After excluding allergic and hereditary angioedema, acquired angioedema (AAE) was suspected, possibly precipitated by respiratory tract infection. Associated clinical and laboratory features led to a diagnosis of SLE. TREATMENT: Management proved challenging and included high dose steroids and immunosuppressants. OUTCOME: The patient responded to treatment and remains in remission without recurrence of the angioedema. CONCLUSION: AAE occurs due to the acquired deficiency of inhibitor of C1 component of complement (C1 INH). Lymphoproliferative disorders and anti-C1 INH antibodies are well-described associations. However, one should also consider the possibility of SLE.
Assuntos
Angioedema/etiologia , Lúpus Eritematoso Sistêmico/diagnóstico , Lúpus Eritematoso Sistêmico/etiologia , Angioedema/sangue , Angioedema/fisiopatologia , Angioedema/terapia , Síndrome Antifosfolipídica/diagnóstico , Síndrome Antifosfolipídica/etiologia , Encéfalo/patologia , Proteínas Inativadoras do Complemento 1/análise , Proteínas Inativadoras do Complemento 1/deficiência , Feminino , Humanos , Lúpus Eritematoso Sistêmico/complicações , Imageamento por Ressonância Magnética , Pessoa de Meia-Idade , Respiração Artificial , Insuficiência Respiratória/etiologia , Insuficiência Respiratória/terapiaRESUMO
We describe a chip-based immunoassay for multiplex antigen detection, based on the self-assembly of semi-synthetic DNA-protein conjugates to generate an easily configurable protein microarray. The general principle of this microarray-fluorescence immunoassay (microFIA) is similar to that of a two-sided (sandwich) immunoassay. However, covalent single-stranded DNA-streptavidin conjugates are employed for the efficient immobilization of biotinylated capture antibodies through hybridization to complementary surface-bound DNA oligomers. In a model system, we use the DNA-directed immobilization (DDI) of antibodies to generate an antibody microarray for the parallel detection of the tumor marker human carcinoembryonic antigen (CEA), recombinant mistletoe lectin rViscumin (rVis), ceruloplasmin (CEP), and complement-1-inactivator (C1A) in human blood serum samples. Detection limits down to 400 pg mL(-1) are reached. In addition, we describe a method for the internal standardization of protein microarray analyses, based on the simultaneous measurement of constant amounts of the blood proteins CEP and C1 A, intrinsically present in human serum, to compensate for interexperimental variations usually occurring in microarray analyses. The standardization leads to a significantly higher data reliability and reproducibility in intra- and interassay measurements. We further demonstrate that the DDI-microFIA can also be carried out in a single step by tagging of the analyte simultaneously with both capture and detection antibody and subsequent immobilization of the immunocomplex formed, on the DNA microarray capture matrix. This protocol significantly reduces handling time and costs of analysis.
Assuntos
DNA/química , Imunoensaio/instrumentação , Imunoensaio/métodos , Análise de Sequência com Séries de Oligonucleotídeos , Proteínas/química , Anticorpos/química , Anticorpos/imunologia , Sequência de Bases , Antígeno Carcinoembrionário/sangue , Ceruloplasmina/análise , Proteínas Inativadoras do Complemento 1/análise , Fluorescência , Humanos , Lectinas/sangue , Reprodutibilidade dos TestesRESUMO
Acquired C1 esterase inhibitor deficiency is a rare condition, usually presenting after the 2nd decade of life, and is often related to underlying conditions such as autoimmune and lymphoproliferative disorders. This case report describes a man whose initial clinical presentation with acute angioedema and whose initial estimation of a low C1 esterase inhibitor concentration indicated that he had an acquired angioedema, possibly secondary to a B cell neoplasm. A paraprotein was detected, and although its detection was serendipitous because it hinged on a spurious C1 esterase inhibitor result, this case confirms the role of C4 concentrations in the investigation of C1 esterase inhibitor deficiency. It also confirms the need to obtain repeat confirmatory samples before arriving at a diagnosis, however convincing the clinical signs may be.
Assuntos
Angioedema/sangue , Proteínas Inativadoras do Complemento 1/deficiência , Doenças da Boca/sangue , Paraproteínas/análise , Doença Aguda , Idoso , Biomarcadores/sangue , Proteínas Inativadoras do Complemento 1/análise , Complemento C4/análise , Humanos , Masculino , Nefelometria e Turbidimetria/instrumentação , Nefelometria e Turbidimetria/normas , Sensibilidade e EspecificidadeRESUMO
Few data are available on measurements of serum concentrations of complement proteins in inflammatory bowel disease (IBD). Therefore we measured serum levels of C3, C4, and C1-esterase inhibitor (C1-INH) as well as C-reactive protein (CRP) in 167 patients with Crohn's disease (CD) and 111 patients with ulcerative colitis (UC). Median serum concentrations of C3 and C1-INH were significantly higher in CD than in UC. According to multiple logistic regression analysis adjusted to age, sex, activity of disease, and presence of extraintestinal manifestations, IBD patients with high-normal (> or = 128%, > or = 75th percentile ) C1-INH concentrations had significantly (0.0275) higher odds ratio to have a diagnosis of CD than UC. Patients with high-normal C3 (> or = 1.40 g/liter) and high (> or =20 mg/liter) CRP concentrations had an even higher odds ratio of a CD diagnosis (P = 0.0132). Our findings indicate that measurement of C3, C1-INH, and CRP can be used as an additional marker to pANCA/ASCA for distinguishing patients with CD and UC.
Assuntos
Colite Ulcerativa/sangue , Proteínas Inativadoras do Complemento 1/análise , Complemento C3/análise , Complemento C4/análise , Doença de Crohn/sangue , Adulto , Proteína C-Reativa/análise , Feminino , Humanos , Modelos Logísticos , MasculinoRESUMO
Although frequently reported as an aetiology for chronic angioneurotic oedema or urticaria, food allergy is often a diagnosis proposed in the absence of more convincing evidence, as illustrated by the disappointing results of eviction regimens. We report a series of women with an initial diagnosis of food allergy, but in whom the role of oral contraceptives was subsequently demonstrated. Detailed medical history was obtained from 26 young women presenting with chronic angioneurotic oedema or urticaria initially attributed to food allergy, but in whom C1-esterase inhibitor (C1 INH) deficiency was demonstrated. We investigated the effects of oral contraception on C1 INH levels, C1 INH activity and clinical symptoms of these patients. Discontinuation of oral contraception induced an increase in C1 INH levels and C1 INH activity, associated with recovery or marked improvement of the clinical symptoms formerly attributed to food allergy. The relatively high frequency of women taking cyproterone acetate in this population appeared to be a remarkable finding. Replacement of the initial contraception containing ethinylestradiol by a progestogen maintained or even accentuated these good therapeutic results. Exogenous oestrogens, such as those contained in most oral contraceptives, may play an iatrogenic role in the aetiology of chronic angioneurotic oedema or urticaria.
Assuntos
Angioedema/etiologia , Estrogênios/efeitos adversos , Hipersensibilidade Alimentar/complicações , Adolescente , Adulto , Angioedema/sangue , Angioedema/terapia , Criança , Proteínas Inativadoras do Complemento 1/análise , Proteínas Inativadoras do Complemento 1/deficiência , Anticoncepcionais Orais Hormonais/efeitos adversos , Acetato de Ciproterona , Feminino , Humanos , Pessoa de Meia-Idade , Valores de Referência , Indução de Remissão , Estudos RetrospectivosRESUMO
PURPOSE: Acquired angioedema type 1 is characterized by a C1 inhibitor deficiency in patients with lymphoproliferative disorders, whereas acquired angioedema type 2 is characterized by anti-C1 inhibitor antibodies, and has not been thought to be associated with lymphoproliferative disease. We studied the clinical features, complement profiles, and associated diseases in 19 new patients with diagnosed acquired angioedema type 2. SUBJECTS AND METHODS: Plasma concentrations and functional activity of complement components were measured by conventional techniques. Functional C1 inhibitor activity was assessed by a chromogenic assay. Autoantibodies to C1 inhibitor were detected using an enzyme-linked immunosorbent assay. RESULTS: The 11 men and 8 women (median age, 60 years) presented with recurrent attacks of angioedema. All patients had detectable anti-C1 inhibitor antibodies in serum. A monoclonal gammopathy was detected in 12 patients (63%) at the time of diagnosis, 11 of whom had an immunoglobulin peak of the same heavy- and light-chain isotypes as the acquired anti-C1 inhibitor antibody. Three of these 12 patients developed a malignant lymphoproliferative disease. CONCLUSION: As with type 1 disease, a large proportion of patients with acquired angioedema type 2 have a lymphoproliferative disorder.
Assuntos
Angioedema/epidemiologia , Angioedema/imunologia , Anticorpos Anti-Idiotípicos/imunologia , Proteínas Inativadoras do Complemento 1/imunologia , Paraproteinemias/diagnóstico , Paraproteinemias/epidemiologia , Distribuição por Idade , Idoso , Angioedema/diagnóstico , Anticorpos Anti-Idiotípicos/análise , Western Blotting , Estudos de Coortes , Comorbidade , Proteínas Inativadoras do Complemento 1/análise , Ensaio de Imunoadsorção Enzimática , Feminino , Seguimentos , Humanos , Imunoglobulina A/análise , Imunoglobulina G/análise , Imunoglobulina M/análise , Transtornos Linfoproliferativos/epidemiologia , Transtornos Linfoproliferativos/imunologia , Masculino , Pessoa de Meia-Idade , Prevalência , Medição de Risco , Distribuição por SexoRESUMO
This prospective study investigated the role of reduced hepatic synthesis of regulating proteins in coagulopathy after partial hepatectomy (PH) compared with major abdominal surgery (MAS) without involvement of the liver. Furthermore, we studied the effect of rBPI21, an endotoxin-neutralizing agent, on coagulopathy after PH was studied. Compared with MAS, PH resulted in significantly elevated levels of thrombin-antithrombin-III and plasmin-alpha2-antiplasmin complexes. Levels of antithrombin-3, alpha2-antiplasmin, fibrinogen, plasminogen, alpha2-macroglobulin (alpha2-M), and C1-inhibitor remained lower following PH. Treatment with rBPI21 led to significantly lower levels of tissue-type plasminogen activator (t-PA). Post-operative disseminated intravascular coagulation (DIC) was associated with significantly higher bilirubin and t-PA plasma levels and significantly lower levels of alpha2-M. This study indicates that PH induced hepatic failure results in decreased synthesis of hepatic regulating plasma proteins and subsequent activation of coagulation and fibrinolysis. Prevention of t-PA release by rBPI21 may have important clinical implications. Decreased availability of alpha2-M may be a factor in post-operative DIC.
Assuntos
Fatores de Coagulação Sanguínea/biossíntese , Coagulação Intravascular Disseminada/etiologia , Endotoxemia/etiologia , Hepatectomia/efeitos adversos , Fígado/metabolismo , Proteínas de Membrana/uso terapêutico , Abdome/cirurgia , Adulto , Idoso , Antitrombina III/análise , Translocação Bacteriana , Bilirrubina/sangue , Biomarcadores/sangue , Comorbidade , Proteínas Inativadoras do Complemento 1/análise , Coagulação Intravascular Disseminada/metabolismo , Coagulação Intravascular Disseminada/prevenção & controle , Método Duplo-Cego , Endotoxemia/metabolismo , Endotoxinas/antagonistas & inibidores , Feminino , Fibrinogênio/análise , Fibrinólise , Neoplasias Gastrointestinais/sangue , Neoplasias Gastrointestinais/cirurgia , Humanos , Imunoglobulina G/sangue , Interleucina-6/sangue , Células de Kupffer/metabolismo , Hepatopatias/sangue , Hepatopatias/cirurgia , Falência Hepática/sangue , Falência Hepática/etiologia , Masculino , Proteínas de Membrana/farmacologia , Pessoa de Meia-Idade , Peptídeo Hidrolases/análise , Plasminogênio/análise , Período Pós-Operatório , Estudos Prospectivos , Sepse/etiologia , Ativador de Plasminogênio Tecidual/análise , alfa 2-Antiplasmina/análise , alfa-Macroglobulinas/análiseRESUMO
OBJECTIVE: To find out if microheterogeneous changes--such as in molecular weight, isoelectric point, electrophoretic mobility, lectin binding or complexation of the C1-esterase inhibitor--exist in plasma samples from various subgroups of patients. If so, whether these differences could be used diagnostically in single plasma samples from patients with cancer for prognostic assessment of operability or risk of recurrence, and whether any change indicated an increased risk for development of postoperative complications. DESIGN: Retrospective study. SETTING: University hospital, Sweden. SUBJECTS: 16 patients operated on as emergencies for acute peritonitis, 118 patients electively operated on for benign diseases, 274 patients electively operated on for cancer, and 212 patients admitted with acute abdominal pain. MAIN OUTCOME MEASURES: Curative operation, diagnoses, postoperative complications, recurrence of cancer within 2 years. RESULTS: There were no biochemical differences in the C1-esterase inhibitor between single or sequential plasma samples from four large groups of patients with benign disease, cancer, or inflammatory disease, with operable or inoperable cancer, with postoperative complications or not, or with or without early recurrence of cancer. CONCLUSIONS: Specialised biochemical analyses of C1-esterase inhibitor, the most important plasma protease inhibitor of the complement and kinin systems and of contact activation in plasma, cannot be used for prognostic assessment of operability, risk of postoperative complications, or risk of recurrence in patients with cancer.
Assuntos
Proteínas Inativadoras do Complemento 1/análise , Neoplasias/diagnóstico , Neoplasias/cirurgia , Complicações Pós-Operatórias/diagnóstico , Abdome Agudo/diagnóstico , Abdome Agudo/cirurgia , Doença Aguda , Biomarcadores/análise , Feminino , Humanos , Imunoensaio , Masculino , Peritonite/diagnóstico , Peritonite/cirurgia , Valor Preditivo dos Testes , Cuidados Pré-Operatórios , Prognóstico , Recidiva , Estudos Retrospectivos , Sensibilidade e EspecificidadeRESUMO
We present the first reported case of hereditary angioedema (HAE) with gastric involvement to be successfully evaluated by endoscopy both during and after an attack. A 31-year-old man who had a family history of angioedema was admitted to our hospital with complaints of abdominal pain and swelling of extremities. Computed tomography scan and endoscopy carried out during this attack revealed transient gastrointestinal wall edema which, along with decreased levels of serum C4 and C1 inhibitor, confirmed the diagnosis of HAE with gastrointestinal involvement. During the attack, the gastric mucosa was erythematous and edematous, and parts of its surface bulged into the gastric lumen, resembling a submucosal tumor, as a result of massive submucosal edema. During the healing process, a number of small nodules and raised erosions developed over the entire gastric mucosal surface after healing of prominent gastric edema. Within 55 days, the gastric mucosa had returned to normal. The endoscopic findings for the stomach in HAE have not, to our knowledge, been previously described.
Assuntos
Angioedema/genética , Angioedema/patologia , Endoscopia Gastrointestinal , Mucosa Gástrica/patologia , Mucosa Intestinal/patologia , Adulto , Proteínas Inativadoras do Complemento 1/análise , Complemento C4/análise , Humanos , MasculinoRESUMO
In situ and in vitro studies suggest that activation of locally produced complement factors may act as a mediator between amyloid deposits and neurodegenerative changes seen in Alzheimer's disease (AD). C1-esterase inhibitor (C1-Inh), which regulates activation of C1 of the complement classical pathway, can be detected immunohistochemically in its inactivated form in activated astrocytes and dystrophic neurites in AD plaque areas. In this study, designed to investigate the cellular source of C1-Inh, C1-Inh was found to be secreted in a functionally active form by astrocytes cultured from postmortem human brain specimens as well as by neuroblastoma cell lines. Recombinant human interferon-gamma (IFN-gamma), which stimulates C1-Inh synthesis in various cell types, several-fold stimulated C1-Inh protein secretion by cultured human astrocytes derived from different regions of the central nervous system and by one (SK-N-SH) of two neuroblastoma cell lines (SK-N-SH and IMR-32) included in this study. In contrast to IFN-gamma, other cytokines [interleukin (IL)-1beta, IL-6 and tumor necrosis factor (TNF)-alpha] that can be found in brain areas affected by AD, did not stimulate C1-Inh secretion by astrocytes or neuroblastomas in vitro. This inability to secrete C1-Inh is probably due to unresponsiveness at the transcriptional level, since C1-Inh secretion paralleled the expression of the 2.1-kb C1-Inh mRNA. In situ hybridization with a C1-Inh RNA antisense probe labeled neurons rather than astrocytes, suggesting a role for neurons as producers of complement regulatory proteins in vivo. Since IFN-gamma is apparently lacking in the brain parenchyma, and amyloid plaque-associated cytokines (IL-1beta, IL-6, TNF-alpha) do not stimulate C1-Inh expression in vitro, the nature of the stimulus responsible for neuronal C1-Inh expression in AD brains remains to be investigated.
Assuntos
Doença de Alzheimer/metabolismo , Proteínas Inativadoras do Complemento 1/análise , Proteínas Inativadoras do Complemento 1/metabolismo , Idoso , Idoso de 80 Anos ou mais , Doença de Alzheimer/patologia , Células Cultivadas , Proteínas Inativadoras do Complemento 1/genética , Feminino , Hipocampo/patologia , Humanos , Hibridização In Situ , Interferon gama/farmacologia , Interleucina-1/fisiologia , Interleucina-6/fisiologia , Masculino , Pessoa de Meia-Idade , Córtex Pré-Frontal/citologia , Sondas RNA/metabolismo , RNA Mensageiro/análise , RNA Mensageiro/biossíntese , RNA Mensageiro/efeitos dos fármacos , Lobo Temporal/patologia , Células Tumorais Cultivadas , Fator de Necrose Tumoral alfa/fisiologiaRESUMO
OBJECTIVE: To find out whether concentrations of albumin (reflecting nutritional state), C-reactive protein (reflecting an acute phase reaction) or plasma protease inhibitors (reflecting ongoing proteolysis) are good predictors of postoperative complications, and whether other biochemical tests may improve diagnostic accuracy. DESIGN: Retrospective study. SETTING: University hospital, Sweden. SUBJECTS: 260 patients undergoing elective surgery for malignant (n = 149) or benign (n = 111) disease. MAIN OUTCOME MEASURES: Preoperative biochemical plasma measurements and postoperative complications. RESULTS: 192 patients recovered uneventfully and 35 had minor and 33 major postoperative complications. An increased plasma C-reactive protein concentration preoperatively, as well as a reduced albumin concentration, predicted the risk of developing major postoperative complications. Measurement of plasma protease inhibitors (C1-esterase inhibitor, alpha-2-macroglobulin and antithrombin III), specific biochemical studies of microheterogeneity, or comparison of quantitative and functional concentrations of the inhibitors gave no additional information. CONCLUSION: One measurement of the C-reactive protein and albumin concentrations preoperatively will identify patients at risk of developing severe postoperative complications.