Antibodies to the atherosclerotic plaque components beta2-glycoprotein I and heat-shock proteins as risk factors for acute cerebral ischemia.

One third of cases of cerebral ischemia have no clear etiology. A humoral response to the atherosclerotic plaques components beta2-glycoprotein l (beta2-gpl) and heat-shock proteins (Hsp) might be involved in the pathogenesis of stroke. This case-control study includes a complete profile of anti-beta2-gpl antibodies and testing of IgG antibodies to the 60/65 kilodaltons (kDa) Hsp in stroke patients. Ninety-three patients with acute ischemic stroke and 93 controls were evaluated for age, sex, race, hypertension, smoking, previous cardiopathy, diabetes mellitus, hypercholesterolemia and previous history of cerebral ischemia. lgG/lgM/lgA anticardiolipin (aCL) and anti-beta2-gpl antibodies, as well as lgG antibodies to human 60 kDa Hsp and to Mycobacterium bovis 65 kDa Hsp, were detected by immunoassay. Adjusted odds ratios (OR) were calculated by logistic regression. The adjusted OR for IgA anti-beta2-gpl antibodies was 4.6 (90%Cl 1.5 to 14.3; p = 0.025). The non-adjusted OR for IgG antibodies to Hsp 60 was 26.1. The adjusted OR for IgG antibodies to Hsp 65 was 3.2 (90%Cl 1.2 to 8.3; p = 0.044). The adjusted OR for lgG to any Hsp (60 or 65) was 4.8 (90%Cl 1.9 to 12.1; p = 0.006). This study demonstrates that elevated IgA anti-beta2-gpl and lgG anti-Hsp 60/65 antibodies are associated with increased risk of ischemic stroke. The association occurred independently of other risk factors. This humoral response might link autoimmunity, thrombophilia and atherosclerosis in stroke patients.

Anti-beta2-glycoprotein I antibodies as risk factors for acute myocardial infarction.

OBJECTIVE: To determine whether high levels of antibodies against the phospholipid beta2-glycoprotein I (beta2-gpI) cofactor are associated with an increase in the risk of acute myocardial infarction. METHODS: The study comprised 82 patients with acute myocardial infarction and 82 controls, who were assessed in regard to age, sex, race, hypertension, smoking, previous heart disease, history of diabetes mellitus, and hypercholesterolemia. The following antibodies were detected using immunoassay: anticardiolipin and anti-beta2-gpI IgA, IgG, and IgM. Adjusted odds ratios (OR) for risk factors were obtained through logistic regression. RESULTS: The mean ages of the cases and controls were, respectively, 57.7 and 51.1 years (P=0.003). Men (P=0.005) and the white race predominated in both groups (P=0.798). Of the risk factors, a history of diabetes (OR=5.3; 95% CI: 1.9 to 14.9; P=0.001) and previous heart disease (OR=4.7; 95% CI: 2.0 to 10.7; P<0.001) were the most consistent associations with myocardial infarction. The frequency of anticardiolipin IgG, IgM, and IgA antibodies did not differ between cases and controls (P=1.000). Anti-beta2-gpI IgA antibodies were more frequent in cases than in controls (P=0.054). The adjusted OR for anti-beta2-gpI IgA antibodies was 3.4 (95% CI: 1.3 to 9.1; P=0.015). CONCLUSION: Anti-beta2-gpI IgA antibodies, but not anticardiolipin antibodies, seemed to behave as independent risk factors for myocardial infarction, which may represent a link between autoimmunity and atherosclerosis in patients with acute myocardial infarction.

[Antibodies to beta2-glycoprotein I, autoimmunity and atherosclerosis]. / Anticorpos contra beta2-glicoproteína I, autoimunidade e aterosclerose.

Beta2-glycoprotein I (beta2-gpI) is a phospholipid cofactor with anticoagulant properties. A number of biological functions in the coagulation cascade have been attributed to this cofactor. Sera from patients with antiphospholipid syndrome (APS) frequently react to beta2-gpI in immunoassays. Occasionally, patients with thrombotic diathesis present anti-beta2-gpI antibodies in the absence of other antiphospholipid antibodies (APA). More recently, the presence of beta2-gpI in the atherosclerotic plaque has been proved. In this article, we initially approach the physiological functions of beta2-gpI in the coagulation cascade, and we also review the importance of anti-beta2gpI antibodies in patients with APS, systemic lupus erythematosus (SLE) and infections. Lastly, we focus the role of anti-beta2-gpI antibodies in coronary and cerebral atherosclerosis.

Anticorpos contra beta2-glicoproteína I, autoimunidade e aterosclerose / Antibodies to beta2-glycoprotein I, autoimmunity and atherosclerosis

A beta2-glicoproteína I (beta2-gpI) é uma fator fosfolipídico com propriedades anticoagulantes. Inúmeras funções biológicas na via da coagulação são atribuídas a este cofator. Os soros de pacientes com síndrome antifosfolipídica (SAF) freqüentemente reagem contra beta2-pgI em ensaios imunoenzimáticos. Por vezes, pacientes com diátese trombótica apresentam anticorpos anti-beta2-gpI na ausência de outros anticorpos anti-fosfolípides (AAF). Mais recentemente, comprovou-se a presença da beta2-gpI na placa aterosclerótica. Nesta revisão, abordamos inicialmente as funções fisiológicas da beta2-gpI na via da coagulação. A seguir, revisamos a importância dos anticorpos anti-beta2gpI em pacientes com SAF, outras diáteses trombóticas, lúpus eritematoso sistêmico (LES) e infecções. Por fim, o papel dos anticorpos anti-beta2gpI na aterosclerose coronária e cerebral é também abordado.

Anticorpos contra beta2-glicoproteína I como fatores de risco para infarto agudo do miocárdio / Anti-beta2-glycoprotein I antibodies as risk factors for acute myocardial infarction

OBJETIVO: Determinar se títulos elevados de anticorpos contra o cofator fosfolipídico beta2-glicoproteína I (beta2-gpI) se associam a risco aumentado de infarto agudo do miocárdio. MÉTODOS: Incluídos 82 pacientes com infarto agudo do miocárdio e 82 controles, avaliados quanto à idade, sexo, raça, hipertensão, tabagismo, cardiopatia prévia, história de diabetes mellitus e hipercolesterolemia. Anticorpos anticardiolipina e antibeta2-gpI IgA, IgG e IgM foram detectados por imunoensaio. Odds ratios (OR) ajustados para fatores de risco foram obtidos através de regressão logística. RESULTADOS: A média de idade para casos e controles foi, respectivamente, de 57,7 e 51,1 anos (P=0,003), predominando homens (P=0.005) e a raça branca em ambos os grupos (P = 0.798). Entre os fatores de risco, história de diabetes (OR 5,3; IC95 por cento 1,9 a 14,9; P=0,001) e cardiopatia prévia (OR 4,7; IC95 por cento 2,0 a 10,7; P<0,001) foram as associações mais consistentes com o infarto do miocárdio. A freqüência de anticorpos anticardiolipina IgG, IgM e IgA não diferiu em casos e controles (P=1,000). Anticorpos IgA contra beta2-gpI IgA foram mais freqüentes em casos do que em controles (P=0.054). O OR ajustado para anticorpos IgA anti-beta2-gpI IgA foi 3,4 (IC95 por cento 1,3 a 9,1; P = 0,015). CONCLUSAO: Anticorpos IgA antibeta2-gpI, mas não anticardiolipina, parecem se comportar como fatores de risco independentes para o infarto, o que pode representar um elo entre autoimunidade e aterosclerose em pacientes com infarto agudo do miocárdio.

Antibodies to the atherosclerotic plaque components beta2-glycoprotein I and heat-shock proteins as risk factors for acute cerebral ischemia

One third of cases of cerebral ischemia have no clear etiology. A humoral response to the atherosclerotic plaques components beta2-glycoprotein l (beta2-gpl) and heat-shock proteins (Hsp) might be involved in the pathogenesis of stroke. This case-control study includes a complete profile of anti-beta2-gpl antibodies and testing of IgG antibodies to the 60/65 kilodaltons (kDa) Hsp in stroke patients. Ninety-three patients with acute ischemic stroke and 93 controls were evaluated for age, sex, race, hypertension, smoking, previous cardiopathy, diabetes mellitus, hypercholesterolemia and previous history of cerebral ischemia. lgG/lgM/lgA anticardiolipin (aCL) and anti-beta2-gpl antibodies, as well as lgG antibodies to human 60 kDa Hsp and to Mycobacterium bovis 65 kDa Hsp, were detected by immunoassay. Adjusted odds ratios (OR) were calculated by logistic regression. The adjusted OR for IgA anti-beta2-gpl antibodies was 4.6 (90 percentCl 1.5 to 14.3; p = 0.025). The non-adjusted OR for IgG antibodies to Hsp 60 was 26.1. The adjusted OR for IgG antibodies to Hsp 65 was 3.2 (90 percentCl 1.2 to 8.3; p = 0.044). The adjusted OR for lgG to any Hsp (60 or 65) was 4.8 (90 percentCl 1.9 to 12.1; p = 0.006). This study demonstrates that elevated IgA anti-beta2-gpl and lgG anti-Hsp 60/65 antibodies are associated with increased risk of ischemic stroke. The association occurred independently of other risk factors. This humoral response might link autoimmunity, thrombophilia and atherosclerosis in stroke patients