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Abstract —Atherosclerosis is an inflammatory disease, and the involvement of immune mechanisms in disease progression is increasingly recognized. Immunization with oxidized low density lipoprotein (LDL) decreases atherosclerosis in several animal models. To explore humoral and cellular immune reactions involved in this protection, we immunized apolipoprotein E knockout mice with either homologous plaque homogenates or homologous malondialdehyde (MDA)-LDL. Immunization with both these antigen preparations reduced lesion development. The plaques contained immunogen(s) sharing epitopes on MDA-LDL, MDA–very low density lipoprotein, and oxidized cardiolipin. This shows that a T-cell–dependent antibody response was associated with protection against atherosclerosis. The protection was associated with specific T-cell–dependent elevation of IgG antibodies against MDA-LDL and oxidized phospholipids, and the increased titers of IgG antibodies were correlated with decreased lesion formation and lower serum cholesterol levels.

Background —Circulating immune complexes (CICs) and autoantibodies against oxidatively modified LDLs (oxLDLs) and cardiolipin occur in patients with atherosclerosis and myocardial infarction (MI). The ability of such CICs and antibodies to predict myocardial infarction (MI) was investigated in a prospective nested case-control study in which healthy 50-year-old men were followed for 20 years. Methods and Results —Two hundred fifty-seven men were included in the study, and 119 developed MI (39 died) between 50 and 70 years of age. One hundred thirty-eight randomly chosen men who did not develop MI up to 70 years of age served as controls. The prevalence of elevated levels of CICs and the concentration of CICs in men who developed MI were higher than in those who remained healthy. The concentration of CICs at age 50 was associated with a marked increased risk for MI, and this risk was independent of other conventionally recognized risk factors. There was a positive correlation between the levels of CIC and IgG antibodies to cardiolipin in men who developed MI. The level of IgG antibodies and the prevalence of elevated IgG and IgM antibodies to cardiolipin were higher in those who developed MI and had CICs than in those without CICs. Among men homozygous for C4 null alleles, those who developed MI had higher concentrations of CICs than did those who remained healthy. Conclusions —This prospective study shows that CICs alone or in combination with autoantibodies against cardiolipin in healthy males at 50 years of age predict subsequent MI between the age of and 70 years.

Background and Purpose —Anticardiolipin antibodies (aCL) have been proposed to be an independent risk factor for stroke. To test this hypothesis, a nested case-control study was performed to compare aCL with the other known risk factors for stroke. Methods —Within the framework of the World Health Organization Multinational Moni toring of Trends and Determinants in Ca rdiovascular Disease (MONICA) project and the Västerbotten Intervention Program (VIP) health survey, 44 725 men and women were enrolled and followed up from January 1, 1985, through August 31, 1996. Individuals free from cardiovascular events were followed up, and 123 developed stroke (on average, 34.1 months after blood sampling; 21 cerebral hemorrhage and 102 cerebral infarction); they were compared with 241 age- and sex-matched control subjects from the same population. ELISA was used for the analysis of IgG, IgM, and IgA aCL. Results —IgM-aCL were present in 11.4% of patients (14/123) who developed stroke and in 4.1% of individuals (10/241) who remained healthy ( P =0.013, OR 2.97, 95% CI 1.28 to 6.89). The OR for the levels of IgM-aCL was 1.34 ( P =0.01, 95% CI 1.07 to 1.68) without adjustment for other risk factors and 1.24 when adjusted for hypertension, diabetes mellitus, cigarette smoking, and use of smokeless tobacco ( P =0.077, 95% CI 0.98 to 1.56). There was no difference between patients and controls for the prevalence or level of IgG-aCL and IgA-aCL and also no difference between patients with cerebral hemorrhage and cerebral infarction for the prevalence of all 3 isotypes of aCL. Conclusions —We conclude that aCL are associated with future stroke but do not constitute an independent risk factor.

Abstract One hundred patients who had survived a myocardial infarction before the age of 45 years and 90 age- and sex-matched healthy individuals were investigated for circulating immune complexes (CICs) and the presence of complement C4 null alleles (C4Q0). CICs were found in increased concentrations in 20% of patients and 6.7% of control subjects. Patients and control subjects had the same prevalence of C4Q0. CICs were present in all patients and in 36% of the control subjects homozygous for C4Q0. Patients and control subjects heterozygous for C4Q0 had CICs in 71% and 0%, respectively. The high prevalence and a high concentration of CICs were particularly associated with C4A*Q0. Patients homozygous for C4A*Q0 had concentrations of LDL that were lower than found in other patients. The increased concentration of CICs associated with genetic deficiencies of the complement factor C4 might thus be an additional etiological factor for the development of chronic vascular damage and premature myocardial infarction.

We studied 17 children born to 15 myasthenic mothers; 2 of the infants had neonatal myasthenia pravis. Pyridostigmine was transferred to the child and accumulated in the amniotic fluid. Sixteen children had receptor antibodies at birth. In the affected infants, the half-life of the receptor antibody concentration was longer than it was in the others. Using an anti-idiotypic antibody, we found marked differences between the idiotypes in the mother and in affected children. Transient synthesis of receptor antibodies in the child seems to be a factor in the pathogenesis of nieonatal myasthenia gravis.