Circulating immune complexes in atherosclerotic vascular disease

We have investigated the association of the humoral immune factors circulating immune complexes (CICs) and autoantibodies against cardiolipin (aCL) and oxidatively modified LDL (oxLDL) to atherosclerotic vascular diseases.

In a prospective nested case-control study, in which healthy 50-year-old men were followed for 20 years, the prevalence of elevated CICs and the concentration of CICs were higher in men who developed myocardial infarction. (MI) than in those who remained healthy. CICs was a strong and independent risk factor. There was a positive relation between the levels of CICs and IgG-aCL in men who developed Nil. The level of IgG-aCL and the prevalence of elevated IgG- and IgM-aCL 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.

In a five-year prospective study, CICs and antibodies against oxLDL were associated with progression of coronary atherosclerosis in young dyshpoproteinemic men suffering from coronary artery disease.

In 18% of patients who had survived a premature MI, CICs were present in high concentrations many years after the event. Antibodies of the IgG isotype predominated in CICs. Half of the patients with persistent high CICs had alimentary proteins in the immune complexes. A rise in CICs, signs of activation of the complement cascade, and a rise in plasma concentrations of vonWillebrand factor antigen were evident within one week in four young patients subjected to a 2-week elimination diet followed by challenge with the alimentary antigen in question.

Elevated levels of CICs were present in patients with premature peripheral atherosclerosis and null alleles of C4A (C4A*QO) enhanced the propensity to ICs formation.

CICs were increased in patients with diabetes, and especially in those with vascular complications. The concentrations of aCL were relatively higher in CICs than in serum. The concentration and prevalence of CICs were increased in patients with C4A*QO. Patients with vascular complications had more often C4A*QO than C4B*QO.

List of scientific papers

I. Mustafa A, Nityanand S, Berglund L, Lithell H, Lefvert AK (2000). "Circulating immune complexes in 50-year-old men as a strong and independent risk factor for myocardial infarction. " Circulation 102(21): 2576-81
https://pubmed.ncbi.nlm.nih.gov/11085959

II. Mustafa A, Ruotolo G, Ericsson CG, Nilsson J, de Faire U, Hamsten A, Lefvert AK (2001). "Role of circulating immune complexes and autoantibodies against modified LDL and cardiolipin in the progression of premature coronary atherosclerosis." (Submitted)

III. Mustafa A, Hamsten A, Holm G, Lefvert AK (2001). "Circulating immune complexes induced by food proteins implicated in precocious myocardial infarction. " Ann Med 33(2): 103-12
https://pubmed.ncbi.nlm.nih.gov/11327113

IV. Nityanand S, Truedsson L, Mustafa A, Bergmark C, Lefvert AK (1999). "Circulating immune complexes and complement C4 null alleles in patients in patients operated on for premature atherosclerotic peripheral vascular disease. " J Clin Immunol 19(6): 406-13
https://pubmed.ncbi.nlm.nih.gov/10634214

V. Ahmed E, Nityanand S, Mustafa A, Brismar K, Lefvert AK (1999). "Anti-cardiolipin antibodies and circulating immune complexes in type 1 diabetes mellitus: increased prevalence and relation to vascular complications. " Clin Exp Immunol 115(2): 255-9
https://pubmed.ncbi.nlm.nih.gov/9933450