Is preclinical autoimmunity benign?: The case of cardiovascular disease

Abstract

Although there are many examples of autoantibodies in disease-free individuals, they can be a preclinical phenomenon heralding future autoimmune rheumatic disease. They may be a marker for autoreactive B-cell activation and other inflammatory autoimmune processes. The increased prevalence of cardiovascular disease (CVD) in autoimmune rheumatic diseases such as rheumatoid arthritis and systemic lupus erythematosus, and the increased risk of CVD in patients with rheumatic disease with autoantibodies, suggest that CVD may have autoimmune features. Autoantibodies might be risk markers for subclinical and clinical CVD development not only in patients with rheumatic diseases but in the general population as well.

Keywords: Autoantibodies; Autoimmunity; Cardiovascular disease; Coronary artery calcification; Intima media thickness; Preclinical.

Fig. 1

Phases in the development of pathogenic autoimmunity. Normal immunity progresses to benign autoimmunity through the influence of genetic composition and environment. Later, benign autoimmunity progresses to pathogenic autoimmunity. Symptoms of clinical illness appear soon after pathogenic autoimmunity develops. (From Arbuckle MR, McClain MT, Rubertone MV, et al. Development of autoantibodies before the clinical onset of systemic lupus erythematosus. N Engl J Med 2003;349:1532; with permission.)

Fig. 2

Connective tissue disease (CTD)-related autoimmunity might lead to inflammation and epitope spreading, which can progress to clinically active autoimmune CTD. It is hypothesized that the increased prevalence of atherosclerosis and subsequent cardiovascular events in autoimmune CTD is mediated by inflammation from disease activity. CTD-related autoimmunity might be independently associated with the development of atherosclerosis, which can be measured by the surrogate CAC or IMT. Subclinical atherosclerosis might then progress to clinical cardiovascular events.