The Contribution of Autoantibodies to Inflammatory Cardiovascular Pathology

Abstract

Chronic inflammation and resulting tissue damage underlie the vast majority of acquired cardiovascular disease (CVD), a general term encompassing a widely diverse array of conditions. Both innate and adaptive immune mechanisms contribute to chronic inflammation in CVD. Although maladies, such as atherosclerosis and cardiac fibrosis, are commonly conceptualized as disorders of inflammation, the cellular and molecular mechanisms that promote inflammation during the natural history of these diseases in human patients are not fully defined. Autoantibodies (AAbs) with specificity to self-derived epitopes accompany many forms of CVD in humans. Both adaptive/induced iAAbs (generated following cognate antigen encounter) and also autoantigen-reactive natural antibodies (produced independently of infection and in the absence of T cell help) have been demonstrated to modulate the natural history of multiple forms of CVD including atherosclerosis (atherosclerotic cardiovascular disease), dilated cardiomyopathy, and valvular heart disease. Despite the breadth of experimental evidence for the role of AAbs in CVD, there is a lack of consensus regarding their specific functions, primarily due to disparate conclusions reached, even when similar approaches and experimental models are used. In this review, we seek to summarize the current understanding of AAb function in CVD through critical assessment of the clinical and experimental evidence in this field. We additionally highlight the difficulty in translating observations made in animal models to human physiology and disease and provide a summary of unresolved questions that are critical to address in future studies.

IgG Anti-High Density Lipoprotein Antibodies Are Elevated in Abdominal Aortic Aneurysm and Associated with Lipid Profile and Clinical Features

“…Furthermore, the role of the humoral response remains unclear. In this respect, the relevance of autoantibodies for CVD has been previously appreciated [42,43], but there is scarce data regarding AAA [44]. Our findings add a new layer of evidence to this setting and expand the current knowledge on autoantibodies, namely anti-HDL antibodies, in AAA.…”

“…Another interesting finding from our study was the association between anti-HDL antibodies and clinical features, such as aortic diameter, a surrogate marker of AAA progression. Far from being innocent bystanders, autoantibodies are complex molecules with pleiotropic activities, including activation of immune cells bearing Fc receptors, leukocyte activation following immune complex deposition, complement fixation, and promoting tissue remodeling [42], which can explain the effects at the systemic level. As previously commented, anti-HDL antibodies have been connected to inflammatory pathways [22,24,27,49], which play a role as modulators of AAA progression [50].…”

Population-based estimates of humoral autoimmunity from the U.S. National Health and Nutrition Examination Surveys, 1960–2014

“…Autoantibodies are also increasingly identified as pathogenic in new ways beyond their role in classic AIDs. For example, autoantibodies have been identified as a potential cause of heart or lung disease in adults and may participate in the process of atherosclerosis [15][16][17][18][19][20][21]. A number of maternal autoantibodies show person-to-person transmission of disease to the developing fetus during pregnancy and may have adverse effects, the most outstanding is of these being neonatal lupus, neonatal thyroid disease and thyroid autoantibody related early fetal loss and pre-term birth [22][23][24][25][26][27].…”

Non-Linear Relationship between Anti-Apolipoprotein A-1 IgGs and Cardiovascular Outcomes in Patients with Acute Coronary Syndromes

“…Among the latter, both cellular and humoral autoimmune responses against different membrane proteins, native or modified lipoproteins have been shown to modulate the course of atherogenesis either in a pro- or anti-atherogenic manner [4,5]. Reflecting this intrinsic biological complexity, several autoantibodies have been detected in sera of individuals and associated either with an increased or decreased cardiovascular (CV) risk [6,7,8,9,10].…”