Low levels of IgM antibodies to phosphorylcholine predict cardiovascular disease in 60-year old men: Effects on uptake of oxidized LDL in macrophages as a potential mechanism

Naturally Occurring Human Phosphorylcholine Antibodies Are Predominantly Products of Affinity-Matured B Cells in the Adult

“…Subsequent research has demonstrated that anti-PC aids in clearance of apoptotic cells (6,30) and prevents the formation of pathogenic foam cells in atherosclerosis by clearing oxidized low density lipoprotein (1). Murine studies with PC vaccination have shown strong beneficial effects on experimental atherosclerosis in vivo (11)(12)(13), and human epidemiology has consistently linked anti-PC insufficiency to cardiovascular events (14)(15)(16)(17). These findings in combination with earlier knowledge on the presence of T15 B cells in germ-free mice (20) has led to the formulation of a hypothesis that germlineencoded PC-reactive Abs produced by innate B1 cells fulfill an important housekeeping function in human physiology (8,10).…”

“…Although our data does not preclude the possibility of germline encoded innate anti-PC in humans, it seems clear that in adults, if present, this putative innate response is overshadowed by an adaptive thymus independent-process mediated by conventional B cells. Innate or not, this is still a clinically relevant immune response, and multiple studies have consistently confirmed that having a low titer of anti-PC is an independent risk factor for cardiovascular disease (14)(15)(16)(17).…”

“…These results have lead scientists to hypothesize that anti-PC has an important housekeeping function in homeostasis (8)(9)(10). This understanding has been further cemented by animal studies (11)(12)(13) and several large epidemiological studies (14)(15)(16)(17), which have consistently demonstrated that humans with low levels of anti-PC are at elevated risk of cardiovascular disease. Furthermore, high levels of anti-PC are negatively associated with atherosclerosis development in humans (18).…”

B Cells Producing Pathogenic Autoantibodies

“…In addition, T15 IgM blocks the binding of OxLDL to scavenger receptors on macrophages, thereby inhibiting inflammatory responses mediated by macrophages after activation by oxidized phospholipids [14][15][16]. Considering that the accumulation of apoptotic cells and oxidized lipoproteins is key to the pathogenesis of atherosclerosis, T15 IgM antibodies are thought to mediate protection against atherogenesis [17,18]. Moreover, engagement of Clq by IgM immune complexes, including T15 immune complexes, leads to activation of LAIR-1, an inhibitory molecule on myeloid cells, thereby helping to maintain myeloid cells in a quiescent state [19,20].…”

Inflammatory mediators after endovascular aortic aneurysm repair

“…IgM anti-PC, on the other hand, are natural antibodies against oxidised low-density lipoprotein (oxLDL), an important mediator in the development of atherosclerosis and atherogenesis [22]. Low levels of IgM anti-PC are associated with an increased risk of atherosclerotic cardiovascular disease [23][24][25], but the marker has not yet been evaluated in patients with AAA.…”