IgM phosphorylcholine antibodies inhibit cell death and constitute a strong protection marker for atherosclerosis development, particularly in combination with other auto-antibodies against modified LDL

Fiskesund, Roland; Sawada, Jun; Bulatović, Ivana; Vikström, Max; Fairé, Ulf dé; Frostegård, Johan

doi:10.1016/j.rinim.2012.01.001

Cited by 41 publications

(63 citation statements)

References 34 publications

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“…Moreover, cross-sectional studies have shown that higher concentrations of circulating IgM anti-PC in lupus are associated with a lower probability of a cardiovascular event, such as a myocardial infarction or stroke [84, 89] and lower prevalence of atherosclerotic plaques in the carotids [94]. In non-autoimmune patients, prospective screening has demonstrated that levels IgM anti-PC may provide a biomarker for prediction of preclinical cardiovascular disease associated with atherosclerotic plaque burden as measured by ultrasound intima-media thickness [95, 96]. Retrospective studies have also suggested that lower baseline levels of IgM anti-PC may be predictive for stroke [97, 98], myocardial infarction [99] or overall atherosclerotic cardiovascular disease incidence [100].…”

Section: Protective Natural Igm In Clinical Surveysmentioning

confidence: 99%

“…However, a recent report found that the anti-carbohydrate antibodies in pooled IgG in intravenous immunoglobulin (IVIG) preparations are not restricted to IgG2 but can be associated with other subclasses as well [110]. IgG of different subclasses may convey functional differences, and it may therefore be relevant that a recent clinical survey found correlative evidence that IgG1 anti-PC levels are more strongly associated with protective properties in atherosclerosis than IgG2 [95]. This topic remains controversial, in part because they will require characterization of the fine specificity and functional properties of monoclonal anti-PC antibodies in the context of different subclasses.…”

Section: Natural Igg Antibodiesmentioning

confidence: 99%

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Natural IgM: Beneficial Autoantibodies for the Control of Inflammatory and Autoimmune Disease

2014

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Natural IgM are highly represented in the circulation at birth, and these often autoreactive antibodies have been postulated to have innate-like properties and play crucial roles in apoptotic cell clearance, tissue homeostasis, and immune modulation. This review summarizes the known properties of these IgM autoantibodies, and the evidence that these anti-apoptotic cell IgM natural antibodies can regulate inflammatory responses through ancient pathways of the innate immune system that first arose long before the initial emergence of the adaptive immune system. While the regulatory contributions of these natural IgM autoantibodies are certainly not an essential and fundamental component of host defenses, these provide an additional layer to further protect the host. More importantly, these IgM antibody responses are highly inducible and their up-regulation can be a powerful means for the host to survive in a setting of chronic inflammation. The observed beneficial clinical associations for cardiovascular disease and autoimmunity, as well as opportunities for potential therapeutic implications are discussed.

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Section: Protective Natural Igm In Clinical Surveysmentioning

confidence: 99%

Section: Natural Igg Antibodiesmentioning

confidence: 99%

Natural IgM: Beneficial Autoantibodies for the Control of Inflammatory and Autoimmune Disease

2014

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“…Human anti-PC could be anti-atherogenic and decrease risk of CVD by anti-inflammatory effects (107), inhibition of oxLDL-uptake through scavenger receptors (111) and inhibition of LPC-induced cell (112). In mouse models, the anti-inflammatory effect of anti-PC was confirmed, and facilitating phagocytosis was reported as one mechanism.…”

Section: Diabetes and Causes Of Immune Activation In Atherosclerosismentioning

confidence: 99%

“…This is supported by clinical studies, animal and in vitro experiments (50). As discussed, mechanisms include anti-inflammatory (107, 167), inhibition of cell death (112), and decreased uptake of oxLDL in macrophages (105). Further, administration of immunoglobulins has shown promising results in animal studies (168).…”

Section: Treatment Against Inflammation and Immune Activation To Amelmentioning

confidence: 99%

Immune Mechanisms in Atherosclerosis, Especially in Diabetes Type 2

Frostegård

2013

Front. Endocrinol.

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Atherosclerosis and ensuing cardiovascular disease (CVD) are major complications of diabetes type 2. Atherosclerosis is a chronic inflammatory condition involving immunocompetent cells of different types present in the lesions. Even though inflammation and immune activation may be more pronounced in atherosclerosis in diabetes type 2, there does not appear to be any major differences between diabetics and non-diabetics. Similar factors are thus implicated in atherosclerosis-associated immune activation in both groups. The cause of immune activation is not known and different mutually non-exclusive possibilities exist. Oxidized and/or enzymatically modified forms of low-density lipoprotein (OxLDL) and dead cells are present in atherosclerotic plaques. OxLDL could play a role, being pro-inflammatory and immunostimulatory as it activates T-cells and is cytotoxic at higher concentrations. Inflammatory phospholipids in OxLDL are implicated, with phosphorylcholine (PC) as one of the exposed antigens. Antibodies against PC (anti-PC) are anti-atherogenic in mouse studies, and anti-PC is negatively associated with development of atherosclerosis and CVD in humans. Bacteria and virus have been discussed as potential causes of immune activation, but it has been difficult to find direct evidence supporting this hypothesis, and antibiotic trials in humans have been negative or inconclusive. Heat shock proteins (HSP) could be one major target for atherogenic immune reactions. More direct causes of plaque rupture include cytokines such as interleukin 1β (IL-1β), tumor necrosis factor (TNF), and also lipid mediators as leukotrienes. In addition, in diabetes, hyperglycemia and oxidative stress appear to accelerate the development of atherosclerosis, one mechanism could be via promotion of immune reactions. To prove that immune reactions are causative of atherosclerosis and CVD, further studies with immune-modulatory treatments are needed.

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“…Mechanisms by which human anti-PC could ameliorate atherosclerosis and CVD include: anti-inflammatory effects, inhibition of pro-inflammatory effects by inflammatory phospholipids [42], inhibition of uptake of oxLDL through scavenger receptors [43] and inhibition of cell death induced by LPC, a major inflammatory phospholipid [44]. In another paper, the inflammatory effect of anti-PC is also confirmed in a mouse model, in which facilitating phagocytosis is described as one mechanism.…”

Section: Introductionmentioning

confidence: 99%

Immunity, atherosclerosis and cardiovascular disease

Frostegård

2013

BMC Med

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Atherosclerosis, the major cause of cardiovascular disease (CVD), is a chronic inflammatory condition with immune competent cells in lesions producing mainly pro-inflammatory cytokines. Dead cells and oxidized forms of low density lipoproteins (oxLDL) are abundant. The major direct cause of CVD appears to be rupture of atherosclerotic plaques. oxLDL has proinflammatory and immune-stimulatory properties, causes cell death at higher concentrations and contains inflammatory phospholipids with phosphorylcholine (PC) as an interesting epitope. Antibodies against PC (anti-PC) may be atheroprotective, one mechanism being anti-inflammatory. Bacteria and virus have been discussed, but it has been difficult to find direct evidence, and antibiotic trials have not been successful. Heat shock proteins could be one major target for atherogenic immune reactions. More direct causes of plaque rupture include pro-inflammatory cytokines, chemokines, and lipid mediators. To prove that inflammation is a cause of atherosclerosis and CVD, clinical studies with anti-inflammatory and/or immune-modulatory treatment are needed. The potential causes of immune reactions and inflammation in atherosclerosis and how inflammation can be targeted therapeutically to provide novel treatments for CVD are reviewed.

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IgM phosphorylcholine antibodies inhibit cell death and constitute a strong protection marker for atherosclerosis development, particularly in combination with other auto-antibodies against modified LDL

Abstract: Group I anti-PC antibodies, particularly of the IgM class, are independent protection markers for atherosclerosis progression. One potential mechanism of action is inhibition of LPC-induced cell cytotoxicity.

Cited by 41 publications

References 34 publications

Natural IgM: Beneficial Autoantibodies for the Control of Inflammatory and Autoimmune Disease

Natural IgM: Beneficial Autoantibodies for the Control of Inflammatory and Autoimmune Disease

Immune Mechanisms in Atherosclerosis, Especially in Diabetes Type 2

Immunity, atherosclerosis and cardiovascular disease

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