Antibodies of IgM subclass to phosphorylcholine and oxidized LDL are protective factors for atherosclerosis in patients with hypertension

Sawada, Jun; Georgiades, Anastasia; Wu, Ruihua; Thulin, Thomas; Fairé, Ulf dé; Frostegård, Johan

doi:10.1016/j.atherosclerosis.2005.10.017

Cited by 155 publications

(164 citation statements)

References 38 publications

Supporting

Mentioning

142

Contrasting

Unclassified

Order By: Relevance

“…Mice immunized with Streptococcus pneumoniae produce antibodies (predominantly of the IgM isotype) that appear to cross-react with PC in oxLDL [75,77]. The proposed protective role of IgM antibodies in relation to the development of atherosclerosis in humans has been previously discussed in this review, and remains hypothetical, given the contradictory results reported by different groups [15,[80][81][82]90].…”

Section: The Role Of Phospholipid Antibodies In Atherosclerosismentioning

confidence: 99%

“…However, a recent report on the effects of pneumococcal vaccination in humans failed to demonstrate the induction of circulating IgM antibodies to oxLDL [79]. Nevertheless, a protective role of IgM antibodies to modified forms of LDL has also been proposed in humans, based on a negative correlation between IgM MDA-LDL antibody levels and carotid intima-media thickness [80,81]. The sum of published data, however, is contradictory.…”

Section: Are Igm Antibodies To Modified Ldl Protective?mentioning

confidence: 99%

“…Other types of phospholipid antibodies react with phosporylcholine (PC) [81] and lysophosphatidylcholine (LPC) [86], formed during LDL oxidation. These antibodies are detected using cardiolipin [89] or commercial preparations of PC complexed with bovine serum albumin [81], and the reaction of patient's sera with this substrate cab be inhibited by oxLDL.…”

Section: The Role Of Phospholipid Antibodies In Atherosclerosismentioning

confidence: 99%

“…These antibodies are detected using cardiolipin [89] or commercial preparations of PC complexed with bovine serum albumin [81], and the reaction of patient's sera with this substrate cab be inhibited by oxLDL. The phospholipid antibodies detected by these methods seem to be predominantly of the IgM isotype [81,89] and it has been postulated that they recognize PC epitopes shared by Streptococcus pneumoniae. Mice immunized with Streptococcus pneumoniae produce antibodies (predominantly of the IgM isotype) that appear to cross-react with PC in oxLDL [75,77].…”

Section: The Role Of Phospholipid Antibodies In Atherosclerosismentioning

confidence: 99%

See 3 more Smart Citations

Atherogenesis and the humoral immune response to modified lipoproteins

Virella¹,

Lopes‐Virella²

2008

Atherosclerosis

View full text Add to dashboard Cite

Modified forms of LDL are immunogenic and activate both cell-mediated and humoral immune responses. Both types of responses are pro-inflammatory and are probably primary players in the perpetuation of the chronic inflammatory reaction characteristic of atherosclerosis. The immunologic response to modified LDL can be directed to MHC-II-associated peptides in the case of T helper cells, and to a variety of epitopes -modified lysine groups, modified phospholipids, proteins that become associated with oxidized LDL (such as β2GP1) -in the case of B cell responses. T cell activation is likely to play a major role through cross-activation of macrophages. Humoral responses to modified LDL are pathogenic as a consequence of the formation of antigen-antibody complexes containing modified LDL and IgG antibodies. Those immune complexes induce cholesterol ester accumulation in macrophages and macrophage-like cells, and induce the release of proinflammatory cytokines, chemokines, oxygen active radicals, and matrix metalloproteinases from those cells. There is no conclusive evidence supporting a protective role for IgM antibodies in humans, possibly because autoantibodies to modified lipoproteins are predominantly of the IgG isotype.

show abstract

Section: The Role Of Phospholipid Antibodies In Atherosclerosismentioning

confidence: 99%

Section: Are Igm Antibodies To Modified Ldl Protective?mentioning

confidence: 99%

Section: The Role Of Phospholipid Antibodies In Atherosclerosismentioning

confidence: 99%

Section: The Role Of Phospholipid Antibodies In Atherosclerosismentioning

confidence: 99%

See 2 more Smart Citations

Atherogenesis and the humoral immune response to modified lipoproteins

Virella¹,

Lopes‐Virella²

2008

Atherosclerosis

View full text Add to dashboard Cite

show abstract

“…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).…”

Section: P Hosphorylcholine (Pc) Is a Classic T-independent Ag That Imentioning

confidence: 99%

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

Fiskesund

Stéen

Amara

et al. 2014

The Journal of Immunology

Self Cite

View full text Add to dashboard Cite

Phosphorylcholine (PC) is a classic T-independent Ag that is exposed on apoptotic cells, oxidized phospholipids, and bacterial polysaccharides. Experimental as well as epidemiological studies have over the past decade implicated Abs against PC (anti-PC) as anti-inflammatory and a strong protective factor in cardiovascular disease. Although clinically important, little is known about the development of anti-PC in humans. This study was conceived to dissect the human anti-PC repertoire and generate human mAbs. We designed a PC-specific probe to identify, isolate, and characterize PC-reactive B cells from 10 healthy individuals. The donors had all mounted somatically mutated Abs toward PC using a broad variety of Ig genes. PC-reactive B cells were primarily found in the IgM+ memory subset, although significant numbers also were detected among naive, IgG+, and CD27+CD43+ B cells. Abs from these subsets were clonally related, suggesting a common origin. mAbs derived from the same donors exhibited equivalent or higher affinity for PC than the well-characterized murine T-15 clone. These results provide novel insights into the cellular and molecular ontogeny of atheroprotective PC Abs, thereby offering new opportunities for Ab-based therapeutic interventions.

show abstract

Natural Antibodies

Zouali¹

2009

Encyclopedia of Life Sciences

View full text Add to dashboard Cite

Natural antibodies are essentially antibodies of the immunoglobulin M (IgM) isotype present in the circulation of normal humans and other mammalian species that have not been previously exposed to deliberate immunization. They are often directed against highly conserved epitopes and often bind to ligands of varying chemical composition with low affinity. This antibody subset contrasts with immune antibodies, which are produced in response to the introduction of antigen to the immune system. Natural antibodies are frequently directed to intracellular structures, rather than to cell‐surface antigens. They have been found to play a role in protection against infectious agents and to exert homeostatic functions. Other investigations suggest that natural antibodies might play a pathogenic role. Key concepts A natural antibody is an antibody present in the circulation of an animal or a subject that had not been previously exposed to the corresponding antigen. Certain B‐lymphocyte subsets, such as B‐1a cells, are committed to natural antibody production. The antibody repertoire expressed in B‐cell malignancies exhibits several features in common with those of the natural antibody repertoire of healthy subjects. It is possible that natural antibody production is driven by microorganisms indigenous to the organism, such as bacteria living in the intestine. Natural antibodies play a role in shaping the B‐cell repertoire and may represent the precursors of antibodies to pathogens. Natural antibodies could serve as innate recognition receptors, recognizing various bacterial cell wall components or parasites. Studies of rodents rendered deficient in natural antibodies suggest that this antibody subset is endowed with a homeostatic potential and housekeeping functions, such as recognition and removal of senescent cells and other self‐antigens. Circumstantial evidence suggests that natural antibodies can be associated with protection against Alzheimer disease, atherosclerosis or cancer development. B lymphocytes secreting natural antibodies could represent a reservoir capable of mutating their immunoglobulin variable region genes to give rise to high‐affinity pathogenic autoantibodies.

show abstract

Antibodies of IgM subclass to phosphorylcholine and oxidized LDL are protective factors for atherosclerosis in patients with hypertension

Cited by 155 publications

References 38 publications

Atherogenesis and the humoral immune response to modified lipoproteins

Atherogenesis and the humoral immune response to modified lipoproteins

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

Natural Antibodies

Contact Info

Product

Resources

About