{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,19]],"date-time":"2026-05-19T23:25:05Z","timestamp":1779233105079,"version":"3.51.4"},"reference-count":133,"publisher":"MDPI AG","issue":"6","license":[{"start":{"date-parts":[[2023,6,1]],"date-time":"2023-06-01T00:00:00Z","timestamp":1685577600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Swedish Heart and Lung Association"},{"name":"Swedish Rheumatism Association"},{"name":"King Gustav V\u2019s Birthday Fund"},{"name":"Intricare"},{"name":"Preciseads"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Metabolites"],"abstract":"<jats:p>Atherosclerosis and its main consequence, cardiovascular disease (CVD) are nowadays regarded as chronic inflammatory disease conditions, and CVD is the main cause of death in the world. Other examples of chronic inflammation are rheumatic and other autoimmune conditions, but also diabetes, obesity, and even osteoarthritis among others. In addition, infectious diseases can have traits in common with these conditions. Systemic lupus erythematosus (SLE) is a prototypical autoimmune disease, where atherosclerosis is increased and the risk of CVD is very high. This is a clinical problem but could also shed light on the role of the immune system in atherosclerosis and CVD. Underlying mechanisms are of major interest and these are only partially known. Phosphorylcholine (PC) is a small lipid-related antigen, which is both a danger associated molecular pattern (DAMP), and a pathogen associated molecular pattern (PAMP). Antibodies against PC are ubiquitous and 5\u201310% of circulating IgM is IgM anti-PC. Anti-PC, especially IgM and IgG1 anti-PC, has been associated with protection in the chronic inflammatory conditions mentioned above, and develops during the first years of life, while being present at very low levels at birth. Animal experiments with immunization to raise anti-PC ameliorate atherosclerosis and other chronic inflammatory conditions. Potential mechanisms include anti-inflammatory, immune modulatory, clearance of dead cells and protection against infectious agents. An intriguing possibility is to raise anti-PC levels through immunization, to prevent and\/or ameliorate chronic inflammation.<\/jats:p>","DOI":"10.3390\/metabo13060720","type":"journal-article","created":{"date-parts":[[2023,6,2]],"date-time":"2023-06-02T02:16:48Z","timestamp":1685672208000},"page":"720","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":12,"title":["Antibodies against Phosphorylcholine\u2014Implications for Chronic Inflammatory Diseases"],"prefix":"10.3390","volume":"13","author":[{"given":"Johan","family":"Frosteg\u00e5rd","sequence":"first","affiliation":[{"name":"IMM, Nobels V\u00e4g 13, Karolinska Institutet, 17165 Stockholm, Sweden"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2023,6,1]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Frostegard, J. (2013). Immunity, atherosclerosis and cardiovascular disease. BMC Med., 11.","DOI":"10.1186\/1741-7015-11-117"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"33","DOI":"10.1016\/S0021-9150(99)00011-8","article-title":"Cytokine expression in advanced human atherosclerotic plaques: Dominance of pro-inflammatory (Th1) and macrophage-stimulating cytokines","volume":"145","author":"Frostegard","year":"1999","journal-title":"Atherosclerosis"},{"key":"ref_3","first-page":"915","article-title":"Beyond cholesterol. Modifications of low-density lipoprotein that increase its atherogenicity [see comments]","volume":"320","author":"Steinberg","year":"1989","journal-title":"N. Engl. J. Med."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"96","DOI":"10.1007\/s00428-006-0176-7","article-title":"Atherosclerosis research from past to present--on the track of two pathologists with opposing views, Carl von Rokitansky and Rudolf Virchow","volume":"449","author":"Mayerl","year":"2006","journal-title":"Virchows Arch."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"1119","DOI":"10.1056\/NEJMoa1707914","article-title":"Antiinflammatory Therapy with Canakinumab for Atherosclerotic Disease","volume":"377","author":"Ridker","year":"2017","journal-title":"N. Engl. J. Med."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"2497","DOI":"10.1056\/NEJMoa1912388","article-title":"Efficacy and Safety of Low-Dose Colchicine after Myocardial Infarction","volume":"381","author":"Tardif","year":"2019","journal-title":"N. Engl. J. Med."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"197","DOI":"10.1161\/ATVBAHA.114.304342","article-title":"Induction of dendritic cell-mediated T-cell activation by modified but not native low-density lipoprotein in humans and inhibition by annexin a5: Involvement of heat shock proteins","volume":"35","author":"Liu","year":"2015","journal-title":"Arterioscler. Thromb. Vasc. Biol."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"778","DOI":"10.1161\/CIRCRESAHA.111.256859","article-title":"Role of phospholipid oxidation products in atherosclerosis","volume":"111","author":"Lee","year":"2012","journal-title":"Circ. Res."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"2230","DOI":"10.1194\/jlr.M800174-JLR200","article-title":"A novel function of lipoprotein [a] as a preferential carrier of oxidized phospholipids in human plasma","volume":"49","author":"Bergmark","year":"2008","journal-title":"J. Lipid Res."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"192","DOI":"10.1002\/art.20780","article-title":"Lipid peroxidation is enhanced in patients with systemic lupus erythematosus and is associated with arterial and renal disease manifestations","volume":"52","author":"Frostegard","year":"2005","journal-title":"Arthritis Rheum."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"1887","DOI":"10.1161\/hc4101.097518","article-title":"Risk factors for cardiovascular disease in systemic lupus erythematosus","volume":"104","author":"Svenungsson","year":"2001","journal-title":"Circulation"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"3284","DOI":"10.1096\/fj.09-146852","article-title":"Phospholipolyzed LDL induces an inflammatory response in endothelial cells through endoplasmic reticulum stress signaling","volume":"24","author":"Gora","year":"2010","journal-title":"Faseb J."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"426","DOI":"10.1097\/MOL.0b013e328364e85a","article-title":"Oxidation-specific epitopes as targets for biotheranostic applications in humans: Biomarkers, molecular imaging and therapeutics","volume":"24","author":"Miller","year":"2013","journal-title":"Curr. Opin. Lipidol."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"301","DOI":"10.1038\/s41586-018-0198-8","article-title":"Oxidized phospholipids are proinflammatory and proatherogenic in hypercholesterolaemic mice","volume":"558","author":"Que","year":"2018","journal-title":"Nature"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"29","DOI":"10.1038\/291029a0","article-title":"IgG antibodies to phosphorylcholine exhibit more diversity than their IgM counterparts","volume":"291","author":"Gearhart","year":"1981","journal-title":"Nature"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"1177","DOI":"10.1084\/jem.156.4.1177","article-title":"Anti-phosphorylcholine antibodies of the T15 idiotype are optimally protective against Streptococcus pneumoniae","volume":"156","author":"Briles","year":"1982","journal-title":"J. Exp. Med."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"993","DOI":"10.1128\/iai.39.2.993-999.1983","article-title":"Protection against pneumococcal infection in mice conferred by phosphocholine-binding antibodies: Specificity of the phosphocholine binding and relation to several types","volume":"39","author":"Szu","year":"1983","journal-title":"Infect. Immun."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"6490","DOI":"10.1016\/j.vaccine.2007.06.034","article-title":"Purification and structure characterization of the active component in the pneumococcal 22F polysaccharide capsule used for adsorption in pneumococcal enzyme-linked immunosorbent assays","volume":"25","author":"Skovsted","year":"2007","journal-title":"Vaccine"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"45","DOI":"10.2174\/187153012799278893","article-title":"Immunomodulatory properties of ES-62, a phosphorylcholine-containing glycoprotein secreted by Acanthocheilonema viteae","volume":"12","author":"Harnett","year":"2012","journal-title":"Endocr. Metab. Immune Disord. Drug Targets"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"637","DOI":"10.1002\/eji.1830040914","article-title":"Phosphorylcholine-bearing components in homogenates of nematodes","volume":"4","author":"Pery","year":"1974","journal-title":"Eur. J. Immunol."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"101","DOI":"10.1016\/j.molbiopara.2008.06.014","article-title":"The PCome of Caenorhabditis elegans as a prototypic model system for parasitic nematodes: Identification of phosphorylcholine-substituted proteins","volume":"161","author":"Grabitzki","year":"2008","journal-title":"Mol. Biochem. Parasitol."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"883","DOI":"10.1016\/0140-6736(92)90926-T","article-title":"Autoantibody against oxidised LDL and progression of carotid atherosclerosis","volume":"339","author":"Salonen","year":"1992","journal-title":"Lancet"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"441","DOI":"10.1161\/01.ATV.15.4.441","article-title":"Patients with early-onset peripheral vascular disease have increased levels of autoantibodies against oxidized LDL","volume":"15","author":"Bergmark","year":"1995","journal-title":"Arterioscler. Thromb. Vasc. Biol."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"2605","DOI":"10.1001\/archinte.1994.00420220105012","article-title":"Antibody against oxidized low-density lipoprotein predicting myocardial infarction","volume":"154","author":"Puurunen","year":"1994","journal-title":"Arch. Intern. Med."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"3159","DOI":"10.1161\/01.ATV.17.11.3159","article-title":"Antibodies against cardiolipin and oxidatively modified LDL in 50-year-old men predict myocardial infarction","volume":"17","author":"Wu","year":"1997","journal-title":"Arterioscler. Thromb. Vasc. Biol."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"23","DOI":"10.1161\/01.ATV.19.1.23","article-title":"Autoantibodies against oxidized low density lipoprotein in patients with angiographically verified coronary artery disease","volume":"19","author":"Lehtimaki","year":"1999","journal-title":"Arterioscler. Thromb. Vasc. Biol."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"53","DOI":"10.1161\/01.HYP.33.1.53","article-title":"Autoantibodies to OxLDL are decreased in individuals with borderline hypertension","volume":"33","author":"Wu","year":"1999","journal-title":"Hypertension"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"923","DOI":"10.1016\/0140-6736(93)91213-6","article-title":"Crossreaction between antibodies to oxidised low-density lipoprotein and to cardiolipin in systemic lupus erythematosus","volume":"341","author":"Vaarala","year":"1993","journal-title":"Lancet"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"160","DOI":"10.1016\/j.atherosclerosis.2005.10.017","article-title":"Antibodies of IgM subclass to phosphorylcholine and oxidized LDL are protective factors for atherosclerosis in patients with hypertension","volume":"188","author":"Su","year":"2006","journal-title":"Atherosclerosis"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"310","DOI":"10.1007\/s11239-013-0968-y","article-title":"Autoantibodies to phosphorylcholine and cardiovascular outcomes in patients with acute coronary syndromes in the ATLAS ACS-TIMI 46 trial","volume":"37","author":"Geller","year":"2014","journal-title":"J. Thromb. Thrombolysis"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"394","DOI":"10.1016\/j.atherosclerosis.2014.07.030","article-title":"Low levels of IgM antibodies against phosphorylcholine are associated with fast carotid intima media thickness progression and cardiovascular risk in men","volume":"236","author":"Gigante","year":"2014","journal-title":"Atherosclerosis"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"27","DOI":"10.1016\/j.imlet.2015.12.009","article-title":"Aberrant levels of natural IgM antibodies in osteoarthritis and rheumatoid arthritis patients in comparison to healthy controls","volume":"170","author":"Nguyen","year":"2016","journal-title":"Immunol. Lett."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"686","DOI":"10.1111\/eci.12457","article-title":"Phosphorylcholine antibodies are diminished in ANCA-associated vasculitis","volume":"45","author":"Wilde","year":"2015","journal-title":"Eur. J. Clin. Investig."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"111S","DOI":"10.1177\/0003489419835568","article-title":"Role of Phosphorylcholine-Specific Immunoglobulin M in Acute Upper Respiratory Tract Infections","volume":"128","author":"Ohori","year":"2019","journal-title":"Ann. Otol. Rhinol. Laryngol."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"R214","DOI":"10.1186\/ar3193","article-title":"Increased prevalence of vulnerable atherosclerotic plaques and low levels of natural IgM antibodies against phosphorylcholine in patients with systemic lupus erythematosus","volume":"12","author":"Anania","year":"2010","journal-title":"Arthritis Res. Ther."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"344","DOI":"10.1002\/acr2.11127","article-title":"Immunoglobulin G1 Antibodies Against Phosphorylcholine Are Associated with Protection in Systemic Lupus Erythematosus and Atherosclerosis: Potential Underlying Mechanisms","volume":"2","author":"Thiagarajan","year":"2020","journal-title":"ACR Open Rheumatol."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"11010","DOI":"10.1038\/s41598-020-66981-z","article-title":"IgM antibodies against malondialdehyde and phosphorylcholine in different systemic rheumatic diseases","volume":"10","author":"Thiagarajan","year":"2020","journal-title":"Sci. Rep."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"390","DOI":"10.1016\/j.clim.2012.01.002","article-title":"IgM autoantibodies to distinct apoptosis-associated antigens correlate with protection from cardiovascular events and renal disease in patients with SLE","volume":"142","author":"Gronwall","year":"2012","journal-title":"Clin. Immunol."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"13","DOI":"10.1007\/s00392-014-0750-y","article-title":"Low levels of natural IgM antibodies against phosphorylcholine are independently associated with vascular remodeling in patients with coronary artery disease","volume":"104","author":"Gleissner","year":"2015","journal-title":"Clin. Res. Cardiol. Off. J. Ger. Card. Soc."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"414","DOI":"10.1016\/j.atherosclerosis.2015.10.024","article-title":"Long-term prognostic value of IgM antibodies against phosphorylcholine for adverse cardiovascular events in patients with stable coronary heart disease","volume":"243","author":"Imhof","year":"2015","journal-title":"Atherosclerosis"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"259","DOI":"10.1016\/j.ejvs.2018.09.010","article-title":"Anti-phosphorylcholine IgM, an Anti-inflammatory Mediator, Predicts Peripheral Vein Graft Failure: A Prospective Observational Study","volume":"57","author":"Sobel","year":"2019","journal-title":"Eur. J. Vasc. Endovasc. Surg."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"1102","DOI":"10.1093\/cvr\/cvx112","article-title":"A role for autoantibodies in atherogenesis","volume":"113","author":"Iseme","year":"2017","journal-title":"Cardiovasc. Res."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"31","DOI":"10.1111\/jth.13874","article-title":"Natural antibodies to oxidation-specific epitopes: Innate immune response and venous thromboembolic disease","volume":"16","author":"Eichinger","year":"2018","journal-title":"J. Thromb. Haemost."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"3388","DOI":"10.1002\/art.34537","article-title":"Natural antibody to apoptotic cell membranes inhibits the proinflammatory properties of lupus autoantibody immune complexes","volume":"64","author":"Vas","year":"2012","journal-title":"Arthritis Rheum."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"408","DOI":"10.1093\/oxfordjournals.aje.a009122","article-title":"Age-specific incidence rates of myocardial infarction and angina in women with systemic lupus erythematosus: Comparison with the Framingham Study","volume":"145","author":"Manzi","year":"1997","journal-title":"Am. J. Epidemiol."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"48","DOI":"10.1111\/joim.13557","article-title":"Systemic lupus erythematosus and cardiovascular disease","volume":"293","author":"Frostegard","year":"2023","journal-title":"J. Intern. Med."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"663","DOI":"10.1016\/S0002-9149(00)01453-3","article-title":"Prevalence and relation to risk factors of carotid atherosclerosis and left ventricular hypertrophy in systemic lupus erythematosus and antiphospholipid antibody syndrome","volume":"87","author":"Roman","year":"2001","journal-title":"Am. J. Cardiol."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"2399","DOI":"10.1056\/NEJMoa035471","article-title":"Prevalence and correlates of accelerated atherosclerosis in systemic lupus erythematosus","volume":"349","author":"Roman","year":"2003","journal-title":"N. Engl. J. Med."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"2401","DOI":"10.1212\/01.wnl.0000314697.76580.cb","article-title":"Identifying vulnerable carotid plaques by noninvasive imaging","volume":"70","author":"Kwee","year":"2008","journal-title":"Neurology"},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"2171","DOI":"10.1161\/01.CIR.103.17.2171","article-title":"Echolucent plaques are associated with high risk of ischemic cerebrovascular events in carotid stenosis: The tromso study","volume":"103","author":"Mathiesen","year":"2001","journal-title":"Circulation"},{"key":"ref_51","doi-asserted-by":"crossref","unstructured":"Waliszewska-Prosol, M., and Ejma, M. (2022). Hashimoto Encephalopathy-Still More Questions than Answers. Cells., 11.","DOI":"10.3390\/cells11182873"},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"809007","DOI":"10.3389\/fcvm.2022.809007","article-title":"Antibodies against Phosphorylcholine Among 60-Year-Olds: Clinical Role and Simulated Interactions","volume":"9","author":"Samal","year":"2022","journal-title":"Front. Cardiovasc. Med."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"94","DOI":"10.1111\/cei.13441","article-title":"Different subclasses and isotypes of antibodies against phosphorylcholine in haemodialysis patients: Association with mortality","volume":"201","author":"Samal","year":"2020","journal-title":"Clin. Exp. Immunol."},{"key":"ref_54","first-page":"241","article-title":"Human-igg subclasses and their relation to carbohydrate antigen immunocompetence","volume":"5","author":"Scott","year":"1988","journal-title":"Diagn. Clin. Immunol."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"1254","DOI":"10.1086\/424517","article-title":"Cross-reactivity of human immunoglobulin G2 recognizing phosphorylcholine and evidence for protection against major bacterial pathogens of the human respiratory tract","volume":"190","author":"Goldenberg","year":"2004","journal-title":"J. Infect. Dis."},{"key":"ref_56","first-page":"197","article-title":"Periodontal diseases and cardiovascular events: Meta-analysis of observational studies","volume":"59","author":"Blaizot","year":"2009","journal-title":"Int. Dent. J."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"4814","DOI":"10.1128\/IAI.67.9.4814-4818.1999","article-title":"Antiphosphorylcholine antibody levels are elevated in humans with periodontal diseases","volume":"67","author":"Schenkein","year":"1999","journal-title":"Infect. Immun."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"2109","DOI":"10.1073\/pnas.73.6.2109","article-title":"Size differences among immunoglobulin heavy chains from phosphorylcholine-binding proteins","volume":"73","author":"Rudikoff","year":"1976","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"4551","DOI":"10.4049\/jimmunol.1303035","article-title":"Naturally occurring human phosphorylcholine antibodies are predominantly products of affinity-matured B cells in the adult","volume":"192","author":"Fiskesund","year":"2014","journal-title":"J. Immunol."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"2109","DOI":"10.4049\/jimmunol.2000437","article-title":"Antibodies against Phosphorylcholine and Malondialdehyde during the First Two Years of Life","volume":"205","author":"Thiagarajan","year":"2020","journal-title":"J. Immunol."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"12120","DOI":"10.1038\/s41598-021-91679-1","article-title":"Potential natural immunization against atherosclerosis in hibernating bears","volume":"11","author":"Samal","year":"2021","journal-title":"Sci. Rep."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"1809","DOI":"10.1093\/hmg\/ddy094","article-title":"A genome-wide association study of IgM antibody against phosphorylcholine: Shared genetics and phenotypic relationship to chronic lymphocytic leukemia","volume":"27","author":"Chen","year":"2018","journal-title":"Hum. Mol. Genet."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"1945","DOI":"10.1093\/rheumatology\/kex260","article-title":"The worldwide incidence and prevalence of systemic lupus erythematosus: A systematic review of epidemiological studies","volume":"56","author":"Rees","year":"2017","journal-title":"Rheumatology"},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"2344","DOI":"10.1016\/S0140-6736(19)30546-X","article-title":"Novel paradigms in systemic lupus erythematosus","volume":"393","author":"Dorner","year":"2019","journal-title":"Lancet"},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"2009","DOI":"10.1136\/annrheumdis-2017-211663","article-title":"Survival in adults and children with systemic lupus erythematosus: A systematic review and Bayesian meta-analysis of studies from 1950 to 2016","volume":"76","author":"Tektonidou","year":"2017","journal-title":"Ann. Rheum. Dis."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"1400","DOI":"10.1002\/art.40930","article-title":"2019 European League Against Rheumatism\/American College of Rheumatology Classification Criteria for Systemic Lupus Erythematosus","volume":"71","author":"Aringer","year":"2019","journal-title":"Arthritis Rheumatol."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"3638562","DOI":"10.1155\/2019\/3638562","article-title":"Programmed Cell Death Pathways in the Pathogenesis of Systemic Lupus Erythematosus","volume":"2019","author":"Yang","year":"2019","journal-title":"J. Immunol. Res."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"2888","DOI":"10.1002\/art.11237","article-title":"Increased apoptotic neutrophils and macrophages and impaired macrophage phagocytic clearance of apoptotic neutrophils in systemic lupus erythematosus","volume":"48","author":"Ren","year":"2003","journal-title":"Arthritis Rheum."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"8392","DOI":"10.4049\/jimmunol.175.12.8392","article-title":"Global natural regulatory T cell depletion in active systemic lupus erythematosus","volume":"175","author":"Miyara","year":"2005","journal-title":"J. Immunol."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"610","DOI":"10.3389\/fimmu.2015.00610","article-title":"Disturbed T Cell Signaling and Altered Th17 and Regulatory T Cell Subsets in the Pathogenesis of Systemic Lupus Erythematosus","volume":"6","author":"Rother","year":"2015","journal-title":"Front. Immunol."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"36","DOI":"10.1016\/j.atherosclerosis.2017.11.010","article-title":"IgM antibodies against phosphorylcholine promote polarization of T regulatory cells from patients with atherosclerotic plaques, systemic lupus erythematosus and healthy donors","volume":"268","author":"Sun","year":"2018","journal-title":"Atherosclerosis"},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"87","DOI":"10.1016\/j.coi.2020.10.014","article-title":"Type I interferon in the pathogenesis of systemic lupus erythematosus","volume":"67","author":"Postal","year":"2020","journal-title":"Curr. Opin. Immunol."},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"1540","DOI":"10.1126\/science.1064890","article-title":"Induction of dendritic cell differentiation by IFN-alpha in systemic lupus erythematosus","volume":"294","author":"Blanco","year":"2001","journal-title":"Science"},{"key":"ref_74","first-page":"73ra20","article-title":"Netting neutrophils are major inducers of type I IFN production in pediatric systemic lupus erythematosus","volume":"3","author":"Caielli","year":"2011","journal-title":"Sci. Transl. Med."},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"125","DOI":"10.1016\/j.jaut.2015.08.004","article-title":"Immunogenetics of systemic lupus erythematosus: A comprehensive review","volume":"64","author":"Niewold","year":"2015","journal-title":"J. Autoimmun."},{"key":"ref_76","unstructured":"Ha, E., Bae, S.C., and Kim, K. (2021). Seminars in Immunopathology, Springer."},{"key":"ref_77","doi-asserted-by":"crossref","unstructured":"Kwon, Y.C., Chun, S., Kim, K., and Mak, A. (2019). Update on the Genetics of Systemic Lupus Erythematosus: Genome-Wide Association Studies and Beyond. Cells, 8.","DOI":"10.3390\/cells8101180"},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"772","DOI":"10.1038\/s41467-021-21049-y","article-title":"Identification of 38 novel loci for systemic lupus erythematosus and genetic heterogeneity between ancestral groups","volume":"12","author":"Wang","year":"2021","journal-title":"Nat. Commun."},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"799788","DOI":"10.3389\/fimmu.2021.799788","article-title":"Gut Microbiota Dysbiosis in Systemic Lupus Erythematosus: Novel Insights into Mechanisms and Promising Therapeutic Strategies","volume":"12","author":"Pan","year":"2021","journal-title":"Front. Immunol."},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"727","DOI":"10.1177\/0961203315627202","article-title":"Overall and cause-specific mortality in systemic lupus erythematosus: An updated meta-analysis","volume":"25","author":"Lee","year":"2016","journal-title":"Lupus"},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"515","DOI":"10.1038\/s41584-021-00668-1","article-title":"Global epidemiology of systemic lupus erythematosus","volume":"17","author":"Barber","year":"2021","journal-title":"Nat. Rev. Rheumatol."},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"144","DOI":"10.1097\/BOR.0000000000000480","article-title":"Epidemiology of systemic lupus erythematosus: An update","volume":"30","author":"Stojan","year":"2018","journal-title":"Curr. Opin. Rheumatol."},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"799","DOI":"10.1080\/1744666X.2017.1327352","article-title":"Epidemiology of systemic lupus erythematosus","volume":"13","author":"Alarcon","year":"2017","journal-title":"Expert Rev. Clin. Immunol."},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"605","DOI":"10.1038\/nrrheum.2016.137","article-title":"The global burden of SLE: Prevalence, health disparities and socioeconomic impact","volume":"12","author":"Carter","year":"2016","journal-title":"Nat. Rev. Rheumatol."},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"221","DOI":"10.1016\/0002-9343(76)90431-9","article-title":"The bimodal mortality pattern of systemic lupus erythematosus","volume":"60","author":"Urowitz","year":"1976","journal-title":"Am. J. Med."},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"216","DOI":"10.1097\/00005792-199207000-00004","article-title":"Cardiovascular Disease in Systemic Lupus Erythematosus, A Study of 75 Patients from a Defined Population","volume":"71","author":"Sturfelt","year":"1992","journal-title":"Medicine"},{"key":"ref_87","first-page":"713","article-title":"Cardiovascular disease a hazard despite improved prognosis in patients with systemic lupus erythematosus: Results from a Swedish population based study 1964\u201395","volume":"31","author":"Bjornadal","year":"2004","journal-title":"J. Rheumatol."},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"1120","DOI":"10.1016\/S0140-6736(96)03032-2","article-title":"Plasma homocysteine as a risk factor for atherothrombotic events in systemic lupus erythematosus","volume":"348","author":"Petri","year":"1996","journal-title":"Lancet"},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"513","DOI":"10.1016\/0002-9343(92)90578-Y","article-title":"Risk Factors for coronary Artery Disease in Patients with Systemic Lupus Erythematosus","volume":"93","author":"Petri","year":"1992","journal-title":"Am. J. Med."},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"321","DOI":"10.1136\/ard.59.5.321","article-title":"Inflammation-mediated rheumatic diseases and atherosclerosis","volume":"59","author":"Manzi","year":"2000","journal-title":"Ann. Rheum. Dis."},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"57","DOI":"10.1001\/archinte.1995.00430010063008","article-title":"Risk factors that attenuate the female coronary disease advantage","volume":"155","author":"Kannel","year":"1995","journal-title":"Arch. Intern. Med."},{"key":"ref_92","doi-asserted-by":"crossref","first-page":"2331","DOI":"10.1002\/1529-0131(200110)44:10<2331::AID-ART395>3.0.CO;2-I","article-title":"Traditional Framingham risk factors fail to fully account for accelerated atherosclerosis in systemic lupus erythematosus","volume":"44","author":"Esdaile","year":"2001","journal-title":"Arthritis Rheum."},{"key":"ref_93","doi-asserted-by":"crossref","first-page":"243","DOI":"10.1016\/0002-9343(75)90575-6","article-title":"The Heart in Systemic Lupus Erythematosus and the changes Induced in it by Corticosteroid Therapy","volume":"58","author":"Bulkeley","year":"1975","journal-title":"Am. J. Med."},{"key":"ref_94","doi-asserted-by":"crossref","first-page":"385","DOI":"10.1212\/WNL.44.3_Part_1.385","article-title":"Large cerebral vessel occlusive disease in systemic lupus erythematosus","volume":"44","author":"Mitsias","year":"1994","journal-title":"Neurology"},{"key":"ref_95","doi-asserted-by":"crossref","first-page":"e1183","DOI":"10.1097\/MD.0000000000001183","article-title":"Cardiovascular Events in Systemic Lupus Erythematosus: A Nationwide Study in Spain From the RELESSER Registry","volume":"94","author":"Blanco","year":"2015","journal-title":"Medicine"},{"key":"ref_96","first-page":"709","article-title":"The risk of cardiovascular morbidity and cardiovascular mortality in systemic lupus erythematosus and lupus nephritis: A Danish nationwide population-based cohort study","volume":"56","author":"Hermansen","year":"2017","journal-title":"Rheumatology"},{"key":"ref_97","doi-asserted-by":"crossref","first-page":"1355","DOI":"10.1093\/rheumatology\/kez456","article-title":"Outcomes of acute cardiovascular events in rheumatoid arthritis and systemic lupus erythematosus: A population-based study","volume":"59","author":"Lai","year":"2020","journal-title":"Rheumatology"},{"key":"ref_98","doi-asserted-by":"crossref","first-page":"3789","DOI":"10.1093\/rheumatology\/keaa862","article-title":"Comparative risks of cardiovascular disease events among SLE patients receiving immunosuppressive medications","volume":"60","author":"Choi","year":"2021","journal-title":"Rheumatology"},{"key":"ref_99","doi-asserted-by":"crossref","first-page":"1431","DOI":"10.1002\/acr.24328","article-title":"Comparative Risks of Cardiovascular Disease in Patients With Systemic Lupus Erythematosus, Diabetes Mellitus, and in General Medicaid Recipients","volume":"72","author":"Barbhaiya","year":"2020","journal-title":"Arthritis Care Res."},{"key":"ref_100","doi-asserted-by":"crossref","first-page":"317","DOI":"10.1177\/0961203319826672","article-title":"Systemic lupus erythematosus is a risk factor for cancer: A nationwide population-based study in Korea","volume":"28","author":"Bae","year":"2019","journal-title":"Lupus"},{"key":"ref_101","doi-asserted-by":"crossref","first-page":"1841","DOI":"10.3899\/jrheum.161121","article-title":"Evolution of Risk Factors for Atherosclerotic Cardiovascular Events in Systemic Lupus Erythematosus: A Longterm Prospective Study","volume":"44","author":"Tselios","year":"2017","journal-title":"J. Rheumatol."},{"key":"ref_102","doi-asserted-by":"crossref","first-page":"1544","DOI":"10.1136\/annrheumdis-2016-210973","article-title":"Stroke in systemic lupus erythematosus: A Swedish population-based cohort study","volume":"76","author":"Arkema","year":"2017","journal-title":"Ann. Rheum. Dis."},{"key":"ref_103","doi-asserted-by":"crossref","first-page":"459","DOI":"10.1007\/s12026-016-8884-9","article-title":"Association between ischemic heart disease and systemic lupus erythematosus-a large case-control study","volume":"65","author":"Watad","year":"2017","journal-title":"Immunol. Res."},{"key":"ref_104","doi-asserted-by":"crossref","first-page":"107466","DOI":"10.1016\/j.intimp.2021.107466","article-title":"Patients with systemic lupus erythematosus face a high risk of cardiovascular disease: A systematic review and Meta-analysis","volume":"94","author":"Lu","year":"2021","journal-title":"Int. Immunopharmacol."},{"key":"ref_105","doi-asserted-by":"crossref","first-page":"211","DOI":"10.1097\/BOR.0000000000000773","article-title":"The latest in systemic lupus erythematosus-accelerated atherosclerosis: Related mechanisms inform assessment and therapy","volume":"33","author":"Appleton","year":"2021","journal-title":"Curr. Opin. Rheumatol."},{"key":"ref_106","doi-asserted-by":"crossref","first-page":"110","DOI":"10.1016\/j.clim.2018.02.014","article-title":"Contribution of MTHFR gene variants in lupus related subclinical atherosclerosis","volume":"193","author":"Giannelou","year":"2018","journal-title":"Clin. Immunol."},{"key":"ref_107","doi-asserted-by":"crossref","first-page":"532","DOI":"10.1111\/jth.14385","article-title":"Human low-affinity IgG receptor FcgammaRIIA polymorphism H131R associates with subclinical atherosclerosis and increased platelet activity in systemic lupus erythematosus","volume":"17","author":"Clancy","year":"2019","journal-title":"J. Thromb. Haemost."},{"key":"ref_108","doi-asserted-by":"crossref","first-page":"1025","DOI":"10.1016\/j.amjcard.2013.05.040","article-title":"Relation of carotid intima-media thickness and plaque with incident cardiovascular events in women with systemic lupus erythematosus","volume":"112","author":"Kao","year":"2013","journal-title":"Am. J. Cardiol."},{"key":"ref_109","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.ijcard.2018.06.010","article-title":"Subclinical atherosclerosis in asymptomatic carriers of persistent antiphospholipid antibodies positivity: A cross-sectional study","volume":"274","author":"Emmi","year":"2019","journal-title":"Int. J. Cardiol."},{"key":"ref_110","doi-asserted-by":"crossref","first-page":"1063","DOI":"10.1136\/annrheumdis-2017-212614","article-title":"Novel gene variants associated with cardiovascular disease in systemic lupus erythematosus and rheumatoid arthritis","volume":"77","author":"Leonard","year":"2018","journal-title":"Ann. Rheum. Dis."},{"key":"ref_111","doi-asserted-by":"crossref","first-page":"1071","DOI":"10.1136\/ard.62.11.1071","article-title":"Risk factors for subclinical atherosclerosis in a prospective cohort of patients with systemic lupus erythematosus","volume":"62","author":"Doria","year":"2003","journal-title":"Ann. Rheum. Dis."},{"key":"ref_112","doi-asserted-by":"crossref","first-page":"220","DOI":"10.1191\/096120399678847597","article-title":"Atherosclerosis-related markers in systemic lupus erythematosus patients: The role of humoral immunity in enhanced atherogenesis","volume":"8","author":"George","year":"1999","journal-title":"Lupus"},{"key":"ref_113","doi-asserted-by":"crossref","first-page":"232","DOI":"10.1016\/j.atherosclerosis.2011.12.026","article-title":"Correlation of peripheral Th17 cells and Th17-associated cytokines to the severity of carotid artery plaque and its clinical implication","volume":"221","author":"Liu","year":"2012","journal-title":"Atherosclerosis"},{"key":"ref_114","doi-asserted-by":"crossref","first-page":"125","DOI":"10.1007\/s00395-010-0135-y","article-title":"Expression of IL-17A in human atherosclerotic lesions is associated with increased inflammation and plaque vulnerability","volume":"106","author":"Erbel","year":"2011","journal-title":"Basic Res. Cardiol."},{"key":"ref_115","doi-asserted-by":"crossref","first-page":"280","DOI":"10.1161\/ATVBAHA.114.303568","article-title":"Treating atherosclerosis with regulatory T cells","volume":"35","author":"Foks","year":"2015","journal-title":"Arterioscler. Thromb. Vasc. Biol."},{"key":"ref_116","doi-asserted-by":"crossref","first-page":"344","DOI":"10.1002\/eji.201344280","article-title":"Regulatory T cells in systemic lupus erythematosus","volume":"45","author":"Ohl","year":"2015","journal-title":"Eur. J. Immunol."},{"key":"ref_117","doi-asserted-by":"crossref","first-page":"330","DOI":"10.1038\/ni904","article-title":"Foxp3 programs the development and function of CD4+CD25+ regulatory T cells","volume":"4","author":"Fontenot","year":"2003","journal-title":"Nat. Immunol."},{"key":"ref_118","doi-asserted-by":"crossref","first-page":"283","DOI":"10.1038\/nri3823","article-title":"The promise of low-dose interleukin-2 therapy for autoimmune and inflammatory diseases","volume":"15","author":"Klatzmann","year":"2015","journal-title":"Nat. Rev. Immunol."},{"key":"ref_119","doi-asserted-by":"crossref","first-page":"540","DOI":"10.1016\/j.jacc.2006.11.054","article-title":"Phosphorylcholine-targeting immunization reduces atherosclerosis","volume":"50","author":"Caligiuri","year":"2007","journal-title":"J. Am. Coll. Cardiol."},{"key":"ref_120","doi-asserted-by":"crossref","first-page":"736","DOI":"10.1038\/nm876","article-title":"Pneumococcal vaccination decreases atherosclerotic lesion formation: Molecular mimicry between Streptococcus pneumoniae and oxidized LDL","volume":"9","author":"Binder","year":"2003","journal-title":"Nat. Med."},{"key":"ref_121","doi-asserted-by":"crossref","first-page":"1116","DOI":"10.1016\/j.vaccine.2022.01.027","article-title":"A nasal double DNA adjuvant system induces atheroprotective IgM antibodies via dendritic cell-B-1a B cell interactions","volume":"40","author":"Yoshimatsu","year":"2022","journal-title":"Vaccine"},{"key":"ref_122","doi-asserted-by":"crossref","first-page":"83","DOI":"10.1016\/j.atherosclerosis.2005.11.033","article-title":"Passive immunization with monoclonal IgM antibodies against phosphorylcholine reduces accelerated vein graft atherosclerosis in apolipoprotein E-null mice","volume":"189","author":"Chyu","year":"2006","journal-title":"Atherosclerosis"},{"key":"ref_123","doi-asserted-by":"crossref","first-page":"1228","DOI":"10.1016\/j.jacbts.2020.09.012","article-title":"Phosphorylcholine Antibodies Preserve Cardiac Function and Reduce Infarct Size by Attenuating the Post-Ischemic Inflammatory Response","volume":"5","author":"Pluijmert","year":"2020","journal-title":"JACC Basic Transl. Sci."},{"key":"ref_124","doi-asserted-by":"crossref","first-page":"1346","DOI":"10.4049\/jimmunol.0900948","article-title":"Regulation of dendritic cells and macrophages by an anti-apoptotic cell natural antibody that suppresses TLR responses and inhibits inflammatory arthritis","volume":"183","author":"Chen","year":"2009","journal-title":"J. Immunol."},{"key":"ref_125","doi-asserted-by":"crossref","first-page":"203","DOI":"10.1016\/j.ijpara.2014.12.006","article-title":"The immunomodulatory parasitic worm product ES-62 reduces lupus-associated accelerated atherosclerosis in a mouse model","volume":"45","author":"Aprahamian","year":"2015","journal-title":"Int. J. Parasitol."},{"key":"ref_126","doi-asserted-by":"crossref","first-page":"1144","DOI":"10.1093\/rheumatology\/ken120","article-title":"Natural antibodies against phosphorylcholine as potential protective factors in SLE","volume":"47","author":"Su","year":"2008","journal-title":"Rheumatology"},{"key":"ref_127","doi-asserted-by":"crossref","first-page":"73","DOI":"10.1016\/j.jaut.2009.05.003","article-title":"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","volume":"34","author":"Su","year":"2010","journal-title":"J. Autoimmun."},{"key":"ref_128","doi-asserted-by":"crossref","first-page":"27","DOI":"10.1016\/j.clim.2016.04.007","article-title":"IgM antibodies against malondialdehyde and phosphorylcholine are together strong protection markers for atherosclerosis in systemic lupus erythematosus: Regulation and underlying mechanisms","volume":"166\u2013167","author":"Rahman","year":"2016","journal-title":"Clin. Immunol."},{"key":"ref_129","doi-asserted-by":"crossref","first-page":"845","DOI":"10.1093\/ajcn\/66.4.845","article-title":"Age relations of cardiovascular risk factors in a traditional Melanesian society: The Kitava Study","volume":"66","author":"Lindeberg","year":"1997","journal-title":"Am. J. Clin. Nutr."},{"key":"ref_130","doi-asserted-by":"crossref","first-page":"1259","DOI":"10.1136\/bmj.299.6710.1259","article-title":"Hay fever, hygiene, and household size","volume":"299","author":"Strachan","year":"1989","journal-title":"BMJ"},{"key":"ref_131","doi-asserted-by":"crossref","first-page":"337","DOI":"10.1097\/00130832-200310000-00003","article-title":"Innate immune responses to mycobacteria and the downregulation of atopic responses","volume":"3","author":"Rook","year":"2003","journal-title":"Curr. Opin. Allergy Clin. Immunol."},{"key":"ref_132","doi-asserted-by":"crossref","first-page":"5","DOI":"10.1007\/s12016-011-8285-8","article-title":"Hygiene hypothesis and autoimmune diseases","volume":"42","author":"Rook","year":"2012","journal-title":"Clin. Rev. Allergy Immunol."},{"key":"ref_133","doi-asserted-by":"crossref","unstructured":"Versini, M., Jeandel, P.Y., Bashi, T., Bizzaro, G., Blank, M., and Shoenfeld, Y. (2015). Unraveling the Hygiene Hypothesis of helminthes and autoimmunity: Origins, pathophysiology, and clinical applications. BMC Med., 13.","DOI":"10.1186\/s12916-015-0306-7"}],"container-title":["Metabolites"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2218-1989\/13\/6\/720\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T19:47:16Z","timestamp":1760125636000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2218-1989\/13\/6\/720"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,6,1]]},"references-count":133,"journal-issue":{"issue":"6","published-online":{"date-parts":[[2023,6]]}},"alternative-id":["metabo13060720"],"URL":"https:\/\/doi.org\/10.3390\/metabo13060720","relation":{},"ISSN":["2218-1989"],"issn-type":[{"value":"2218-1989","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,6,1]]}}}