Serum Immunoglobulin M Concentration Is Positively Related to Metabolic Syndrome in an Adult Population: Tianjin Chronic Low-Grade Systemic Inflammation and Health (TCLSIH) Cohort Study
Persistent low-grade systemic inflammation has been increasingly recognized as a common pathological process, and an important contributing factor to cardiovascular diseases and its risk factor, metabolic syndrome. Immunoglobulin M is reactive to multiple autoantigens and is inferred to be important for autoimmunity, implying that immunoglobulin M may be a potential risk factor for metabolic syndrome. However, few epidemiological studies are available which are related to this potential link. Therefore, we designed a cross-sectional study of 9,379 subjects to evaluate the relationship between immunoglobulin M and metabolic syndrome in an adult population. Subjects who received health examinations were recruited from the Tianjin Medical University General Hospital-Health Management Center in Tianjin, China. Immunoglobulin M was determined with an immunonephelometric technique. Metabolic syndrome was defined according to the criteria of the American Heart Association scientific statements of 2009. Multiple logistic regression analysis was used to examine the relationships between the quartiles of immunoglobulin M and the prevalence of metabolic syndrome. After adjustment for covariates, the odds ratio of having metabolic syndrome in the fourth quartile compared with the first quartile of immunoglobulin M was 1.19 times for males (95% confidence interval, 1.002–1.41) and 1.39 times for females (95% confidence interval, 1.07–1.80). Immunoglobulin M levels also showed positive relationships with the ratio of elevated triglycerides and reduced high-density lipoprotein cholesterol in males. The study is the first to show that immunoglobulin M is independently related to metabolic syndrome and its individual components (elevated triglycerides and reduced high-density lipoprotein cholesterol) in males, whereas immunoglobulin M is independently related to metabolic syndrome in females but not to its individual components. Further studies are needed to explore the causality and the exact role of immunoglobulin M in metabolic syndrome.
References
[1]
Lozano R, Naghavi M, Foreman K, Lim S, Shibuya K, et al. (2012) Global and regional mortality from 235 causes of death for 20 age groups in 1990 and 2010: a systematic analysis for the Global Burden of Disease Study 2010. Lancet 380: 2095–2128.
Pearson TA, Mensah GA, Alexander RW, Anderson JL, Cannon RO 3rd, et al. (2003) Markers of inflammation and cardiovascular disease: application to clinical and public health practice: A statement for healthcare professionals from the Centers for Disease Control and Prevention and the American Heart Association. Circulation 107: 499–511. doi: 10.1161/01.cir.0000052939.59093.45
[4]
Jenny NS (2012) Inflammation in aging: cause, effect, or both? Discov Med 13: 451–460.
[5]
Kamp DW, Shacter E, Weitzman SA (2011) Chronic inflammation and cancer: the role of the mitochondria. Oncology (Williston Park) 25: : 400–410, 413.
[6]
Romeo GR, Lee J, Shoelson SE (2012) Metabolic syndrome, insulin resistance, and roles of inflammation—mechanisms and therapeutic targets. Arterioscler Thromb Vasc Biol 32: 1771–1776. doi: 10.1161/atvbaha.111.241869
[7]
Nathan C (2008) Epidemic inflammation: pondering obesity. Mol Med 14: 485–492.
[8]
Calabro P, Golia E, Maddaloni V, Malvezzi M, Casillo B, et al. (2009) Adipose tissue-mediated inflammation: the missing link between obesity and cardiovascular disease? Intern Emerg Med 4: 25–34. doi: 10.1007/s11739-008-0207-2
[9]
Nikolopoulou A, Kadoglou NP (2012) Obesity and metabolic syndrome as related to cardiovascular disease. Expert Rev Cardiovasc Ther 10: 933–939. doi: 10.1586/erc.12.74
[10]
Sun S, Ji Y, Kersten S, Qi L (2012) Mechanisms of inflammatory responses in obese adipose tissue. Annu Rev Nutr 32: 261–286. doi: 10.1146/annurev-nutr-071811-150623
[11]
Marti A, Marcos A, Martinez JA (2001) Obesity and immune function relationships. Obes Rev 2: 131–140. doi: 10.1046/j.1467-789x.2001.00025.x
[12]
Sell H, Eckel J (2010) Adipose tissue inflammation: novel insight into the role of macrophages and lymphocytes. Curr Opin Clin Nutr Metab Care 13: 366–370. doi: 10.1097/mco.0b013e32833aab7f
[13]
Winer DA, Winer S, Shen L, Wadia PP, Yantha J, et al. (2011) B cells promote insulin resistance through modulation of T cells and production of pathogenic IgG antibodies. Nat Med 17: 610–617. doi: 10.1038/nm.2353
[14]
Arai S, Maehara N, Iwamura Y, Honda S, Nakashima K, et al. (2013) Obesity-associated autoantibody production requires AIM to retain the immunoglobulin M immune complex on follicular dendritic cells. Cell Rep 3: 1187–1198. doi: 10.1016/j.celrep.2013.03.006
[15]
Ehrenstein MR, Notley CA (2010) The importance of natural IgM: scavenger, protector and regulator. Nat Rev Immunol 10: 778–786. doi: 10.1038/nri2849
[16]
Vollmers HP, Brandlein S (2006) Natural IgM antibodies: the orphaned molecules in immune surveillance. Adv Drug Deliv Rev 58: 755–765. doi: 10.1016/j.addr.2005.08.007
[17]
Duarte-Rey C, Bogdanos DP, Leung PS, Anaya JM, Gershwin ME (2012) IgM predominance in autoimmune disease: genetics and gender. Autoimmun Rev 11: A404–412. doi: 10.1016/j.autrev.2011.12.001
[18]
Marchalonis JJ, Schluter SF, Wilson L, Yocum DE, Boyer JT, et al. (1993) Natural human antibodies to synthetic peptide autoantigens: correlations with age and autoimmune disease. Gerontology 39: 65–79. doi: 10.1159/000213517
[19]
Licata G, Argano C, Di Chiara T, Parrinello G, Scaglione R (2006) Obesity: a main factor of metabolic syndrome? Panminerva Med 48: 77–85.
[20]
Shirai K (2004) Obesity as the core of the metabolic syndrome and the management of coronary heart disease. Curr Med Res Opin 20: 295–304. doi: 10.1185/030079903125003008
[21]
Gonzalez-Quintela A, Alende R, Gude F, Campos J, Rey J, et al. (2008) Serum levels of immunoglobulins (IgG, IgA, IgM) in a general adult population and their relationship with alcohol consumption, smoking and common metabolic abnormalities. Clin Exp Immunol 151: 42–50. doi: 10.1111/j.1365-2249.2007.03545.x
[22]
Tianjin Municipal Government (2007) About Tianjin. Available: http://www.tj.gov.cn/english/About_tianj?in/Visiting_Tianjin/. Accessed 2013 Aug 5.
[23]
Alberti KG, Eckel RH, Grundy SM, Zimmet PZ, Cleeman JI, et al. (2009) Harmonizing the metabolic syndrome: a joint interim statement of the International Diabetes Federation Task Force on Epidemiology and Prevention; National Heart, Lung, and Blood Institute; American Heart Association; World Heart Federation; International Atherosclerosis Society; and International Association for the Study of Obesity. Circulation 120: 1640–1645. doi: 10.1161/circulationaha.109.192644
[24]
Marzullo P, Minocci A, Giarda P, Marconi C, Tagliaferri A, et al. (2013) Lymphocytes and immunoglobulin patterns across the threshold of severe obesity. Endocrine.
[25]
Xu H, Barnes GT, Yang Q, Tan G, Yang D, et al. (2003) Chronic inflammation in fat plays a crucial role in the development of obesity-related insulin resistance. J Clin Invest 112: 1821–1830. doi: 10.1172/jci19451
[26]
Shi H, Kokoeva MV, Inouye K, Tzameli I, Yin H, et al. (2006) TLR4 links innate immunity and fatty acid-induced insulin resistance. J Clin Invest 116: 3015–3025. doi: 10.1172/jci28898
[27]
Kovanen PT, Manttari M, Palosuo T, Manninen V, Aho K (1998) Prediction of myocardial infarction in dyslipidemic men by elevated levels of immunoglobulin classes A, E, and G, but not M. Arch Intern Med 158: 1434–1439. doi: 10.1001/archinte.158.13.1434
[28]
Bouman A, Heineman MJ, Faas MM (2005) Sex hormones and the immune response in humans. Hum Reprod Update 11: 411–423. doi: 10.1093/humupd/dmi008
[29]
Kolovou GD, Anagnostopoulou KK, Salpea KD, Mikhailidis DP (2007) The prevalence of metabolic syndrome in various populations. Am J Med Sci 333: 362–371. doi: 10.1097/maj.0b013e318065c3a1
[30]
Gleicher N, Barad DH (2007) Gender as risk factor for autoimmune diseases. J Autoimmun 28: 1–6. doi: 10.1016/j.jaut.2006.12.004
[31]
Ortona E, Margutti P, Matarrese P, Franconi F, Malorni W (2008) Redox state, cell death and autoimmune diseases: a gender perspective. Autoimmun Rev 7: 579–584. doi: 10.1016/j.autrev.2008.06.001
[32]
Knudsen GP (2009) Gender bias in autoimmune diseases: X chromosome inactivation in women with multiple sclerosis. J Neurol Sci 286: 43–46.
[33]
Maury E, Brichard SM (2010) Adipokine dysregulation, adipose tissue inflammation and metabolic syndrome. Mol Cell Endocrinol 314: 1–16. doi: 10.1016/j.mce.2009.07.031
[34]
Elks CM, Francis J (2010) Central adiposity, systemic inflammation, and the metabolic syndrome. Curr Hypertens Rep 12: 99–104. doi: 10.1007/s11906-010-0096-4
[35]
Suganami T, Tanimoto-Koyama K, Nishida J, Itoh M, Yuan X, et al. (2007) Role of the Toll-like receptor 4/NF-kappaB pathway in saturated fatty acid-induced inflammatory changes in the interaction between adipocytes and macrophages. Arterioscler Thromb Vasc Biol 27: 84–91. doi: 10.1161/01.atv.0000251608.09329.9a