Serum Immunoglobulin M Concentration Varies With Triglyceride Levels In An Adult Population: Tianjin Chronic Low-grade Systemic Inflammation And Health(TCLSIHealth) Cohort Study

Background:Obesity,which is increasing globally at an alarming rate,is a major risk factor for chronic diseases, including metabolic syndrome(MS), type 2 diabetes(T2D), cardiovascular disease(CVD), and certain forms of cancer. Autoimmunity is correlated with increased levels of chronic low-grade inflammation,and immunoglobulin M(IgM) is reactive to autoantigens and believed to be important for autoimmunity. Recent studies have suggested that the increase of IgM antibodies was associated with antigen exposure caused by obesity IgM is the first class of antibodies produced during a primary antibody response,and is predominantly produced by B-1 cells. In the absence of stimulation by specific antigens, IgM is polyreactive not only to foreign antigens but also to phylogenetically conserved autoantigens, including nucleic acids, heat shock proteins, carbohydrates, and phospholipids.Moreover, since IgM has a relatively low affinity for modified self-components, it is believed to be important for progression of autoimmunity. Triglyceride(TG) is fatty acid carrier and initiator of oxidative stress, and it has been hypothesized that TG stimulates B cells to secrete IgM.Objective:Few studies have investigated the relationship between TG and IgM in human populations. We designed a cross-sectional and prospective cohort study to evaluate how serum TG levels are related to IgM concentration.Method:Participants were recruited from Tianjin Medical University General Hospital-Health Management Centre. The TCLSIHealth data from 2010 to 2013 was used in this study. Both a baseline cross-sectional(n = 10,808) and a prospective assessment(n = 2,615) were performed. Participants whom body mass index(BMI) or high density lipoprotein cholesterol(HDL) or low density lipoprotein cholesterol(LDL) measurement were not available were excluded(n = 47). We excluded those with a history of Hyperlipidemia(n = 13) or CVD(n = 657) or cancer(n = 108) or hepatic disease(n = 75). Owing to these exclusions, the final cross-sectional study population comprised 10,808 participants(median(interquartile range, IQR) age: 46.0(39.0, 54.0) years; male: 60.0%). For follow-up analysis, participants were excluded at baseline if they had received a health examination only in 2013(n = 7,356). The participants for whom BMI measurements were not available during follow-up were also excluded(n = 3). Following the exclusion, the final cohort study population comprised 2,615 participants(follow-up rate: 75.8%; mean(IQR) age: 45.0(39.0, 52.0) years; male: 65.4%).All statistical analyses were performed using the Statistical Analysis System version 9.3 for Windows(SAS Institute Inc., Cary, NC, USA). Because their IgM serum concentration was significantly different, males and females were analyzed separately in this study. For baseline characteristics analysis, the differences among TG categories were examined using analysis of variance for continuous variables and multiple logistic regression analysis for proportional variables. Bonferroni-corrected P values were used for comparisons between TG quartiles. Analysis of covariance was used to examine relationships between quartiles of TG, and the level of IgM after adjustment for covariates:age, baseline BMI, SCr, ALB, hypertension, diabetes, smoking status, drinking status, and family history of CVD, hypertension, hyperlipidemia, and diabetes. The multiple linear regression analysis was used to examine the relationships between the change of TG and the change of IgM with adjustment for the covariates mentioned above. All tests were two tailed and P <0.05 was defined as statistically significant.Result:After multiple adjustments for confounding factors, serum IgM level in the highest quartile of TG in males was significantly higher than levels in lower quartiles(P <0.05). There was no significant difference between the four quartiles in females(P = 0.91). In follow-up analysis, a multiple linear regression model showed a significant and positive correlation between changes in IgM levels and changes of TG concentration in males(P = 0.04, standard coefficient = 0.882).Conclusion:This cross-sectional and prospective cohort study is the first to show that serum concentration of IgM varies with serum TG levels in males, but not in females. The findings suggest that IgM may be involved in the pathological process of lipid metabolism disorder. Further research is needed to explore the mechanism by which TG leads to increased IgM concentration.