Circulating natural antibodies to inflammatory cytokines are potential biomarkers for atherosclerosis

Background Inflammatory cytokines contribute to the development of atherosclerosis. Natural antibodies in the circulation have protective effects on common diseases including atherosclerosis-related conditions. Purpose The present study aimed to investigate the possible involvement of circulating IgG antibodies against inflammatory cytokines in atherosclerosis. Methods A total of 220 patients with diagnosis of atherosclerosis and 200 healthy controls were recruited. Seven linear peptide antigens were used to develop an enzyme-linked immunosorbent assay in-house for detection of plasma IgG antibodies against interleukin 1β (fragments IL1β-1 and IL1β-2), IL6, IL8, tumor necrosis factor alpha (fragments TNFα-1 and TNFα-2) and IL1α. Results Atherosclerotic patients had an increase in the levels of circulating IgG to TNFα-1(adjusted r 2 = 0.038, p < 0.001) and IL1α (adjusted r 2 = 0.025, p = 0.002) compared with control subjects. Female patients mainly contributed to increased anti-TNFα-1 IgG levels (adjusted r 2 = 0.073, p < 0.001) and anti-IL1α IgG levels (adjusted r 2 = 0.044, p = 0.003). In addition, female patients showed higher anti-IL1β-2 IgG levels than controls (adjusted r 2 = 0.023, p = 0.026). There was no significant change of circulating IgG antibodies to other cytokines. ROC curve analysis showed an AUC of 0.564 for anti-TNFα-1 IgG assay with 22.8% sensitivity against a specificity of 90.0%, and an AUC of 0.539 for anti-IL1α IgG assay with 17.8% sensitivity against a specificity of 90.0%; the anti-IL1β-2 IgG assay had an AUC of 0.580 with 26.3% sensitivity against a specificity of 89.8% in female patients. There was no correlation between plasma IgG levels and carotid intima-media thickness. Conclusion Natural antibodies to inflammatory cytokines may be potential biomarkers for atherosclerosis.