Abstract
BackgroundInflammatory cytokines contribute to the development of atherosclerosis. Natural antibodies in the circulation have protective effects on common diseases including atherosclerosis-related conditions.PurposeThe present study aimed to investigate the possible involvement of circulating IgG antibodies against inflammatory cytokines in atherosclerosis.MethodsA 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.ResultsAtherosclerotic patients had an increase in the levels of circulating IgG to TNFα-1(adjusted r2 = 0.038, p < 0.001) and IL1α (adjusted r2 = 0.025, p = 0.002) compared with control subjects. Female patients mainly contributed to increased anti-TNFα-1 IgG levels (adjusted r2 = 0.073, p < 0.001) and anti-IL1α IgG levels (adjusted r2 = 0.044, p = 0.003). In addition, female patients showed higher anti-IL1β-2 IgG levels than controls (adjusted r2 = 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.ConclusionNatural antibodies to inflammatory cytokines may be potential biomarkers for atherosclerosis.
Highlights
Atherosclerosis, the most common cause of cardiovascular diseases, is a chronic and systemic inflammatory disorder mainly affecting the intima of large and medium-sized arteries [1]
All coefficient of variation (CV) calculated with specific binding ratio (SBR) of the quality control (QC) sample was less than 20% (Table 3), suggesting a good reproducibility for the in-house enzyme-linked immunosorbent assay (ELISA)
Patients with atherosclerosis had a significantly higher level of circulating immunoglobulin G (IgG) against Interleukin 1α (IL1α) antigens than control subjects (t = 3.084, p = 0.002) and female patients mainly contributed to the significant change (t = 2.964, p = 0.003)
Summary
Atherosclerosis, the most common cause of cardiovascular diseases, is a chronic and systemic inflammatory disorder mainly affecting the intima of large and medium-sized arteries [1]. Several risk factors are likely to be responsible for the development of atherosclerosis, such as smoking, diabetes mellitus, abdominal obesity, atherogenic dyslipidemia and hypertension [2, 3]. It has long disease latency and frequently coexists in > 1 vascular bed [4]. An increase in circulating levels of certain immunoglobulin G (IgG) has been identified in patients with atherosclerosis-related diseases. 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
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