Association of Circulating IgE and CML levels With in-Stent Restenosis After Drug-Eluting Stent Implantation in Type 2 Diabetic Patients With Stable Coronary Artery Disease

Background: We investigated whether serum levels of immunoglobin (Ig) E and Nε-carboxymethyl-lysine (CML) are related to in-stent restenosis (ISR) in patients with stable coronary artery disease and type 2 diabetes mellitus (T2DM).Methods: Serum levels of IgE and CML were measured in 416 stable angina patients with T2DM who received angiographic follow-up 12 months after percutaneous coronary intervention (PCI) with third-generation drug-eluting stent (DES) implantation for de novo lesions. Multivariate logistic regression analysis was performed to assess the association between IgE or CML and ISR. In mice models, femoral artery injury was induced in mice receiving albumin or glycated albumin injection, and immunofluorescence staining of the injured artery segment was performed 4 weeks later using CML and IgE antibodies. Results: Both IgE and CML levels were higher in patients with ISR (n=196) compared with non-ISR patients (n=220). The rate of ISR increased stepwise with increasing tertiles of IgE and CML levels, and IgE correlated significantly with CML. After adjusting for potential confounders, IgE and CML levels remained independently associated with ISR. IgE and CML levels improved the predictive capability of traditional risk factors for ISR, and there existed an interaction between IgE and CML in relation to ISR (P for interaction < 0.01). In mice models, glycated albumin induced increased CML and IgE infiltration in the injured femoral artery segment which was associated with a higher degree of neointimal hyperplasia and luminal stenosis.Conclusion: Elevated circulating IgE and CML levels confer an increased risk for ISR after DES-based PCI in type 2 diabetic patients with stable coronary artery disease.