Cardiac antibody production to self-antigens in children and adolescents during and following the correction of severe diabetic ketoacidosis

Abstract

Diabetic cardiomyopathy (DC) is an independent phenotype of diabetic cardiovascular disease. The understanding of the pathogenesis of DC in young patients with type 1 diabetes (T1D) is limited. The cardiac insults of diabetic ketoacidosis (DKA) and progression of DC could include development of antibodies (Abs) to cardiac self-antigens (SAgs) such as: myosin (M), vimentin (V) and k-alpha 1 tubulin (Kα1T). The goal of this study is to determine if the insults of severe DKA and its inflammatory cascade are associated with immune responses to SAgs. Development of Abs to the SAgs were determined by an ELISA using sera collected at three time points in relation to severe DKA (pH < 7.2). Results demonstrate significant differences between the development of Abs to VIM and a previously reported diastolic abnormality (DA) during DKA and its treatment and a NDA group at 2–3 months post DKA (p = 0.0452). A significant association is present between T1D duration (<3 years) and Abs to Kα1T (p = 0.0134). Further, Abs to MYO and VIM are associated with inflammatory cytokines. We propose that severe DKA initiates the synthesis of Abs to cardiac SAgs that are involved in the early immunopathogenesis of DC in young patients with T1D.

Keywords:

• Cardiac antibodies
• cardiac self-antigens
• diabetic ketoacidosis
• diastolic abnormality
• systemic inflammatory response

Acknowledgements

The authors gratefully acknowledge Drs. I. Fiordalisi, D. Hannon, and the PICU Diabetic Ketoacidosis team at East Carolina University Medical Center for their diligent patient care and assistance with this project. The authors are also appreciative for the helpful suggestions of J. Oliver of the Immunology Laboratory at the Medical College of Georgia (GRU).

Declaration of interest

The authors report no conflicts of interest. The authors alone are responsible for the content and writing of the paper. T. M. is supported by HL056643 and Barnes Jewish Christian Foundation.

Supplementary materials available online.