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Agonistic autoantibodies against B2-adrenergic receptors correlating with macrovascular disease in longstanding diabetes type 2

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Abstract

Aims

Agonistic autoantibodies directed against adrenergic, endothelin, and angiotensin receptors are known as pathogenic factors in disease-causing vascular impairments such as Buergers’ disease, dilatative cardiomyopathy, dementia, and preeclampsia. Diabetes mellitus also causes micro- and macrovascular damages, but pathogenesis is still not fully understood. Following indications for a pathogenic role of the mentioned antibodies from our preliminary investigations, we investigated the prevalence in a bigger cohort of patients with longstanding diabetes with or without diabetic complications.

Methods

We included 200 patients in four groups (grouping due to duration of diabetes and presence of complications) from our university polyclinic with longstanding diabetes mellitus type 2 and evaluated the prevalence of the agonistic autoantibodies using ELISA technique.

Results

Antibodies directed against the alpha1-(39%), the first extracellular loop of the beta2-(34,5%), and the first extracellular loop of the beta1-adrenergic receptor (29,0%) were the most often detectable. With progression of diabetes and its complications, we found a decrease in the prevalence of the antibodies. Regression analyses revealed a positive association of antibodies against the first loop of the beta2-receptor and the presence of macrovascular complications.

Conclusions

This investigation found mid frequent prevalence of agonistic autoantibodies in patients with longstanding diabetes mellitus type 2. The association between an antibody against one epitope and the presence of macrovascular complications may indicates a pathogenic linkage. This finding is inconsistent with our preliminary data and needs further evaluation, maybe by follow-up.

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Acknowledgements

The authors would like to thank all technical personal involved in sample acquisition and processing. We also appreciate Marion Bimmler from E.R.D.E-AAB-Diagnostics GmbH, Berlin, Germany. She performed the laboratory investigations and consulted the data analyses.

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Authors and Affiliations

  1. Department of Internal Medicine III, Jena University Hospital, Jena, Germany

    Christoph Werner, Nicolle Müller & Ulrich Alfons Müller

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  1. Christoph Werner
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  2. Nicolle Müller
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  3. Ulrich Alfons Müller
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Corresponding author

Correspondence to Nicolle Müller.

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Conflict of interest

Investigations were substantially financed by Fresenius medical care GmbH, Germany. The sponsor had no influence on study design, data processing or manuscript editing. C.W. received travel funding by Novartis oncology. All authors declare not further conflicting interests.

Ethical approval

All investigations were approved by ethics-committee of the University of Jena (number of decision: 4916-09/16).

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All patients gave informed consent to laboratory investigations and data processing.

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Werner, C., Müller, N. & Müller, U.A. Agonistic autoantibodies against B2-adrenergic receptors correlating with macrovascular disease in longstanding diabetes type 2. Acta Diabetol 56, 659–665 (2019). https://doi.org/10.1007/s00592-019-01296-8

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