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The Lost Immunological Innocence of Biological Scaffolds for TAVI

24 Pages Posted: 8 Oct 2020

See all articles by Cecilia Veraar

Cecilia Veraar

Medical University of Vienna - Department of Anaesthesiology, General Intensive Care and Pain Medicine

Matthias Koschutnik

Medical University of Vienna - Department of Internal Medicine II

Christian Nitsche

Medical University of Vienna - Department of Internal Medicine II

Maria Laggner

Medical University of Vienna - Division of Thoracic Surgery

Dominika Polak

Medical University of Vienna - Department of Pathophysiology and Allergy Research

Barbara Bohle

Medical University of Vienna - Department of Pathophysiology and Allergy Research

Michael Mildner

Medical University of Vienna - Department of Dermatology

Andreas Mangold

Medical University of Vienna - Department of Internal Medicine II

Bernhard Moser

Medical University of Vienna - Division of Thoracic Surgery

Julia Mascherbauer

Medical University of Vienna - Department of Internal Medicine II

Hendrik J. Ankersmit

Medical University of Vienna - Laboratory for Cardiac and Thoracic Diagnosis, Regeneration and Applied Immunology

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Multiple version iconThere are 3 versions of this paper

Abstract

Background: Transcatheter aortic valve implantation (TAVI) is rapidly replacing cardiac surgery due to its minimal invasiveness and practicability. Midterm immunological studies on the biocompatibility of galactose-alpha-1,3-galactose (α - Gal)-carrying bioprosthetic heart valves (BHVs) for TAVI are not available. In this study we investigated whether BHVs employed for TAVI augment an α - Gal-specific antibody-dependent and antibody-independent immune response 3 months post TAVI.

Methods: This prospective observational study included 27 patients with severe aortic valve stenosis undergoing TAVI and 10 patients with severe mitral valve regurgitation treated with a transcatheter MitraClip procedure. Serum samples were collected before and 90 days after treatment and analyzed for concentrations of α - Gal-specific IgG, IgG subclasses and IgE, complement C3a, NETosis specific CitH3, and the systemic inflammation markers sST2 and IL-33 via ELISA.

Findings: Three months after TAVI we found significantly increased serum concentrations of α - Gal-specific IgG3, C3a, citH3 levels, and sST2 (p=0·002, p=0·001, p=0·025, and p=0·039, respectively). Sensitization of α - Gal-specific IgE antibodies occurred in 55% of all patients after TAVI.

Interpretation: Our results indicate that TAVI elicits a specific humoral immune response against α - Gal and causes an unspecific humoral inflammation compared with patients undergoing MitraClip implantation. This observation will lead to a better understanding of post intervention morbidity and the long-term durability of bioprostheses and indicates that caution is appropriate when designing implantation strategies for younger patients.

Funding Statement: This work was supported by the institutional surgical research facility ARGE Ankersmit (FOLAB Chirurgie)

Declaration of Interests: None of the authors have any conflict of interest to declare.

Ethics Approval Statement: Ethics approval was obtained from the Institutional Ethics Committee of the Medical University of Vienna (EK 2218/2016). All experiments were performed in accordance with the approved ethical guidelines. Written informed consent was obtained from all study participants.

Keywords: TAVI, biological scaffolds, aortic valve disease, MitraClip, Alpha-Gal, complement, NETosis, sST2/IL-33

Suggested Citation

Veraar, Cecilia and Koschutnik, Matthias and Nitsche, Christian and Laggner, Maria and Polak, Dominika and Bohle, Barbara and Mildner, Michael and Mangold, Andreas and Moser, Bernhard and Mascherbauer, Julia and Ankersmit, Hendrik J., The Lost Immunological Innocence of Biological Scaffolds for TAVI. Available at SSRN: https://ssrn.com/abstract=3675462 or http://dx.doi.org/10.2139/ssrn.3675462

Cecilia Veraar (Contact Author)

Medical University of Vienna - Department of Anaesthesiology, General Intensive Care and Pain Medicine ( email )

Vienna
Austria

Matthias Koschutnik

Medical University of Vienna - Department of Internal Medicine II

Vienna
Austria

Christian Nitsche

Medical University of Vienna - Department of Internal Medicine II

Vienna
Austria

Maria Laggner

Medical University of Vienna - Division of Thoracic Surgery

Austria

Dominika Polak

Medical University of Vienna - Department of Pathophysiology and Allergy Research

Vienna
Austria

Barbara Bohle

Medical University of Vienna - Department of Pathophysiology and Allergy Research

Vienna
Austria

Michael Mildner

Medical University of Vienna - Department of Dermatology

Vienna
Austria

Andreas Mangold

Medical University of Vienna - Department of Internal Medicine II

Vienna
Austria

Bernhard Moser

Medical University of Vienna - Division of Thoracic Surgery

Austria

Julia Mascherbauer

Medical University of Vienna - Department of Internal Medicine II

Vienna
Austria

Hendrik J. Ankersmit

Medical University of Vienna - Laboratory for Cardiac and Thoracic Diagnosis, Regeneration and Applied Immunology ( email )