Detection of heart-reactive autoantibodies in patients hospitalized for acute heart failure – First results from the prospective AHF-Immunomonitoring Cohort Study

B. Afshar (Würzburg)¹, D. D. Pelin (Würzburg)², M. Heil (Würzburg)³, T. Kerkau (Würzburg)³, E. Kaiser (Würzburg)⁴, J. Lamers (Würzburg)⁴, J. Pätkau (Würzburg)⁴, M. Bauser (Würzburg)⁵, F. Kerwagen (Würzburg)⁵, G. Ramos (Würzburg)⁵, U. Hofmann (Würzburg)⁶, S. Frantz MD (Würzburg)⁴, S. Störk MD PhD1 (Würzburg)⁴, N. Beyersdorf (Würzburg)⁷, C. Morbach (Würzburg)^6
1Institut für Virologie und Immunbiologie Würzburg, Deutschland; ²Universitätsklinikum Würzburg Deutsches Zentrum für Herzinsuffizienz/DZHI Würzburg, Deutschland; ³Institute for Virology and Immunobiology immunology Würzburg, Deutschland; ⁴Comprehensive Heart Failure Center, Department for Clinical Research and Epidemiology, University and University Hospital Würzburg Würzburg, Deutschland; ⁵Universitätsklinikum Würzburg Deutsches Zentrum für Herzinsuffizienz Würzburg, Deutschland; ⁶Universitätsklinikum Würzburg Medizinische Klinik und Poliklinik I Würzburg, Deutschland; ⁷Universität Würzburg Institut für Virologie und Immunbiologie Würzburg, Deutschland

Recently, we have shown in a retrospective study that induction of heart-reactive autoantibodies (HRA) in the wake of acute decompensation of heart failure was associated with a worse clinical prognosis. To confirm these data and to obtain a better understanding of the immunological processes triggered by decompensation of heart failure, we initiated the prospective 'Acute Heart Failure-Immunomonitoring Cohort Study' (AHF-ImmunoCS), which follows patients with AHF for 18 months after index hospitalization including serial collection of biomaterials. Of the first 45 patients enrolled, indirect immunofluorescence (IFT) of samples obtained at baseline and 6 months later confirmed de novo induction of HRA in 25% of patients (published data: 32%). Furthermore, in 16% of patients we detected HRA already six weeks after acute decompensation. In a separate approach aiming to quantify HRA, we established flow cytometric assays using Dynabeads ^TM coated with Myosin Heavy Chain 6 or 7, Myosin Light Chain 7, Troponin I3 or Tropomyosin 1 as immobilized antigens. We chose these antigens as they are strongly, in case of Myosin Light Chain 7 even exclusively, expressed by cardiomyocytes according to The Human Protein Atlas and as they have previously been reported to be targets of HRA. Comparing baseline samples of 'high-risk' patients, ie those with a negative IFT at baseline, to samples of healthy controls revealed that, with the exception of Myosin Heavy Chain 7, fewer patients expressed HRA than healthy controls. Comparing baseline samples to samples obtained 6 weeks and 6 months after an acute decompensation showed, independent of IFT status at baseline, clear changes in reactivities to these autoantigens with great interindividual differences between patients. Future correlation of HRA and defined autoantibody quality and quantity with clinical outcome will pinpoint to novel biomarkers for the clinical course of acute heart failure and, ideally, lead to the development of immunomodulatory interventions. This study was supported by a grant from the DFG (SFB1525 - project C05).