https://doi.org/10.1007/s00392-025-02625-4
1Institute for Virology and Immunobiology Würzburg, Deutschland; 2Universitätsklinikum Würzburg Deutsches Zentrum für Herzinsuffizienz/DZHI Würzburg, Deutschland; 3Universitätsklinikum Würzburg Medizinische Klinik und Poliklinik I Würzburg, Deutschland; 4Universitätsklinikum Würzburg Medizinische Klinik I, Kardiologie Würzburg, Deutschland
Abstract
In a retrospective study we have recently shown that induction of heart-reactive autoantibodies (HRA) in the wake of acute decompensation of heart failure predicts worse outcomes. 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 aims to follow 381 patients after an index hospitalization with AHF for a period of 18 months and provides serial collection of biomaterials.
Of the first 145 patients enrolled and using samples obtained at baseline and at the 6-months follow-up, indirect immunofluorescence (IFT) confirmed de novo induction of HRA in 19% of patients (previously published data: 32%). By analyzing sera 6 six weeks after acute decompensation, we now observed that of these 19% almost 74% had already developed HRA by this timepoint. In a parallel approach focused on cellular immunophenotyping, we utilized high-resolution spectral flow cytometry with 30+ parameter panels to identify lymphocytic and myeloid subsets of peripheral blood leukocytes on 55 samples.
We compared samples from patients who expressed HRA de novo (and, hence, are considered at high risk) and patients who did not, and found that the de novo group had a higher CD4 + to CD8 + T cell ratio (Figure 1). In addition, among CD4 + T cells, we found higher frequencies of naïve conventional, ie non-regulatory, T cells, effector cells, resting regulatory T cells, and Th1 cells in de novo patients versus controls. We also observed higher proportions of both B and NK cells among total lymphocytes. Among CD33 + myeloid cells, classical monocytes and conventional dendritic cells were elevated in de novo versus non- de novo patients. So far, our analyzes suggest that at least for some subsets like classical monocytes the observed differences remained stable from baseline to at least the 6-month follow-up timepoint.
Association of the immunological parameters with disease progression and rehospitalization for worsening HF or death within an 18-month follow-up period will allow us to better understand how these immunophenotypes influence prognosis of AHF patients.
This study was supported by a grant from the DFG (SFB1525 - project C05).
Figure1: CD4/CD8 ratio in control and de novo cohorts. Stats: Mann Whitney test. ** p < 0.01.