A distinct T cell receptor signature associates with cardiac outcome in myocardial infarction patients

Myocardial infarction (MI) is associated with an inflammatory process mainly attributed to innate immune components. Very recently, the role of T-cells in both inflammation and healing has been suggested through various human and mouse studies. Previous studies showed that CD4+ and CD8+ T cells affect post-MI repair but did not investigate how to leverage T cell biology to predict post-MI outcomes in patients. For instance, the antigenic trigger of T-cells is still unknown in human. Indeed, others and we identified T-cell specific for myosin infiltrating the myocardium in mouse models of MI, recent studies identified expanded clones in human myocardium, altogether suggesting a tissue-specific T-cell activation. However, it is still unclear how acute post-MI immune responses shape long-term cardiac functional outcomes in individual patients. In this study, we analyzed the role of T-cell in predicting post-MI repair by analyzing the T-cell receptor (TCR) repertoire. Indeed, the TCR repertoire is now considered as a marker of the clinical status of individuals. Previous studies in infectious but also autoimmune contexts showed the potential of the TCR repertoire to predict the disease. Therefore, assessing the dynamic changes in global TCR repertoires may provide valuable information about the antigen-specific immune responses underlying post-MI healing. In our study, we carefully selected patients that suffered from MI on a prospective cohort. The TCR repertoire has been analyzed by next generation sequencing at the index hospitalization with the aim to identify features predict of their healing outcome assessed at 12 months post-MI. While no major variations have been found in diversity of TCR gene usage, we identified unique TCR signatures predicting one-year cardiac functional outcomes. Our result enables early immune-based risk stratification of MI patients and calls for larger studies to develop novel predictive biomarkers and possibly new therapeutics. ### Competing Interest Statement The authors have declared no competing interest. ### Funding Statement This work was supported by the European Research Area Network-Cardiovascular Diseases [ERANET-CVD JCT2018, AIR-MI Consortium to GCR (01KL1902), PPR (4168-B) and EMF (ANR-18-ECVD-0001)]. The ETiCS study was supported by the Bundesministerium fur Bildung und Forschung (BMBF), grant Molecular Diagnostics FKZ 01ES0901 and FKZ 01ES0802 (to V.B.J. and R.J.). KLG doctoral fellowship was supported by ERANET-CVD JCT2018 (ANR-18-ECVD-0001) and additional support from Sorbonne Universite. EMF work was supported by the iReceptorPlus (H2020 Research and Innovation Programme 825821) and SirocCo (ANR-21-CO12-0005-01) grants and the Institut Universitaire de France. GCR is supported by the Interdisciplinary Centre for Clinical Research Wurzburg [E-354]. GCR, UH, and SF received funding from the German Research foundation (through the Collaborative Research Centre Cardio-Immune interfaces SFB1525, grant number 453989101). ### Author Declarations I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained. Yes The details of the IRB/oversight body that provided approval or exemption for the research described are given below: The ethics committee of the university hospital of Wurzburg has approved this study (approval number 186/07) and all patients gave written informed consent. I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals. Yes I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance). Yes I have followed all appropriate research reporting guidelines, such as any relevant EQUATOR Network research reporting checklist(s) and other pertinent material, if applicable. Yes All data produced in the present study are available upon reasonable request to the authors.