Biomedical Science Session: Short Contributed Talks
AIRR Community Meeting VII - Learnings and Perspectives
June 3-6, 2024
University of Porto, Porto, Portugal
www.antibodysociety.org/the-a...
00:08 "Understanding the role of T-cell receptor repertoire in T1D status"
Puneet Rawat, University of Oslo, Postdoctoral Fellow
Although Islet autoantibodies (AAb) are clinically used in the diagnosis of disease, AAb only serve as a marker of autoantigen presentation and not involved in disease pathogenesis. However, T cells are hypothesized to be directly pathogenic and responsible for the destruction of β-cells, highlighting the importance of developing a T-cell biomarker for T1D.
We have sequenced 2250 TCRβ repertoires containing 1105, 625, 59 and 366 repertoires for T1D, first degree relatives, second degree relatives and healthy controls, respectively. The standard repertoire analysis (e.g. diversity profile, Morisita-Horn similarity index etc.) were not able to classify the T1D repertoires from the healthy ones. Therefore, we implemented a Deep learning model entitled “DeepRC” to classify the T1D and healthy repertoires and identify the biomarker associated with T1D. The DeepRC method showed classification accuracy of ~80% on the test dataset. We also tested conventional ML approaches, which had lower prediction performance compared to DeepRC. We also looked into the association between HLA alleles and CDR3β phenotypes and observed that CDR3 risk score was able to classify different T1D status.
10:31 "The regulatory T-cell receptor repertoire as an early predictor of SLE disease progression and response to immunotherapy"
Martin Pezous, Sorbonne-Université, PhD student
While autoantibodies are associated with autoimmune disease (AD) diagnosis, the role of T-cells has often been overlooked. It is now evidenced that T-cells, and notably regulatory T-cell (Tregs) deficiencies, are linked to AD pathophysiology. In particular, a Treg-targeting immunotherapy, such as low-dose IL-2 (ld-IL2) has been shown to improve clinical state, notably in systemic lupus erythematosus (SLE). By studying the T-cell receptor (TCR) repertoire, we can now provide insights onto AD pathogenesis and treatment efficacy. This study leverages machine learning to analyze TCR repertoires in SLE patients, focusing on the biological efficacy of ld-IL2.
23:27 "Decoding the T-Cell Receptor Repertoire in Chronic Autoimmune Arthritis"
Vincent Van Deuren, University of Antwerp
We curated a database of synovial fluid TCR repertoires comprising more than 14 different studies and three million unique clonotypes. Empowered by a statistical framework, our meta-analysis reveals novel distinct TCR repertoire patterns among different arthritis groups, age categories, and T-cell subsets. In addition, we highlight the presence of oligoclonal T-cell populations reactive to common viral epitopes in the synovial fluid, including those from human cytomegalovirus and SARS-CoV-2. Importantly, specific TCR clusters thought to drive arthritis were identified, and their phenotype characterized in our single-cell data, ultimately providing new insights into the immunological landscape of chronic arthritis.