Vahid Akbari, Alexandra Morgan, Michie Yasuda, Ulrich Schlecht, Sylvie McNamara, Hossein Asgharian, Christopher Tam, Rena Adachi, Elisa Contreras, Zhipei Gracie Du, Sandra Siemann, Hahn Zhao, Jeya Balaji Balasubramanian, Diane Balallo, Devanshee Sanghvi, Tarini Shankar, Sanjucta Dutta, Stefan Riedel, Stefanie Mattson, Daniel Burukhin, Florian Rubelt, Sowmi Utiramerur, Dinesh Kumar, Hamid Mirebrahim, Ramy Arnaout
Background: T and B cells are central to adaptive immunity, where they identify and neutralize foreign antigens and cancer neo-antigens. Large-scale elucidation of T- and B-cell receptors (TCRs and BCRs) through immune-repertoire sequencing promises novel diagnostics, prognostic markers, and therapeutic strategies. However, progress is hampered by small cohort sizes, a lack of real-world patient diversity, and heterogeneous sample processing, impeding cross-study comparability. To overcome these limitations, here we introduce the Human Blood Immunome Encyclopedia (HuBIE), comprising immune-repertoire data from 2,614 samples collected from 1,941 participants. The cohort includes a range of bloodstream infections, several cancer types, and control participants, with many individuals providing longitudinal samples. Methods: We employed Roche's immune receptor Primer Extension Target Enrichment (immunoPETE) platform to perform simultaneous targeted sequencing of T and B cells heavy chains including T-cell receptor β chains (TRB), T-cell receptor δ chains (TRD), and immunoglobulin heavy chains (IGH), thereby profiling TCRs and BCRs in all participants. We examined various aspects of the immune repertoire such as diversity, gene usage, chain fractions, and CDR3 features to provide a comprehensive description of immune-repertoire in cancer and bloodstream infections and examine variations across demographic variables such as age and race. Results: We find significant differences in TRB and IGH composition across ethnic groups, and show that the fall in repertoire diversity with age follows distinct patterns for TRB, TRD, and IGH and is accompanied by age-related differences in VJ gene usage. Finally, we demonstrate that greater immunological diversity is associated with improved survival for elderly participants. Conclusions: HuBIE constitutes a valuable resource for the immune-repertoire community, enabling large-scale mapping of the human immunome to accelerate development of diagnostics, prognostic biomarkers, and innovative therapeutic strategies.