The Future of Blood Testing Is the Immunome

Abstract

It is increasingly clear that an extraordinarily diverse range of clinically important conditions—including infections, vaccinations, autoimmune diseases, transplants, transfusion reactions, aging, and cancers—leave telltale signatures in the millions of V(D)J-rearranged antibody and T cell receptor [TR per the Human Genome Organization (HUGO) nomenclature but more commonly known as TCR] genes collectively expressed by a person’s B cells (antibodies) and T cells. We refer to these as the immunome. Because of its diversity and complexity, the immunome provides singular opportunities for advancing personalized medicine by serving as the substrate for a highly multiplexed, near-universal blood test. Here we discuss some of these opportunities, the current state of immunome-based diagnostics, and highlight some of the challenges involved. We conclude with a call to clinicians, researchers, and others to join efforts with the Adaptive Immune Receptor Repertoire Community (AIRR-C) to realize the diagnostic potential of the immunome.

Molecular Big Data in Sports Sciences: State-of-Art and Future Prospects of OMICS-Based Sports Sciences

“…The term “immunome” has been coined to indicate the incredibly diverse and vast individual’s repertoire of antibodies, B cell receptors and T cell receptors (TRs), that can be generally assessed from the blood, and consists of approximately 50,000–440,000 B lymphocytes and 600,000–3,500,000 T lymphocytes per ml in apparently healthy adults ( Arnaout et al, 2021 ). Exercise can be conceived as a “molecular choreography,” that is to say, as a concerted series of biological, and cellular processes at the level of the cardiovascular, endocrine, and immunologic systems ( Contrepois et al, 2020 ).…”

Highly multiplexed immune repertoire sequencing links multiple lymphocyte classes with severity of response to COVID-19

“…While the adaptive immune system is well armed to eliminate pathogens, it can also contribute to tissue injury and severe disease progression. 8 , 9 Recent reports have documented a strong association between human leukocyte antigen (HLA) genotypes and COVID-19 disease severity, further underscoring the role of both hereditary and somatic components of the adaptive immune system in this disease. 10 , 11 While specific SARS-CoV-2 antigen T cell receptors and monoclonal antibodies have been identified, there is still a lack of understanding of measures and dynamics of the coordinated adaptive immune response in individuals with COVID-19 at the immune receptor repertoires level.…”

Biological controls for standardization and interpretation of adaptive immune receptor repertoire profiling

“…AIRR sequencing (AIRR-seq) provides insights into the immune status of an individual at steady-state or in altered conditions such as malignancy, autoimmune disease, immunodeficiency, infectious disease, or vaccination, and allows comparison of B- and T-cell populations between individuals and time points ( Benichou et al, 2012 ; Kirsch et al, 2015 ; Dziubianau et al, 2013 ; Hou et al, 2016 ; Ghraichy et al, 2018 ). AIRR-seq permits the description and quantification of global diversity and characteristics of AIRR, the identification of clonal expansions, the tracking of particular clonotypes, and the prediction of their specificities ( Miho et al, 2018 ; Zvyagin et al, 2020 ; Sidhom et al, 2018 ; Glanville et al, 2017 ; Huang et al, 2020 ; Jokinen et al, 2021 ; Akbar et al, 2021 ; Hayashi et al, 2021 ) as well as the antibody selection through phage display ( Rouet et al, 2018 ; Ravn et al, 2013 ), thereby providing opportunities for new biomarker identification ( Gittelman, 2021 ; Dines, 2020 ), therapeutic antibody discovery ( Akbar et al, 2021 ; Richardson et al, 2021 ), CAR-T cell bioengineering ( Sheih et al, 2020 ), vaccine development, cancer diagnostics and treatment ( Linette et al, 2019 ; Zhang et al, 2018 ; Lu et al, 2018 ), including neoantigen discovery ( Chiou et al, 2021 ; Richters et al, 2019 ) and immune intervention monitoring in diverse pathologies, such as stem cell transplantation ( Robinson, 2015 ; Fink, 2019 ; Jiang et al, 2019 ; Jacobsen et al, 2017 ; Theil, 2017 ; Link-Rachner et al, 2019 ; Rubelt et al, 2017 ; Parola et al, 2018 ; Georgiou et al, 2014 ; Arnaout et al, 2021 ; Anand et al, 2021 ).…”