Bieber K, Hundt JE, Yu X, Ehlers M, Petersen F, Karsten CM, Köhl J, Kridin K, Kalies K, Kasprick A, Goletz S, Humrich JY, Manz RA, Künstner A, Hammers CM, Akbarzadeh R, Busch H, Sadik CD, Lange T, Grasshoff H, Hackel AM, Erdmann J, König I, Raasch W, Becker M, Kerstein-Stähle A, Lamprecht P, Riemekasten G, Schmidt E, and Ludwig RJ
Approximately 5% of the world-wide population is affected by autoimmune diseases. Overall, autoimmune diseases are still difficult to treat, impose a high burden on patients, and have a significant economic impact. Like other complex diseases, e.g., cancer, autoimmune diseases develop over several years. Decisive steps in the development of autoimmune diseases are (i) the development of autoantigen-specific lymphocytes and (often) autoantibodies and (ii) potentially clinical disease manifestation at a later stage. However, not all healthy individuals with autoantibodies develop disease manifestations. Identifying autoantibody-positive healthy individuals and monitoring and inhibiting their switch to inflammatory autoimmune disease conditions are currently in their infancy. The switch from harmless to inflammatory autoantigen-specific T and B-cell and autoantibody responses seems to be the hallmark for the decisive factor in inflammatory autoimmune disease conditions. Accordingly, biomarkers allowing us to predict this progression would have a significant impact. Several factors, such as genetics and the environment, especially diet, smoking, exposure to pollutants, infections, stress, and shift work, might influence the progression from harmless to inflammatory autoimmune conditions. To inspire research directed at defining and ultimately targeting autoimmune predisease, here, we review published evidence underlying the progression from health to autoimmune predisease and ultimately to clinically manifest inflammatory autoimmune disease, addressing the following 3 questions: (i) what is the current status, (ii) what is missing, (iii) and what are the future perspectives for defining and modulating autoimmune predisease., Competing Interests: Declaration of Competing Interest Christian M. Karsten has received honoraria for speaking from Alexion, and Vifor Pharma during the last 3 years. Peter Lamprecht has received honoraria for speaking or consulting or has obtained research grants from BMBF, BMS, DFG, DGRh, GSK, Janssen, Roche, UCB, and Vifor Pharma during the last 3 years. Gabriela Riemekasten has received honoraria for speaking or consulting or has obtained research grants from Abbvie, Astra Zeneca, Boehringer Ingelheim, Bristol Myers Squibb, Chugai, Galapagos, Janssen Cilag, Novartis, Pfizer during the last 3 years. Enno Schmidt receives grant funding from Euroimmun, Incyte, Dompe, Admirx, Synthon/biondis, Bayer, Pharmix, Alpine Immune, AstraZeneca, Sanofi, ArgenX, UCB, Novartis, Biotest, Fresenius Medical Care, and is consulting for Roche, Imevax, Thermo Fisher, Janssen, Topas, Bristol-Myers Squibb, Almirall, and Chugai. Ralf J. Ludwig has received honoraria for speaking or consulting or has obtained research grants from Novartis, Lilly, Bayer, Dompe, Synthon, Argen-X, and Incyte during the last 3 years. All other authors declare no conflict of interest., (Copyright © 2022 Elsevier B.V. All rights reserved.)