Next 5 years in autoimmunity: predictive diagnostics, immune signatures, and personalized immune therapy.

Autoimmune diseases are experiencing a conceptual transformation in the traditional system of phenotypical classification to a more molecularly stratified system. The next five years suggest that immunological and metabolic signals, such as autoantibody patterns, epitope-spreading patterns, and inflammatory signals of microbiome interactions, will frequently predict clinical illness making the preclinical period a critical predictive and intervention time. Simultaneously, single-cell and multi-omic profiling are being used to discover molecular endotypes and pathogenic immune programs which can more effectively explain the heterogeneity of autoimmune diseases. Such insights are also incorporated more and more with computational methods, such as digital immune modeling, to allow for individual risk assessment and disease prediction. The combination of these advancements is hastening the shift toward precision immunology, where predictive diagnostics and targeted immune-modulating therapies can be implemented sooner and more successfully. This review synthesizes the major mechanistic innovations over the past few years and describes how predictive biomarkers, molecular endotyping, and novel treatment regimens in the coming years are likely to transform the diagnosis and treatment of autoimmune diseases.