Disease Interception in Autoimmune Diseases: From a Conceptual Framework to Practical Implementation

Abstract

The hallmark of autoimmunity, and perhaps many immune-mediated inflammatory diseases, is the inappropriate recognition of self-tissue resulting in subsequent effector reactions that ultimately damage the host. Numerous components may underlie these outcomes and likely include lack of central immune tolerance to self, breakdown of peripheral tolerance mechanisms that control inflammation, relevant stress signals that enhance and/or modify antigenicity of self-tissues, and a complex interplay between the host and the environment; including the emergent immuno-regulatory role of the microbiome. Much of the historical therapeutic success has focused on approaches that broadly dampen or modulate inflammatory mediators (e.g. success of anti-cytokine antibodies directed against tumor necrosis factor (TNF), or interleukins such as IL-6, IL-17, IL-1 in rheumatoid arthritis (RA), inflammatory bowel disease (IBD), psoriasis or small molecule kinase inhibitors) with little to no understanding of the earliest molecular triggers that underpin disease initiation [1, 2]. While anti-inflammatory approaches have yielded symptomatic benefits for the patients, a significant unmet medical need still exists particularly from the viewpoint of sustained disease remission and cessation of tissue-destructive biological processes. To this end, the ultimate therapeutic goal for autoimmune diseases would be to restore immune homeostasis as evidenced by inhibition of self-reactivity leading to reestablishment of a self-tolerant state.