Therapeutic tolerance in autoimmune disease.

Experimental immune tolerance induction, enabling tissues to be transplanted across animal strains, was first demonstrated in the 1950s. Therapeutic tolerance induction, whereby immune tolerance is used to treat or prevent transplant rejection, and as a treatment for autoimmunity, followed in the 1980s. Clinical translation has been slow but the pace of change is accelerating. Numerous strategies are now being tested clinically, ranging from monoclonal antibodies against T-cells, to peptide therapies, cellular therapies and microbiome manipulation. Furthermore, technology has advanced to the stage where we can start to monitor serological and cellular autoreactivity as biomarkers of response. In terms of autoimmunity, recognition of the prolonged phase of preclinical autoimmunity in several conditions, is leading to debate around treatment of at risk individuals, and trials in patients with prodromal clinical symptoms, such as seropositive arthralgia. Additionally, potent immunomodulatory drugs are achieving a substantial track record of safety. Putting these various factors together suggests that we can soon expect to see more trials of tolerogenic strategies in pre-clinical disease, with intensive immune monitoring to guide therapy.