Immune biomarkers in immunotherapeutic trials for type 1 diabetes: cui prodest?

Decades of research efforts aimed at upgrading type 1 diabetes (T1DM) treatment did not harvest much success besides improving insulin therapy, which remains the standard of care since 1922. Immunological strategies targeting autoimmune mechanisms, rather than their metabolic consequences, are highly demanded. A dealt of preclinical studies in animal models offered some promises, which were however not maintained once translated into human. All these immune intervention trials evaluated metabolic and clinical endpoints, namely C-peptide secretion, HbA(1c) and insulin requirements. While critical, we argue that these endpoints are insufficient and should be complemented with immune surrogate endpoints, i.e. biomarkers reflecting the immune modifications induced by such treatments. This is even more critical when clinical expectations are not met, in order to sort out the reasons of such failure, i.e. whether immune changes are not accomplished or whether, despite being accomplished, they are insufficient to translate into clinical benefits. Furthermore, these ancillary analyses may give precious indications to design further trials, i.e. to enroll patients with the best odds to respond to therapy and to follow-up their response.