Immune Mechanisms and Pathways Targeted in Type 1 Diabetes.
PURPOSE OF REVIEW
The immunosuppressive agent cyclosporine was first reported to lower daily insulin dose and improve glycemic control in patients with new-onset type 1 diabetes (T1D) in 1984. While renal toxicity limited cyclosporine's extended use, this observation ignited collaborative efforts to identify immunotherapeutic agents capable of safely preserving β cells in patients with or at risk for T1D.


RECENT FINDINGS
Advances in T1D prediction and early diagnosis, together with expanded knowledge of the disease mechanisms, have facilitated trials targeting specific immune cell subsets, autoantigens, and pathways. In addition, clinical responder and non-responder subsets have been defined through the use of metabolic and immunological readouts. Herein, we review emerging T1D biomarkers within the context of recent and ongoing T1D immunotherapy trials. We also discuss responder/non-responder analyses in an effort to identify therapeutic mechanisms, define actionable pathways, and guide subject selection, drug dosing, and tailored combination drug therapy for future T1D trials.
['Jacobsen|Laura M|LM|', 'Newby|Brittney N|BN|', 'Perry|Daniel J|DJ|', 'Posgai|Amanda L|AL|', 'Haller|Michael J|MJ|', 'Brusko|Todd M|TM|']
D015551:Autoimmunity D015415:Biomarkers D003922:Diabetes Mellitus, Type 1 D006801:Humans D007167:Immunotherapy D011322:Primary Prevention D013601:T-Lymphocytes
Type 1 diabetes Autoimmunity Clinical trial Immune therapy Prevention Treatment