Progress in immune-based therapies for type 1 diabetes

Abstract

Immune-based therapies that prevent type 1 diabetes or preserve metabolic function remaining at diagnosis have become a major objective for funding agencies and international trial consortia, and receive backing from notable patient advocate groups. The development of immune-based therapeutic strategies in this arena requires a careful balancing of the risks of the therapy against the potential benefits, because many individuals are diagnosed or identified as being at increased risk of disease in early childhood, a period when manipulation of the developing immune system should be undertaken with caution. In addition, a therapy exists (daily insulin injection) that is life-saving in the acute stages of disease and can be used effectively over a lifetime as maintenance. Conversely, the disease is increasing in incidence; is peaking in ever-younger age groups; carries significant risk of increased morbidity and early mortality; and remains difficult to manage effectively in many settings. With these issues in mind, in this article we review progress towards immune-based strategies for this chronic autoimmune disease.

Fig. 1

Bar charts show the number of clinical trials in different categories according to the natural history of type 1 diabetes (prevention, intervention) and treatment modality (none- or antigen-specific).

Fig. 2

Venn diagram shows the number of types of therapies used in different modalities (mono- and combination; antigen and non-antigen-specific) and the overlap between them.

Fig. 3

Frozen pancreas tissue section from an organ donor who was diagnosed with type 1 (T1D) diabetes 1 year earlier. The section was stained for insulin (green, top) and human leucocyte antigen (HLA)-ABC (red, bottom). Individual images were captured by confocal microscopy and automatically combined in-silico into a section-wide overview figure. Note the distinct region in the upper right corner where some insulin-producing beta cells are still present. These remaining insulin-positive islets also hyperexpress major histocompatibility complex (MHC) class I, as evident in the lower panel. Thus, this is a prime example of the lobular distribution of both beta cell loss and immune pathology in T1D. Samples courtesy of Network for Pancreatic Organ Donors with Diabetes (nPOD) (case 6052) and kindly provided by Dr Ken Coppieters.