Prevention of Autoimmune Disease: The Type 1 Diabetes Paradigm

Leonard C. Harrison, John M. Wentworth

Research output: Chapter in Book/Report/Conference proceedingChapter (Book)Otherpeer-review

Abstract

Prevention of autoimmune disease based on a mechanistic understanding of pathogenesis would be the ultimate triumph of immunological good over evil. Until a therapeutic intervention is shown to be completely safe, accurate prediction of clinical disease will be a prerequisite for prevention. For this reason alone, type 1 diabetes (T1D) is arguably the best paradigm for prevention. Although other autoimmune diseases are associated with the appearance of autoantibodies before clinical presentation, T1D exemplifies par excellence the application of autoantibody markers to preclinical diagnosis and prediction (in T1D relatives), and identification of high-risk individuals as candidates for prevention. The rising incidence of T1D and other autoimmune diseases is driven by environmental factors on a background of genetic susceptibility, implying that some degree of primary prevention, before the onset of disease, is feasible. Secondary prevention, after initiation of pathogenic autoimmunity but before clinical presentation, places a high premium on therapeutic modalities that are safe, which to date are applied only in T1D in the form of autoantigen-based vaccination to induce immune tolerance. Tertiary "prevention," after clinical presentation, equates with treatment of established disease. Certain agents are effective in slowing progression of some autoimmune diseases, e.g., biologics in rheumatoid arthritis, but multiple trials of immune and non-immune agents in T1D have failed to prevent loss of residual β cell function over the long term. Systematic study of the natural histories of autoimmune diseases from early life in relation to environmental exposures, together with the development of safer immunotherapeutic approaches and lessons learnt from ongoing clinical trials in T1D, should improve the prospects for autoimmune disease prevention.

Original languageEnglish
Title of host publicationThe Autoimmune Diseases
EditorsNoel R. Rose, Ian R. Mackay
Place of PublicationSan Diego CA USA
PublisherAcademic Press
Pages1191-1208
Number of pages18
Edition5th
ISBN (Print)9780123849298
DOIs
Publication statusPublished - 2014
Externally publishedYes

Keywords

  • Autoantibody
  • Autoimmune disease
  • Clinical trial
  • Immune
  • Mucosa
  • Preclinical
  • Prevention
  • Suppression
  • Tolerance
  • Type 1 diabetes

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