Heterogeneity of autoimmune diseases: pathophysiologic insights from genetics and implications for new therapies

Nat Med. 2015 Jul;21(7):730-8. doi: 10.1038/nm.3897. Epub 2015 Jun 29.


Recent advances in genome-wide association studies (GWAS) across autoimmune and immune-mediated diseases have augmented our understanding of pathogenic mechanisms underlying these diseases. This has further highlighted their heterogeneous nature, both within and between diseases. Furthermore, varying responses to therapy have also served to underline the importance of this heterogeneity in the manner in which these diseases are diagnosed and treated. Here we discuss our current understanding of the shared pathways of autoimmunity, including the tumor necrosis factor (TNF), major histocompatibility complex (MHC), interleukin 23 receptor (IL23R) and protein tyrosine phosphatase non-receptor type 22 (PTPN22) pathways. In addition, we summarize effective specific therapies tested across major autoimmune diseases, highlighting the insight they have provided into disease mechanisms and their implications for potential future improvements.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Autoimmune Diseases / genetics*
  • Autoimmune Diseases / immunology
  • Autoimmune Diseases / physiopathology*
  • Autoimmune Diseases / therapy
  • Genetic Heterogeneity*
  • Humans
  • Lymphocyte Activation / immunology
  • Molecular Targeted Therapy*
  • Phenotype
  • Signal Transduction