Mapping genes and pathways in autoimmune disease

Identifying novel genes and pathways controlling T-cell activation holds the promise of developing novel therapies for autoimmune disease and cancer. Recent advances in the human genome project have shown that it is timely for small groups searching for this Holy Grail to rethink their options. In this review, some alternative strategies employed in pursuing novel disease pathways in rodents and humans, including recent results, are presented. Examples include the murine Roquin and Ncf1 genes, and the PTPN22 gene identified in humans. The potential benefit of reducing the heterogeneity of clinically defined diseases by the careful phenotyping of patients, cells and lesions using advanced molecular biology and imaging techniques is highlighted.