Genetic underpinnings of autoimmunity--lessons from studies in arthritis, diabetes, lupus and multiple sclerosis.

Autoimmunity has been studied for more than four decades, but its genetic origins have remained a mystery. The recent past has witnessed an exponential growth in our understanding of autoimmunity resulting from both forward and reverse genetic approaches. More than 40 genes have been shown to precipitate systemic autoimmunity when genetically manipulated. In addition, reverse genetic studies in various autoimmune diseases have successfully guided researchers to specific locations on the genome that are associated with disease susceptibility. Buried within these genomic intervals lies a further treasure chest of autoimmunity genes. Efforts to unmask these culprit genes have yielded the very first clues about how an elaborate cast of players may be at work to orchestrate autoimmunity.