Mechanisms and pathophysiology of autoimmune disease.

The first textbook on autoimmunity was published by Ian Mackay and McFarland Burnett in 1963. It was the first attempt to summarize existing knowledge on human autoimmunity. Since that time, there have been tens of thousands of experimental papers and numerous textbooks that focus on the diagnosis and treatment of human autoimmunity. There have been at least as many, if not more, directed at similar issues in animal models. Enormous strides have been made not only in diagnosis, but also in the pathophysiology and especially in treatment. We have gone from the era of simple HLA typing to deep sequencing and, more recently, epigenetic analysis. We have gone from the era of white blood cell differentials to detailed lymphoid phenotyping. We have gone from the era of simple antinuclear antibodies to detailed and sophisticated immunodiagnosis with recombinant autoantigens and disease-specific epitopes. We have gone from the era of using only corticosteroids to selective biologic agents. Diseases that were previously considered idiopathic are now very much understood as autoimmune. We are in the era of autoinflammatory reactions and the concept of both innate versus adaptive immunity in mediating immunopathology. In this edition of Clinical Reviews in Allergy and Immunology, we focus on key and cutting-edge issues in the pathophysiology of autoimmunity. The issues are very much oriented and driven by hypothesis, i.e., a prediction of events expected to occur based on observations. It is not meant to be a complete summary of potential mechanisms of autoimmunity, but rather an attempt to accelerate discussion and better understanding. The primary goal is obviously to help our patients with autoimmune disease.