Constructing immunoprofiles to deconstruct disease complexity in pemphigus.

The complex etiology of multifactorial diseases such as pemphigus vulgaris complicates mechanistic investigations and confounds current therapeutic approaches. Two major sources contribute to the overall complexity of disease. Biological complexity involves the disruption of multiple immune pathways that underlie autoimmune destruction in the skin. Overlaying this altered immunobiology is clinical complexity that is manifest as heterogeneous presentations of disease. Merging cumulative data on immune dysfunction with the detailed clinical information can be expected to allow the deconstruction of the processes that lead to specific disease presentations. Our group has undertaken comprehensive analyses in stratified patient populations to assign T cell, cytokine, and autoantibody immunoprofiles linked to defined constant and variable clinical parameters. We propose the concept of a "disease array" that is based on a matrix of supporting biological and clinical information that can be used to guide the development of next-generational tools that enhance our ability to diagnose, prognose, and individually treat disease.