The traditional overarching concept of disease pathogenesis entails the natural history of
disease, i.e. the concept that any disease is a unified entity from beginning to termination. The concept
of the natural history of disease encourages researchers and clinicians alike to conceptualize all clinical
signs and symptoms in a patient as manifestations of a single disease process. Our experiences in
dissecting the genetic control of autoimmune diseases and autoimmune phenotypes suggest that for
many autoimmune processes, an alternative conceptual framework may be more useful. We term this
approach a "modular" theory of autoimmunity. "Modules" are distinct, genetically controlled clinical
or pathological phenotypes which can interact to construct a disease process. Modules may interact
additively, synergistically, or antagonistically in any given individual. Multiple modules can coexist and
produce unique disease phenotypes. We illustrate this concept with examples from the murine autoimmune
model of type one diabetes, the nonobese diabetic (NOD) mouse. |