The cause of systemic lupus erythematosus: implication of ‘self-organized criticality theory of autoimmunity’ on the pathogenesis of systemic lupus erythematosus

Abstract

To determine the cause of autoimmune disease, instead of chasing a causative autoantigen or seeking the cause of autoreactivity, we have studied the integrity of the immune system by stimulating the system maximally with an antigen (i.e., providing an external disturbance, just like testing the capability of an automobile in an extreme condition like an F1 race). Our research suggests that systemic autoimmunity (i.e., systemic lupus erythematosus) is the inevitable consequence of overstimulating the host’s immune system with an antigen to levels that surpass the system’s stability limit (i.e., self-organized criticality), a theory we call the ‘self-organized criticality theory’ of autoimmunity. We show that autoantibodies are not induced by cross-reaction to the antigen, but by de novo T-cell receptor revision giving rise to a novel T cell type we term an autoantibody-inducing CD4 T cell (aiCD4 T cell). This aiCD4 T cell helps B cells to induce a variety of autoantibodies and facilitates the generation of...