An explanation of how migraine headaches can trigger relapse in systemic lupus erythematosus.

Except for a few diseases of molecular mimicry such as rheumatic fever, post-streptococcal glomerulonephritis in children, and gluten-sensitive enteropathy, the cause of autoimmune diseases is unknown. Most autoimmune diseases are remitting-relapsing and the pathophysiology of either the initial attack or subsequent relapses is a mystery. Migraine headaches in systemic lupus erythematosus patients are statistically associated with disease activity, i.e. the patients with bad lupus are the ones who get migraine. T lymphocytes reactive against self are normally suppressed by immunoregulatory T cells (Tregs), but suppression can be broken by CD28 ligation of Tregs. This raises intracellular levels of H2O2, which is a second messenger in the CD28 signaling cascade. Migraine headaches are often accompanied by systemic platelet activation and a brief but intense platelet oxidative burst which raises extracellular H2O2 levels to the point where H2O2 diffusing passively across lymphocyte cell membranes can raise intracellular H2O2 sufficiently to turn off regulatory T cell function via the CD28 signaling cascade. Passive diffusion of H2O2 mimics the effect of H2O2 formation triggered by CD28 ligation. This eliminates the immunosuppressive hold of Tregs on self-reactive T cells and the development or worsening of autoimmune disease ensues spontaneously.