Identification of Candidate Predictors of Lupus Flare

Systemic lupus erythematosus, the prototype systemic autoimmune disease, is characterized by extensive self-reactivity, inflammation, and organ system damage. Sustained production of type I interferon is seen in many patients and contributes to immune dysregulation. Disease activity fluctuates with periods of relative quiescence or effective management by immunosuppressive drugs, followed by disease flares. Tissue damage accumulates over time, with kidneys and cardiovascular system particularly affected. Identification of the underlying molecular mechanisms that precede clinical exacerbations, allowing prediction of future flare, could lead to therapeutic interventions that prevent severe disease. We generated gene expression data from a longitudinal cohort of lupus patients, some showing at least one period of severe flare and others with relatively stable disease over the period of study. Candidate predictors of future clinical flare were identified based on analysis of differentially expressed gene transcripts between the flare and non-flare groups at a time when all patients had relatively quiescent clinical disease activity. Our results suggest the hypothesis that altered regulation of genome stability and nucleic acid fidelity may be important molecular precursors of future clinical flare, generating endogenous nucleic acid triggers that engage intracellular mechanisms that mimic a chronic host response to viral infection.