In a previous study of 31 ADAMTS13-deficient TTP patients, 9 had other autoimmune co-morbid conditions, including non-destructive polyarthritis, Raynaud��s phenomenon, autoimmune endocrinopathies, discoid lupus and systemic lupus erythematosus. TTP shares several characteristics with SLE, including PD325901 demographic population targeted and flares or episodes separated by periods of relative health. SLE can clinically appear as thrombotic microangiopathy and is a differential diagnosis for observation of thrombocytopenia and microangiopathic hemolytic anemia. A review of case reports found 87 patients having clinical evidence for both TTP and SLE. A close relationship was demonstrated between childhood-diagnosed idiopathic TTP and later partial or complete SLE diagnosis. More recently, we showed a great GDC-0879 increase in the prevalence of SLE among TTP survivors. In addition, anti-nuclear autoantibodies, typical of though not specific for SLE, were detected in patients with acute and quiescent TTP. Elevated type I IFN, promoted by immune complexes comprised of RNA-binding proteins, including Ro, La, Smith and/or Nuclear Ribonuclear Protein, bound to anti- RNA-binding protein-specific autoantibodies, has emerged as a major driver of immune dysregulation in SLE. Such RNA-containing immune complexes activate plasmacytoid dendritic cells to produce type I IFN by triggering RNA-binding Toll-like receptors following Fc receptor- mediated uptake. Stimulation of RNA-binding Toll-like receptors in plasmacytoid dendritic cells normally promotes immune responses to viral pathogens. In SLE patients, however, elevated serum type I IFN activity and/or increased type I IFN-responsive gene expression associates with autoantibodies specific for RNA-binding proteins, elevated disease activity, particular genetic polymorphisms and major multi-organ involvement. The discovery of ANAs in patients with ADAMTS13-deficient TTP, increased prevalence of SLE after survival of TTP and case reports of TTP episodes following interferontherapy prompted us to examine ADAMTS13-deficient TTP patients in remission for evidence of underlying ANA-driven, type I IFN-mediated inflammation and further test for possible association with relapse. We report here that a subset of TTP patients have a type I IFN peripheral blood gene signature that associates with autoantibodies to RNA-binding proteins. However, these linked features did not associate with history of TTP relapse. In contrast, a ribosomal gene signature and select immune transcripts commonly expressed in T and natural killer lymphocytes demonstrated significant association with history of relapse in ADAMTS13-deficent TTP patients in remission.