Molecular basis and novel therapy of systemic lupus-associated thrombosis

SLE is a complex autoimmune disease with great clinical heterogeneity. Despite significant progress in genetic surveys, the cumulative evidence supports observations first made in twin studies, much of the risk for disease derives from environmental factors. Of all potential factors, the influence of our microbiome (i.e., the consortium of microorganisms that reside within our bodies) has recently been implicated in other inflammatory and autoimmune clinical diseases, Moreover, certain species in the gut microbiome can influence responses from both innate and adaptive immunity. While certain bacterial species can modulate T cell responses, others produce factors that induce interferon production, which we speculate may be linked to lupus pathogenesis. Unbiased surveys for the representation of bacterial species can now be readily performed using high throughput DNA sequencing of ICS rRNA genes. We speculate that the specific microbiome of a SLE patient directly influences the initiation and perpetuation of clinical active lupus, which may involve the induction of the disease-associated interferon signature in peripheral blood cells. Our project will perform the first surveys of the gut associated microbiota of SLE patients, and assess for the possible relationships between SLE disease activity, clinical manifestations and effects on the host immune system.