Neutrophils in Lupus Pathogenesis

Baylor Research Institute, Dallas TX

Investigators

Linked publications & trials

Abstract

SLE is a particularly aggressive disease in children, and represents an unmet medical need. We have[unreadable] found that SLE is characterized by major alterations in the dendritic cell system where uncontrolled IFN[unreadable] alpha release drives unabated activation/maturation of myeloid DCs. We have also found that IFN-alpha is a[unreadable] powerful inducer of plasma cell differentiation and survival possibly contributing to the[unreadable] hypergammaglobulinemia observed in SLE patients. Finally, using global gene expression analyses of SLE[unreadable] PBMCs we have identified clusters of differentially expressed genes i) induced by IFN-alpha. ii) expressed[unreadable] by low density immature and mature neutrophils. We have determined that the expression of neutrophil-specific[unreadable] genes 1) correlates with SLE disease activity, 2) allows to discriminate patients with and without[unreadable] lupus nephritis (LN), and 3) predicts the development of LN. These data support that neutrophils play an[unreadable] important role in the pathogenesis of SLE and in the induction of renal disease.[unreadable] Therefore, the goals of the present application are to i) further define the role of neutrophil-encoded[unreadable] transcripts and proteins as markers of disease activity and predictors of response to therapy, ii) to identify[unreadable] the serum factors responsible for the activation/apoptosis of SLE neutrophils, iii) to determine whether[unreadable] neutrophils represent a source of self-antigens for dendritic cells to be presented to T cells and drive[unreadable] autoimmune responses, and iv) to establish the direct role of neutrophils in kidney pathology. Ultimately[unreadable] these studies will further our understanding of SLE pathogenesis and help us develop better therapies to[unreadable] treat SLE patients.