Impact of the SLE Gene BANK1 on Autophagy and Plasmablast Differentiation in Lupus
Abstract
Lupus is a chronic autoimmune disease affecting the skin, joints, and internal organs including kidney, brain, heart, and lungs. It affects up to 1.5 million Americans and is estimated to affect at least 50,000 Veterans. The studies proposed in this application address the FY17 LRP Focus Area of understanding lupus disease variability and underlying disease process in relation to genetic predisposition. Although it is well established that SLE is an autoimmune disease, the underlying mechanisms that result in the production of self-reactive antibodies that are critical for the development of lupus are not completely understood. The studies proposed here will address this challenge by determining how the intersection of two pathways, autophagy and plasma cell development, can promote the production of these destructive antibodies, and how a gene, BANK1, linked to the development of SLE, influences this process. The project will use blood samples from both individuals with SLE and healthy people with or without the BANK1 SLE risk gene variants to study the link between the autophagy and plasma cell pathways and the effect of the BANK1 gene. We will also use cutting-edge genetic engineering methods to model the BANK1 SLE risk gene variants in human cells to study their effect on these pathways. Additionally, the proposed studies will test drugs that target the autophagy pathway to determine if they can block the plasma cell pathway and antibody production using in vitro assays with blood samples from healthy people and SLE patients. The short-term impact of the proposed study is that it will advance understanding of the development and progression of SLE. It will also provide insight into how genetic risk affects a patient’s response to therapy. The long-term impacts include improved diagnosis, personalized treatment approaches, and identification of new directed therapies for SLE. These outcomes will improve the diagnosis and care of active military personnel and Veterans with lupus, and will offer insight into individuals at risk for developing SLE and possible interventions to prevent development of disease.
Document Details
- Document Type
- DoD Grant Award
- Publication Date
- Oct 29, 2018
- Source ID
- W81XWH1810596
Entities
People
- Karen Cerosaletti
Organizations
- Benaroya Research Institute
- United States Army