A Novel Imaging Agent for Detecting and Monitoring Lupus Nephritis
Abstract
Rationale, Objective, and Aims. This is a project to develop methods for detecting and monitoring inflammation in patients with systemic lupus erythematosus (SLE). SLE is an autoimmune disease that can affect multiple different organs, including the kidneys, heart, intestine, and central nervous system. SLE is a lifelong disease marked by flares and remissions. The treatment of SLE almost always includes medicines that suppress the immune response. These drugs reduce tissue inflammation and injury, and the mortality for patients with SLE has improved in recent decades. Aggressive and prolonged immunosuppression reduces – but does not eliminate – the risk of future flares. Consequently, even patients who have remained in remission for prolonged periods need to continually be monitored for evidence of a disease flare, and these flares usually require patients to restart treatment. However, the immunosuppressive drugs currently available also have many side effects. Most importantly, these drugs increase patients risk of infections. Treatment, therefore, should be minimized in patients who are in remission and do not have active tissue inflammation. The effects of SLE differ from patient to patient. Furthermore, in individual patients the manifestations change over time. Given the unpredictable course of SLE progression and the side effects associated with treatment, SLE is plagued by many of the same difficulties that make the treatment of cancer so challenging. As in many cancers, for example, the severity of each patients lupus must be continually weighed against the toxicities of the therapies used to treat the disease. Patients with clinically silent disease may benefit from treatment, but the duration of treatment depends upon the individual patients response. Given these difficulties, new methods of measuring disease activity are desperately needed. Significant effort has been expended to discover new markers that clinicians can measure to determine whether patients need to be treated or are in remission. Several lab tests are helpful for monitoring disease, but none of these tests is sufficiently accurate to guide physicians as to whether patients need more treatment or can have their treatment discontinued. Because of the limited utility of these tests, the definitive diagnosis of activity within a specific tissue requires a tissue biopsy. Biopsies are invasive procedures that put patients at risk of bleeding and infection. Furthermore, it may not even be feasible to biopsy some organs, such as the brain and spinal cord. Thus, non-invasive methods of detecting active SLE within specific organs would be of great clinical utility. This is a project to develop a method of monitoring lupus disease activity. Relationship of this work to specific Focus Areas of this Program Announcement. This project will address several FY2018 LRP focus areas. It will provide an imaging tool for assessing disease heterogeneity among patients by quantifying inflammation within tissues. It is expected to provide a new method for monitoring the progression of lupus nephritis over time. This method is expected to enable clinicians to personalize each patients treatment based on their disease severity and their response to treatment. Applicability of the research. The imaging methods that we are developing in this project offer the possibility of non-invasively detecting tissue inflammation in patients with lupus. It will allow clinicians to: (1) more accurately identify which patients with SLE need to be treated with immunosuppressive drugs, and (2) determine whether immunosuppressive treatment of these patients is effective. These imaging methods will provide the same information that can currently be obtained only by an invasive tissue biopsy. Furthermore, biopsies sample only a small portion of tissue, and these imaging methods will report on inflammation throughout the whole organ and throughout the entire body. Because t
Document Details
- Document Type
- DoD Grant Award
- Publication Date
- Nov 19, 2019
- Source ID
- W81XWH1910717
Entities
People
- Joshua Thurman
Organizations
- United States Army
- University of Colorado Denver