2008 Biomarkers, Human Lupus Biology
2013 Biomarkers, Central Nervous System, Human Lupus Biology
LRI Class of 2013
Novel Insights into Cerebral Lupus
The Study and What It Means to Patients
“We are applying the state-of-the-art technology in a comprehensive search for biological indicators (biomarkers) that can improve the diagnosis and treatment of lupus.”
Many lupus patients will experience nervous system complications such as memory loss, seizures and problems with perception and reasoning. But there are currently no lab tests to accurately diagnose neuropsychiatric lupus or predict who is most at risk for particular complications. We are using cutting-edge technology to identify antibodies and chemicals in the blood and cerebrospinal fluid of lupus patients that could form the basis of a future biological lab test (biomarker) for lupus of the central nervous system.
Current diagnosis, classification and sub-setting of neuropsychiatric lupus are far from optimal given that there are currently no molecular criteria for achieving this. None of the laboratory or radiographic tests currently reported is sensitive and specific in establishing the diagnosis of NPSLE. Currently we have no way of predicting which NPSLE patients might progress to manifest particular neuropsychiatric symptoms. The current proposal aims to tackle the above challenges, building upon a panel of novel autoantibody and metabolic markers we have recently identified, using comprehensive profiling tools. A combination of cross-sectional and longitudinal studies will be used to ascertain if the levels of these novel markers in the serum or cerebrospinal fluid could help predict neuropsychiatric events in cerebral lupus.
LRI Class of 2008
LRI Class of 2008 Consortium Grant with Chaim Putterman, MD, at the Albert Einstein College of Medicine in the Bronx.
Lupus nephritis is common in people with lupus, and can cause irreversible kidney damage. The need for biomarkers (“early predictors”) to detect problems and monitor treatment effectiveness is urgent.
Working collaboratively under a consortium grant from the Lupus Research Institute, Drs. Putterman and Mohan have been investigating biomarkers to develop non-invasive tests to diagnose and monitor kidney damage from lupus. Their animal study identified four proteins that show up in urine in increasing quantities as kidney damage progresses. Each of these proteins is either present in humans or has a human equivalent. Based on the success in these studies, the researchers currently are studying whether an increase in the levels of these proteins also indicates an increase in disease among lupus patients.
“With LRI funding, we are now conducting tests in humans, using the urine of people with lupus to determine the value of these proteins as biomarkers or indicators of disease severity,” commented Dr. Putterman. “If we can predict flares when patients’ symptoms suddenly worsen and monitor their response to treatment, we can better manage their disease.”
Some of Dr. Mohan’s collaborative work with Dr. Putterman in this area is described here:
Urine Proteome Scans Uncover Total Urinary Protease, Prostaglandin D Synthase, Serum Amyloid P, and Superoxide Dismutase as Potential Markers of Lupus Nephritis. J Immunol. 2010 Published online January 11. Wu T, Fu Y, Brekken D, Yan M, Zhou XJ, Vanarsa K, Deljavan N, Ahn C, Putterman C, Mohan C.
Strain distribution pattern of susceptibility to immune-mediated nephritis. J Immunol. 2004 172(8):5047-55. Xie C, Sharma R, Wang H, Zhou XJ, Mohan C.
Enhanced susceptibility to end-organ disease in the lupus-facilitating NZW mouse strain. Arthritis Rheum. 2003 48(4):1080-92. Xie C, Zhou XJ, Liu X, Mohan C.