Chandra Mohan, MD, PhD
University of Texas Southwestern Medical Center, Dallas, TX
2013 Central Nervous System
2013 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.”
The consortia, a powerful pooling of talent and technology that the LRI was willing to consider for ‘human lupus biology’ research, will also study the value of these biomarkers in monitoring and measuring response to therapy. By using human tissue—in this case, urine from people with lupus—the investigators are more likely to make discoveries directly relevant to humans.
If successful, the study could represent a major breakthrough with potentially immense impact on better managing lupus nephritis.
Some of Dr. Mohan’s collaborative work with Dr. Putterman in this area is described here:
LRI Class of 2006
In 2006, Dr. Mohan received a Novel Research Grant from the LRI to pursue a novel idea in lupus genetics.
The genes a person inherits may make him or her more susceptible to lupus, and the LRI funds various research endeavors to explore this association, so that measures can be taken to anticipate or modify it.
Dr. Mohan noted that under normal circumstances, genes patrol B-cell tolerance checkpoints to curb autoimmune reactions. But it’s still unclear which genes these are. So Dr. Mohan set out to use a newly established method of screening for these genes that involves activating a substance dubbed “sleeping beauty” that can “cut and paste” a mobile sequence of DNA into random locations within B cells.
Dr. Mohan’s work has the potential to reveal invaluable information on the spectrum of molecules able to alter B-cell tolerance and participate in causing the destruction of lupus, and point to new targets for drug therapies.
A summary of Dr. Mohan’s ongoing lupus research and a more extensive list of recent publications can be found at http://www4.utsouthwestern.edu/mohanlab/ or http://www.utsouthwestern.edu/utsw/cda/dept20539/files/131854.html.
LRI Class of 2001
With an LRI grant in 2001, Dr. Mohan investigated the hypothesis that lupus-prone mouse strains have a genetically determined sensitivity to kidney damage that is independent of their genetic predisposition to produce autoantibodies.
His tests could help identify lupus patients at risk for kidney damage and also provide clues to treatments to prevent such damage.
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.
In 2003, Dr. Mohan won a $940,000 NIH grant to continue working on his LRI-funded work, “Immunogenetics – Target Organ Damage in Immune Nephritis.”
Rev. January 2013
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- B Cells
- Cardiovascular System
- Cell Signaling
- Central Nervous System
- Dendritic Cells
- Environmental Triggers
- Gender Matters
- General Immune System Function
- Human Lupus Biology
- Lupus Pregnancy
- New to Lupus
- New Treatments
- T Cells
- Target Identification
- Why the Lupus Immune System Reacts to Its Own DNA