With a $4M grant from the National Institutes of Health, a University of Houston pioneer in autoimmune research, Chandra Mohan, is launching a 10-year study set to target the very heart of autoimmune disease – examining what causes the body to attack itself and identifying biological pathways that could become targets for new treatments.
The debilitating array of Systemic Autoimmune Rheumatic Diseases (SARD) includes Rheumatoid Arthritis, Systemic Lupus Erythematosus, Sjogren’s Syndrome and Systemic Sclerosis. All of them are chronic, without a cure, and impact more than 30 million people worldwide.
Inside the human body, the immune system is always on guard, hunting down and killing disease and viruses with mal intent. But often, it stumbles and attacks innocent, non-threatening tissues and organs, resulting in autoimmune disease.
Commonly, it attacks the same culprit: nuclear antigens, which exist within a cell nucleus. This leads to anti-nuclear antibodies initially, and to a wide array of SARDs, eventually.
“Loss of tolerance to nuclear antigens leads to the development of anti-nuclear autoantibodies and is an early phase of SARD, present in more than 50% of patients,” said Mohan, Hugh Roy and Lillie Cranz Cullen Endowed Professor of Biomedical Engineering. “However, the specific genes, risk factors and molecular pathways underlying this early phase of autoimmunity, and subsequent development of rheumatic disease remain unclear.”
Mohan will dissect the triggers, studying blood samples and environmental exposure over a 10-year period.
“Collectively, these studies will help identify the genetic, environmental and cellular factors that are operative at the two steps of SARD development, namely the emergence of anti-nuclear autoantibodies and disease onset. More importantly, these studies will highlight functional molecular pathways and mechanisms that may be operative at each step,” said Mohan.
“Individual SARDs have been examined in silos without an attempt to discern shared underlying features at the molecular level. Current understanding of the initial (and likely shared) origins of SARDs is only rudimentary but urgently needed to develop means for prevention and treatment,” said Mohan.
This study will be carried out in collaboration with Dr. Karen Costenbader at Harvard Medical School, Boston.