Lupus is an autoimmune disease that affects approximately 1.5 million Americans, according to the Lupus Foundation of America. In lupus patients, antibodies that are produced by the immune system’s B cells to protect the body against invading bacteria and viruses also attack the body’s healthy cells.
In November, The Journal of Immunology published lupus research conducted by Chandra Mohan, the Hugh Roy and Lillie Cranz Cullen endowed professor of biomedical engineering at UH Cullen College of Engineering. Mohan’s laboratory identified one particular gene that likely contributes to the onset of the disease.
Several years of genetically crossed mice yielded strains with progressively narrower genetic intervals that still harbored the culprit gene, fatty acid amide hydrolase (FAAH). Through a process of elimination in a mouse model, Mohan and his team confirmed the presence of the gene on mouse chromosome 4 using a microarray analysis technique. Furthermore, they found that FAAH contributes to the B cell polyreactivity in mice with lupus and that levels of the FAAH protein are higher in those abnormal B cells.
To determine whether their findings caused or merely coincided with the disease, they administered a chemical inhibitor that reduced the levels of FAAH in the mice, and they observed that lower levels of the protein corrected abnormalities in the B cells.
Mohan next intends to conduct a study that treats mice with the FAAH inhibitor at the onset of the disease and follows disease progression over time to determine whether or not targeting the protein corrects the disease as it halts abnormal B cell behavior. Ultimately, his goal is to understand the molecular mechanisms of FAAH that cause B cells to make polyreactive antibodies and to conduct similar studies in patients with lupus to ascertain whether or not FAAH also plays an important role in the human disease.
“We know it shuts down the B cell problems in mice with lupus, but we don’t know at this point whether or not that is good enough to treat the disease in mice or humans,” Mohan said.
Mohan’s lupus research may also apply to other autoimmune diseases such as rheumatoid arthritis, multiple sclerosis and irritable bowel syndrome that involve polyreactive antibodies or FAAH. Preliminary studies show that researchers can target FAAH in mouse models for some of these conditions.
Simanta Pathak, a post-doctoral scientist at the UH Cullen College of Engineering, conducted these studies in Mohan’s laboratory, and their ongoing work aims to further unravel the complex molecular networks that lead to lupus.