Breaking Through – Uncovering a Probable Cause of Lupus:
Breaking Through – Uncovering a Probable Cause of Lupus:

December, 2018

An innate — and lifelong — curiosity about the most complex, unresolved questions in medicine has served John D. Mountz, MD, PhD, from the University of Alabama at Birmingham, Division of Clinical Immunology and Rheumatology, well.

For the past three decades he has made significant strides in piecing together some of the most disparate aspects of lupus — greatly advancing the molecular understanding of this disease for the entire lupus community.

With so many fundamental gaps in our understanding of lupus, Dr. Mountz’s current work aims high. He is looking to uncover a root cause of lupus with a major grant he received from the Lupus Research Alliance.

Dr. Mountz is pursuing an innovative research investigation that focuses on interferon-beta. He seeks to prove that it sets off a chain of events that triggers an inflammatory response and destructive mechanisms that can lead to advanced disease in patients.

Why interferon beta? It is the most potent of all 13 interferons, the class of protein molecules used to trigger the protective defenses of the immune system that help eradicate pathogens.

In his work, Dr. Mountz has found that patients with high levels of this molecule in the early development of B-cells are more likely to have higher levels of autoantibodies and kidney disease. He hopes his study of interferon-beta will explain how lupus develops and why some people are at greater risk for flares and kidney disease.

Another interesting fact about interferon-beta is that African-Americans with lupus have higher levels of it in their cells compared with Caucasians with lupus.

“If we can figure out why interferon-beta is produced, why it is high in lupus patients, and what it does to promote B-cell tolerance loss and autoantibody production — we are going to have major clues. And, of course, if it is interferon-beta, well, the solution is obvious — block it,” Dr. Mountz said with authoritative zest.

Going back to an earlier point, if interferon-beta is expressed in the early development of the B-cells, it does two things. “There are B-cells that produce interferon beta and B-cells that respond to interferon beta,” said Dr. Mountz. “So the ones that produce it probably produce it both for themselves and for other B-cells in the environment. But interferon-beta also has an effect on itself, due to the interferon signaling pathway in the DNA of the B-cell.”

In this scenario, if a patient produces a B-cell or a group of B-cells that have a lot of interferon, the trajectory of those B-cells is changed forever. Because it imprints on the chromatin, those B-cells are more susceptible to interferon. The chromatin is a complex of macromolecules found in cells, consisting of DNA, protein, and RNA.

“Inhibiting interferon-beta at the right time and with the right people might inhibit disease progression and even induce tolerance,” he continued. “The patient might not have to receive the therapy forever — just long enough to cause tolerance, to re-stabilize or normalize their immune system that went off track.”

The Lupus Research Alliance is eager to see the outcome of this investigation. If Dr. Mountz is correct in his assumption, doctors may finally have the ability to keep lupus at bay for a large percentage of people who have the disease.

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