Autoimmune Disorders

Identifying Bacteria that May Be at the Root of Autoimmune Disorders

Martin Kriegel, M.D.,Assistant Professor of Immunobiology and Internal Medicine

An autoimmune disease called antiphospholipid antibody syndrome (APS) is more common in women than men, and highly prevalent in patients with other autoimmune disorders that are more common in women, such as lupus. The immune system in APS makes antibodies that lead to the formation of blood clots that can cause stroke, heart attack, deep vein thrombosis and pregnancy-related problems, such as recurring miscarriages or premature birth. While the cause of APS is unknown, patients typically are treated lifelong with anti-clotting medications with adverse side effects that include bleeding. Dr. Kriegel hypothesizes that normally benign bacteria in the digestive tract trigger the production of the harmful antibodies in APS patients. His preliminary data from laboratory work has identified a possible antibody-producing trigger among a vast array of different bacteria.

Now, in what is believed to be the first study to identify such triggers among APS patients, Kriegel will determine which bacteria may be at the root of the disease. His ultimate goal is to identify biomarkers for development of new diagnostic and treatment options to target and stop initiation of the antibodies rather than mitigating the harmful effects of antibodies after production.

Understanding the Causes of Lupus

Mark Mamula, Ph.D.,   Associate Professor of Internal Medicine (Rheumatology)

Systemic Lupus Erythematosus or SLE (often referred to simply as Lupus) is a chronic autoimmune disease that affects tissues and organs throughout the body. Approximately 90 percent of patients with SLE are women, and the disease is most common in women of childbearing age. Dr. Mamula studied how, in lupus, the body targets itself for attack by its own immune system. Identifying the mechanisms that initiate this process is necessary in beginning to devise an intervention that will stop this self-destructive cascade.

Highlighted Study Findings

A major question in understanding SLE is how specific proteins in the body, called autoantigens, become targeted for attack by the immune system. The goal of Dr. Mamula’s work is to identify the specific factors that may trigger this disease. In this study, Dr. Mamula’s research group was able to identify one type of protein that may trigger SLE, thus providing information that begins to uncover the mechanisms important in understanding what starts and maintains diseases of the immune system. A more thorough understanding of the earliest processes in such diseases was an important first step to identify potential targets for treatment of SLE.

Finding the Proteins that Stimulate Lupus

Mark Mamula, Ph.D.,  Associate Professor of Internal Medicine (Rheumatology)

(Collaborator: Bailin Liang, Ph.D., Associate Research Scientist in Internal Medicine (Rheumatology))

Systemic lupus erythematosus (SLE) is a disease of the immune system that primarily afflicts women particularly in the first few decades of life.  Although the specific causes are unknown, SLE is the product of a complex interaction of white blood cells, proteins and body tissues. Dr. Mamula’s study builds on previous work and investigates particular cell surface molecules that lead to production of autoantibodies that lodge in various organs and cause inflammation and tissue damage.

Highlighted Study Findings

A previous program-funded investigation identified one type of protein that may trigger Systemic Lupus Erythematosus or SLE, providing initial information that could be used in the prevention and/or treatment of this disease. In this new Ethel F. Donaghue Women’s Health Investigator Program-funded study, Dr. Mamula investigated key cell signaling pathways believed to play a major role in the immune system attacking such tissues as heart, kidney, skin, and blood vessels. These cell signaling pathways were important to understand because drugs that act on these particular pathways have been used in early clinical trials but are not yet well understood. A more thorough understanding of the cell mechanisms of this disease and the action of drugs that affect the disease will allow the development of more effective interventions. This study represented another key step in this early development.