Dr. Martin Kriegel - Arthritis Research

Researchers on the Path to a Cure – Spotlight on Dr. Martin Kriegel

Trillions of bacteria live in or on your body. There are actually as many bacteria in your body as cells in your body. Fortunately, for most of us, most bacteria that live within us are helpful, not harmful. We call these bacteria commensal bacteria. Dr. Martin Kriegel and his team have been studying these bacteria, and more specifically, a protein that humans and bacteria produce, called Ro60, that plays a role in the development of lupus.

Ro60 is a major target in lupus patients. It is one of the first proteins that antibodies recognize in healthy people who are predisposed to developing lupus. The antibodies to Ro60 can be found years before a person develops lupus. In their 3-year Arthritis Foundation-funded study, “Commensal Prokaryotic Ro60 Orthologs as Causal Trigger for Lupus”, Dr. Kriegel and his team discovered that proteins closely related to the human Ro60 protein are present in several types of bacteria that live in the mouth, gut, and skin of humans. The structure, function, and genetic code of the bacterial Ro60 protein and human Ro60 protein are very similar. When the genetic code for the proteins produced in different species are so similar, we call the genes orthologs.

Dr. Kriegel wants to identify strategies to prevent lupus from happening. Lupus is an autoimmune disease. The body’s immune system usually defends the body against infectious agents and other things that it recognizes as “non-self”. With autoimmune diseases, the immune system is broken and starts to attack “self”. Dr. Kriegel has been studying lupus, and immunity in general, for over 10 years. He wants to understand the how and why of the broken immune response. Why does the immune system no longer tolerate self? Why is “self” versus “non-self” mistaken?

Dr. Kriegel and his team are testing whether the autoimmune response in lupus patients is originally directed against bacterial Ro60 (“non-self”) proteins, but then becomes cross-reactive to human Ro60 (“self”) protein because both types of Ro60 are so similar. To test this, the team is collecting mouth, gut, skin, and blood samples from lupus patients and healthy people. The samples will be tested in the lab to see if the immune systems cross-react with bacterial Ro60 proteins.

According to Dr. Kriegel, an increase of bacteria compared to control subjects is not the important factor. What is important is whether the bacteria are present at all in predisposed people. “If our hypothesis is true,” he explained, “this discovery could have far-reaching implications for public health since an entirely new set of treatments could be developed for lupus and related rheumatic diseases like Sjogren’s syndrome that also targets this protein. The concept that human autoimmunity is triggered through cross-reactivity with proteins made by the bacteria that reside in our own tissues might have applications to other autoimmune diseases that afflict a large portion of the U.S. population.”

Dr. Kriegel is an assistant professor of Immunobiology and Medicine (Rheumatology) at Yale School of Medicine.

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