Leading the way to a cure

Lupus Research Update: 2015 Volume 1

Volume 1, 2015 | In This Issue

Critical Hormonal and Microbial Factors Reveal Clues about Lupus >
15 New Studies Funded >
An Innovative Concept + ALR Funding Put New Treatment on the Horizon >
A Sense of Compassion Propels Research - One Physician/Scientist's Perspective >
Mindfulness in Lupus >
Lupus News Corner >


With symptoms varying widely from one patient to the next, lupus is one of the most complex diseases for scientists to decode. Still, there is an irrefutable commonality among patients — most are women.

Michele Kosiewicz, PhD, from the University of Louisville, KY, sees this common characteristic as a great starting point to look for answers.

"There is a strong gender bias in lupus. Women are nine to ten times more likely to develop it than men. Estrogens are known to exacerbate disease — but my focus is a little different: I question why men are protected from disease," said Dr. Kosiewicz.

While this disparity is poorly understood, Dr. Kosiewicz looks to hormones to shed light on the differing susceptibility of the sexes to autoimmune diseases like lupus. Male sex steroids — or androgens — appear to protect men from developing lupus, even men who are genetically predisposed to the disease.

Dr. Kosiewicz wanted to know why.

So, she began looking at recent studies that have shown androgen affects the bacteria that naturally live in the digestive tract — and that these bacteria (gut microbiota), in turn, influence the activities of androgens. One study suggested that the microbiota and androgens might protect males in murine models from autoimmune diseases, such as Type 1 diabetes.

Using a murine model that strongly resembles human lupus, Dr. Kosiewicz's preliminary studies revealed that the microbiota differs between females and males. Even more interesting is the fact that transferring male microbiota to females protects them from disease, i.e. male fecal transplants can protect lupus-prone females from disease.

"We found that when we transfer the male microbiota into females, their tolerogenic dendritic cells improve and we actually see the induction of regulatory T cells that are very important for controlling systemic immune responses, particularly in autoimmune disease," Dr. Kosiewicz explained.

With her ALR-funding, Dr. Kosiewicz has set out to understand how the male microbiota protects against lupus by studying the chemicals — called microbial metabolites — that they produce and their impact on tolerogenic dendritic cells and, ultimately, on disease amelioration. She hopes to discover that these substances, or the entities that produce them, will reveal a pathway to a new treatment option for lupus.

Dr. Kosiewicz is very grateful to the ALR for giving her the opportunity to study the complex relationship between androgens and the gut microbiota in lupus. "The organization has been an invaluable resource for scientists like me, and I'm thrilled that my work can proceed thanks to the funds awarded by the ALR," said Dr. Kosiewicz.

1.5 million

people in the U.S. have Lupus.

172 million

dollars committed to lupus research by the Lupus Research Alliance.

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