Dogs and humans share many diseases. Bone cancer and brain tumors behave similarly in both species, as do several autoimmune disorders. These similarities make bridging research on canine and human medicine critical to finding cures—and preventing disease—in both humans and their best friends.

Autoimmune hemolytic anemia (AIHA) is an autoimmune disease that occurs at much higher rates in dogs than in people, but the disease looks the same in both species. It usually comes on quickly and causes the immune system to develop proteins called autoantibodies that attack the body’s own red blood cells. When autoantibodies destroy enough red blood cells, both people and dogs become anemic and develop a host of complications.

One key difference between AIHA in humans and dogs is that in humans, AIHA is a relatively rare disease. Studies suggest that the disease occurs about 10 times as often in dogs as it does in humans. In certain breeds, mainly cocker and springer spaniels, the disease may be even more common—upwards of 100 times more common than in humans.

“In humans, it’s a very rare disease, so it’s hard to study because recruiting enough patients to really learn about the disease is challenging,” says Steven Friedenberg, an associate professor in the Department of Veterinary Clinical Sciences at the College of Veterinary Medicine (CVM).

A $2.9 million grant from the National Institutes of Health (NIH), will allow Friedenberg to home in on the genes that cause AIHA in dogs, which may be similar to those that cause the disease in humans. Using a canine model might be key to deepening what doctors and drugmakers understand about the underlying causes of AIHA in people. Understanding how the disease occurs may give scientists a roadmap to find cures that prevent the immune system from attacking healthy cells.

Although researchers have developed mouse models to study AIHA, “no one has really studied this disease so extensively in a naturally occurring model,” Friedenberg says.

Preventing onset

The research has two main goals. In the first, Friedenberg, who holds a PhD in genetics, is collaborating with Leigh Anne Clark, a canine geneticist at the University of Georgia.

“We don’t know very much about the genes that cause this disease in either humans or dogs,” Friedenberg says, so the first part of this research will be mapping genes in dogs with AIHA to identify which may be responsible for the disease.

“These findings will help us understand more about the pathogenesis of the disease,” Friedenberg says. “We don’t exactly know why this disease happens.”

In about 80 percent of dogs with AIHA, scientists do not have a clear-cut understanding of why the disease occurs. Those cases are likely caused by a genetic predisposition, which is why Friedenberg is focusing on this aspect of the disease first.

For the second part of his research, Friedenberg will draw on his expertise in immunology. During his first five years as a faculty member at the University of Minnesota (UMN), Friedenberg was awarded an NIH K Award, which helps faculty get additional training in areas that may help their career.

During those years, Friedenberg took a One Health approach, learning everything he could about immunology through collaborations with researchers at UMN Medical School’s Center for Immunology. His focus was on dog T cell biology, which is also the focus of the second part of his new NIH grant.

“Based on mouse models and studies of the disease in humans, we think that T cells, a type of immune cell, are key players in the pathogenesis of this disease,” Friedenberg says.

He’s once again partnering with Marc Jenkins, a Regents and Distinguished McKnight University Professor with the Center for Immunology, and Thamotharampillai Dileepan, an assistant professor in the Department of Microbiology and Immunology, to study what changes in T cell biology might trigger AIHA.

This phase will only focus on cocker spaniels, since this breed has little variation in certain genes that are important in immune system function.

“The limited diversity in these genes makes the T cell biology easier to study,” Friedenberg says. “We hope that what we find from this part of our research will give us an opportunity to intervene early on and train the immune system not to attack itself.”

Figuring out how to prevent an AIHA-predisposed immune system from attacking itself is cutting-edge research. Today, in both people and dogs, AIHA can only be tamped down after the autoimmune reaction starts, typically with immunosuppressive drugs, which have many severe side effects.

“If we can understand the T cell biology that triggers AIHA, we may be able to intervene and prevent the disease from starting,”  Friedenberg says. “And because of the close parallels between dogs and people, what we learn here can help both species—a real One Health opportunity.”