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It’s not known what triggers the devastating immune malfunction of biliary atresia. The leading theory links it to a perinatal virus infection, which may initiate the progressive, autoimmune attack on the bile duct cells of the liver — an attack against which no defense currently exists. “Biliary atresia accounts for 50 percent of pediatric liver transplants in the United States,” says Cara Mack, MD, a pediatric hepatologist at Children’s Hospital Colorado. It’s far and away the number-one indication.
“For the past 15 years, we’ve been teasing apart the features of the various immune pathways that contribute to bile duct injury,” says Dr. Mack. The root of the problem in biliary atresia is not only the immune system’s destruction of bile duct cells; it’s also the massive scarring that results, and the accompanying blockage of bile flow. Untreated, it would effectively destroy an infant’s liver by 2 years old.
Dr. Mack’s team has made significant inroads into understanding those pathways, specifically the role of T cells, the immune cells that typically identify and destroy infectious agents.
And recently, working with Roberta Pelanda, PhD, an immunologist at the neighboring University of Colorado School of Medicine, they discovered another important player in the biliary atresia immune response: the B cell. Working in the lab with genetically engineered mice, Dr. Mack’s team showed that mice without B cells are protected from biliary atresia. “This tells us that B cells are essential to the onset and progression of bile duct injury in biliary atresia,” says Dr. Mack.
“This new finding — that B cells may be the key to subsequent T cell activation — will open the door to creating new therapeutics.”
The upshot: you can’t genetically engineer babies not to have B cells, but it’s possible that an immune system-modulating compound that targets B cell function may produce a drug that can stop or slow down the progression of biliary atresia.
For now, a liver transplant works well for patients with biliary atresia. But transplantation comes with its own set of challenges — the risk of complications, a lifetime of immunosuppressive drugs, the abbreviated life of the organ itself — aside from the potentially lengthy wait on the transplant list.
“If we can figure out how to treat this disease,” says Dr. Mack, “we can delay or even negate the need for a liver transplant.”
Read about two-year-old Amara Wismann-Espinosa's experience with biliary atresia.