October 4, 2018
Abnormal immune cells invade the kidneys in patients with lupus and can damage the organs so severely that they stop working. But the kidneys defend themselves from these attacks by disabling these rogue cells, according to a new study from two scientists funded by the Lupus Research Alliance. Cancerous tumors similarly protect themselves from the immune system, and the study suggests that the kidneys may use one of the same tricks. The work also identifies two potential new approaches for treating lupus.
Leading the team that made the discovery were Mark Shlomchik, MD, PhD, and his colleague Jeremy Tilstra, MD, PhD, both of the University of Pittsburgh School of Medicine in Pennsylvania. The study builds on work begun by Dr. Shlomchik with his Lupus Insight Prize in 2013. Dr. Tilstra’s 2018 Novel Research Grant from the organization will allow the research to advance further.
The researchers were investigating a condition called lupus nephritis that affects about half of patients with the disease. In these people, the immune system attacks the kidneys, causing inflammation and ultimately organ damage and dysfunction. Researchers have found that in lupus, immune cells known as T cells invade the kidneys; they previously assumed that these T cells were causing harm. But when Drs. Shlomchik and Tilstra analyzed T cells from the kidneys of three different types of lupus-prone mice, they found that these cells instead appeared to be worn out. These “exhausted” T cells had a sluggish metabolism, divided slowly, and produced less of the molecules that stimulate inflammation. By tiring out and disabling the T cells, the kidneys may reduce the amount of damage these immune cells cause.
“We believe this study alters our fundamental understanding” of how lupus leads to kidney damage,” says Dr. Shlomchik.