Why Autoimmune Diseases Cause the Body to Attack Itself

A new study published in the journal Cell explores the cellular "runaway train" that allows lupus and other autoimmune diseases to spread throughout the body.

Autoimmune disease is exactly what it sounds like—the body mistakenly fighting itself. This attack may take the form of type 1 diabetes, celiac disease, rheumatoid arthritis, inflammatory bowel disease, or lupus, among others. But what begins as a local problem often eventually goes global.

"Once your body's tolerance for its own tissues is lost, the chain reaction is like a runaway train," co-author Michael Carroll of Boston Children's Hospital and Harvard Medical School said in a statement.

The disease tricks the body into expanding its attack. In a process called epitope spreading, autoantibodies target more and more tissues and organ systems over time, causing new symptoms like joint pain, kidney damage, and severe skin rashes.

To find out how it happens, Carroll and his colleagues zoomed way, way in to examine the progression of lupus in the tissues of lab mice.

"Lupus is known as 'the great imitator' because the disease can have so many different clinical presentations resembling other common conditions," first author Søren Degn, of Boston Children's Hospital and Aarhus University, said in the statement.

"It's a multiorgan disease with a plethora of potential antigenic targets, tissues affected and 'immune players' involved. Lupus is considered a prototypic autoimmune disease, which is why it's so interesting to study."

The researchers used what's called a confetti technique, marking different types of diseased B cells with different colors, then watching the colored dots multiply, scatter, and spread.

The confetti images revealed a microscopic soap opera, as the different colors struggled for dominance and power. As time went on, the makeup of the confetti shifted. One color, or cell type, had won.

Those toxic cells then began converting their neighbors.

"Over time, the B cells that initially produce the 'winning' autoantibodies begin to recruit other B cells to produce additional damaging autoantibodies—just as ripples spread out when a single pebble is dropped into water," Degn said.

The researchers were surprised but excited by their results, which they believe could someday lead to new types of treatment.

"Blocking germinal centers in the midst of an autoimmune response could potentially block the epitope-spreading process," Carroll said. "If you could stop the adaptive immune system for a transient amount of time, it might allow the body to reset its immune responses and shut off the autoreactivity."