Stories about: lupus

Finding what fuels the “runaway train” of autoimmune diseases

Competing B cells, pictured here, produce autoantibodies that contribute to autoimmune disease
Natural selection on a small scale: Immune cells called B cells battle each other to produce the best antibody. Here, green represents the B cells that are producing the “winning” antibody, which stamp out competing B cells (other colors). Credit: Carroll lab

A newly-unveiled discovery, four years in the making, could change the way we look at autoimmune diseases and our understanding of how and why immune cells begin to attack different tissues in the body.

“Once your body’s tolerance for its own tissues is lost, the chain reaction is like a runaway train,” says Michael Carroll, PhD, of Boston Children’s Hospital and Harvard Medical School (HMS). “The immune response against your own body’s proteins, or antigens, looks exactly like it’s responding to a foreign pathogen.”

A team led by Carroll has spent years investigating mouse models of lupus to better understand the ins and outs of autoimmune diseases. Its latest findings, published in Cell, reveal that rogue B cells — immune cells that produce antibodies and program the immune system to attack certain antigens — can trigger an “override” that launches the body into an autoimmune attack. Adding insult to injury, B cells’ immune targeting instructions can rapidly expand to order an attack on additional tissue types within the body.

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A surprising new link between inflammation and mental illness — and a potential drug to protect the brain

A synapse being attacked by microglia, which causes neuropsychiatric symptoms in lupus
In the brain, a synapse (red – see diagonal “spine” across center of photo) is seen being wrapped around and attacked by immune cells called microglia (green), leading to synapse loss. Credit: Carroll lab / Boston Children’s Hospital

Up to 75 percent of patients with systemic lupus erythematosus — an incurable autoimmune disease commonly known as “lupus” —  experience neuropsychiatric symptoms.  But so far, our understanding of the mechanisms underlying lupus’ effects on the brain has remained murky.

“In general, lupus patients commonly have a broad range of neuropsychiatric symptoms, including anxiety, depression, headaches, seizures, even psychosis,” says Allison Bialas, PhD, a research fellow working in the lab of Michael Carroll, PhD, of Boston Children’s Hospital. “But their cause has not been clear — for a long time it wasn’t even appreciated that these were symptoms of the disease.”

Collectively, lupus’ neuropsychatric symptoms are known as central nervous system (CNS) lupus. Their cause has been unclear until now.

Perhaps, Bialas thought, changes in the immune systems of lupus patients were directly causing these symptoms from a pathological standpoint. Working with Carroll and other members of his lab, Bialas started out with a simple question, and soon, made a surprising finding – one that points to a potential new drug for protecting the brain from the neuropsychiatric effects of lupus and other diseases. The team has published its findings in Nature.

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