The basic biological mechanisms that underpin autoimmune disorders are finally coming to light. Researchers in Boston’s Longwood medical area — a neighborhood where the streets are flanked by hospitals, research institutions and academic centers — are setting the stage for a new wave of future therapies that can prevent, reduce or even reverse symptoms of disease.
Inside the lab of Michael Carroll, PhD, scientists are working to understand how and why immune cells start to attack the body’s own tissues; it turns out the immune system’s B cells compete with each other in true Darwinian fashion. On the way to this discovery, the lab has flushed out new potential drug targets that could ease autoimmune symptoms — or stop them entirely — by “resetting” the body’s tolerance to itself.
The implications for a link between inflammation and synapse loss go beyond lupus because inflammation underpins so many diseases and conditions, ranging from Alzheimer’s to viral infection and even to to chronic stress. In which case, are we all losing synapses to some varying degree? Carroll plans to find out.
“We’ve found that chronic inflammation and autoinflammatory disorders can originate from genetic mutations to MDA5 that cause it to misrecognize ‘self’ as ‘non-self,’ essentially launching the immune system into self-attack mode,” said Hur. …
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. …
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’s 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.…