Lupus Symptoms Linked To Inflammation In The Brain

Active type 1 interferon receptor signaling observed (green) within the brain (red). Boston Children's Hospital

Lupus is a life-long autoimmune disease that can attack almost any organ in the body, including the heart, lungs, and brain. Yet the cause behind many of its neurological symptoms is still a mystery to scientists.

"In general, lupus patients commonly have a broad range of neuropsychiatric symptoms, including anxiety, depression, headaches, seizures, even psychosis," said Allison Bialas, first author of a new study, in a statement. "But their cause has not been clear."

The mystery lies in the fact that the blood brain barrier is highly selective – only specific substances are allowed through to protect the brain from harm. This has caused scientists many headaches over the years, as the brain’s high-end security system often also prevents them from providing life-saving drugs.

For lupus, the question is what is getting through this barrier?

Scientists have known for some time that lupus causes the patient’s immune system to attack the body’s tissues and organs. This results in white blood cells releasing proteins called type I interferons, which act like an alarm bell for the rest of the immune system. 

But these proteins don’t cross the blood brain barrier – so why the inflammation in the brain?

"There had not been any indication that type 1 interferon could get into the brain and set off immune responses there," said senior author Michael Carroll, whose study is published in the journal Nature.

You can imagine his surprise then when they discovered that these pesky interferons could indeed infiltrate the blood brain barrier. This led the microglia – immune defense cells – to attack the ever-so-important synapses in the brain. 

"We've found a mechanism that directly links inflammation to mental illness," said Carroll. "This discovery has huge implications for a range of central nervous system diseases."

Synapses are the junction at which neurons pass electrical or chemical signals to each other. nobeastsofierce/Shutterstock

The team, however, did not stop there. In order to test the veracity of their findings, they administered a drug that blocks the type 1 interferon receptors. This seemed to do the trick: It prevented synapse loss in mice with lupus compared to those not given the drug. 

The mice given the drug also displayed less behavioral signs associated with mental illness, such as anxiety and cognitive defects. 

The importance of this research cannot be understated. Around 1.5 million Americans have a form of lupus, according to the Lupus Foundation of America, and the majority of these are women.

The discovery will hopefully provide a basis for future trials to investigate the drug’s effects on lupus and other central nervous system diseases in humans, including Alzheimer’s, viral infection, and even chronic stress.

"We've seen microglia dysfunction in other diseases like schizophrenia, and so now this allows us to connect lupus to other CNS diseases," says Bialas. "CNS lupus is not just an undefined cluster of neuropsychiatric symptoms, it's a real disease of the brain – and it's something that we can potentially treat.”

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