When “Psychosis” Is Really an Autoimmune Attack on the Brain

Alina Sternberg, a psychiatrist, was abruptly hit with crushing fatigue and brain fog. Neurologists told her the symptoms were caused by depression. Turns out her symptoms weren’t ‘in her head’.

The culprit was an autoantibody in her blood that targeted a brain protein called CASPR2. She “got [her] life back” almost immediately after being treated with intravenous steroids.

There are more like Alina.

Take April Burrell, who lived in a psychiatric hospital for 20 years because her catatonic state left her immobile and unresponsive. Thankfully, after 2 decades, she suddenly woke up when clinicians began treating her for a previously unrecognized autoimmune disease.

How many more patients are trapped in psychiatric hospitals who actually have a treatable form of autoimmune encephalitis?

Dozens of different neuropsychiatric diseases have been identified over the last 15 years, all triggered by an immune attack on the brain, known as autoimmune encephalitis. The consequences of autoantibodies targeting CNS tissue can lead to diverse neurological symptoms, and in some cases, psychosis.

But what if a patient has a brain-attacking autoantibody that is not known to science?

That is where PhIP-seq comes into play.

PhIP-seq technology was developed by Benjamin Larman and colleagues, in collaboration with Stephen J. Elledge’s lab at Harvard Medical School/Brigham and Women’s Hospital.

Years later, the DeRisi Lab at UCSF (including Michael Wilson, Joseph DeRisi, Caleigh Mandel-Brehm, Brian O’Donovan, and others) modified the method to identify novel neurological autoantibody targets in the brain.

Like fishing, this method uses autoantibodies from the patient’s cerebrospinal fluid (CSF) or serum to bind a vast library of over 700,000 human protein fragments localized to the outer surface of viruses that infect bacteria, known as bacteriophages.