Revolutionizing the Diagnosis of Autoimmune Diseases

Joseph DeRisi, PhD; Samuel Pleasure, MD, PhD; and Michael Wilson, MD
2016 - 2019 UCSF Weill Innovation Award

“We can now identify the singular cause of any infection – viral, bacterial, parasitic, or fungal – a development that has led to lifesaving diagnoses for patients.” Michael Wilson, MD

Small questions don’t hold much appeal for Drs. Samuel Pleasure and Michael Wilson, Department of Neurology, and Joseph DeRisi, Department of Biochemistry and Biophysics. The talented trio is much more interested in tackling the really big problems, like getting to the root of the mysterious and sometimes deadly illnesses that puzzle even the most seasoned clinicians.

Perhaps it’s no surprise that Drs. DeRisi, Pleasure, and Wilson’s latest project is especially ambitious. Together, they aim to develop a single test to diagnose any form of autoimmune encephalitis – a category of illness characterized by brain inflammation that is notoriously difficult to detect. The first-line test could be integrated into hospitals around the country, helping clinicians garner a diagnosis within 24 to 48 hours.

The foundation for this work: “Along with other colleagues at UCSF, we’ve collected samples from hundreds of patients with mysterious causes of brain inflammation. Using a sequencing test developed by the team, we can now identify the singular cause of any infection – viral, bacterial, parasitic, or fungal. This development has led to lifesaving diagnoses for patients.” Michael Wilson

Some patients remain a mystery: “Three or four times a month, we get a patient who has something that absolutely no one understands. Many of these patients are on a multitude of anti-infective drugs – antivirals, antibacterials – really everything but the kitchen sink. They come to us because they have nowhere else to turn.” Samuel Pleasure

A tool to change it all: “What we don’t have is a tool that lets us say, ‘Well, it’s not infectious, it’s clearly autoimmune, and it’s B-cell driven’ or ‘It’s T-cell driven.’ A diagnostic test could be used in the clinic to guide a patient down one treatment path or another. If you know what you’re dealing with, you can make smart clinical decisions more quickly and ensure better outcomes for patients.” Samuel Pleasure

How the test might work: “We would use sequencing and antibodies from the patients’ cerebrospinal fluid to search for gene expression patterns and antibody reactivity that would help categorize whether the patient is suffering from an infectious or autoimmune process.” Samuel Pleasure

Why philanthropy matters: “It makes our work go at a much faster pace, and it obviates the lengthy – and sometimes completely unnecessary – cycle of grant applications and review. This kind of work is risky, but its impact is potentially huge.” Joseph DeRisi

Why do this work at UCSF: We have a unique structure here that really blends basic sciences and clinical science. The departmental labels don’t mean much here, and the artificial barriers that traditional departmental structures create are absent. We’re also all physically close. There are three or four departments housed in my work neighborhood alone.” Joseph DeRisi