# Autoimmune Encephalitis - Ataxia and Psychiatric Disease: Identifying and Characterizing Novel Antibody Targets

> **NIH NIH R01** · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · 2022 · $767,107

## Abstract

Inflammatory and infectious causes of encephalitis affect 20,000 people a year in the US. More than 50%
of patients have inflammatory disorders requiring prolonged treatment with expensive and dangerous biological
or immunosuppressive agents. The most common identifiable causes of these syndromes are paraneoplastic,
post-infectious or associated with other underlying autoimmune diseases; however, the majority of patients are
still classified as idiopathic. In the last 1-2 decades many of these syndromes have been shown to be associated
with anti-neural autoantibodies that either cause the pathophysiology or serve as critical biomarkers. The most
widely cited examples of these are anti-Hu antibodies, which are highly correlated with an underlying cancer,
and anti-NMDA receptor antibodies, which cause psychosis, seizures and memory disturbances.
 Over the past 5 years, a unique interdisciplinary team of neurologists and basic scientists at UCSF was
formed to develop and deploy an integrated approach to rapidly identify anti-neural antibodies associated with
encephalitis, with the explicit intent to discover and validate clinically actionable biomarkers in addition to
uncovering the fundamental mechanisms of disease pathogenesis underlying these syndromes. The
centerpiece of these efforts is a patient cohort being collected at UCSF called the NID (Neuroinflammatory
Disease) cohort, consisting of patients with suspected infectious or inflammatory encephalitis. This cohort is
now >1,200 patients referred by clinicians at UCSF and from other centers around the world. Already, this
cohort has yielded a new paraneoplastic autoimmune syndrome with important implications for men with
seminoma. More importantly, we have reason to believe this to be just the tip of the iceberg. Our preliminary
data indicates that at least 20% of these patients have associated high titer antibodies in their CSF reactive to
neural antigens in mouse brain. Here, we propose to pursue the hypothesis that a plurality of
undiscovered autoimmune targets underlie a significant fraction of idiopathic encephalitis cases. Using
our unique clinical and molecular approach and our world class patient collection, we will investigate this
hypothesis through the following specific aims: Aim 1: To stratify and characterize the UCSF 1,200 patient NID cohort for the presence of anti-neural antibodies in CSF. Aim 2: High-throughput phage display screen to identify and validate auto antigens. Aim 3: Produce recombinant human antibodies from patients with autoantibody syndromes and develop animal models to test autoantibody pathogenicity.

## Key facts

- **NIH application ID:** 10338166
- **Project number:** 5R01MH122471-03
- **Recipient organization:** UNIVERSITY OF CALIFORNIA, SAN FRANCISCO
- **Principal Investigator:** JOSEPH L. DERISI
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $767,107
- **Award type:** 5
- **Project period:** 2020-04-16 → 2025-01-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10338166

## Citation

> US National Institutes of Health, RePORTER application 10338166, Autoimmune Encephalitis - Ataxia and Psychiatric Disease: Identifying and Characterizing Novel Antibody Targets (5R01MH122471-03). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10338166. Licensed CC0.

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