# Structural mechanisms of autoimmune diseases targeting cys-loop receptors

> **NIH NIH R01** · UNIVERSITY OF CALIFORNIA, SAN DIEGO · 2024 · $638,821

## Abstract

Project Summary/Abstract
 Autoimmunity against neuronal receptors causes an array of diseases. Cys-loop receptors are a class
of neuronal receptors targeted in autoimmune diseases including myasthenia gravis, autoimmune encephalitis,
and autoimmune autonomic ganglionopathy. Myasthenia gravis is the longest studied; antibodies against the
neuromuscular nicotinic acetylcholine receptor were described in 1974. Autoimmune autonomic
ganglionopathy was first identified in 2000 as being associated with antibodies against the ganglionic nicotinic
acetylcholine receptors. Most recently, autoimmune encephalitis was associated with antibodies against the
related GABAA receptor. Mechanisms underlying autoimmune pathology are poorly understood but are often
attributed to receptor cross-linking and internalization. However, other mechanisms that include direct inhibition
of neurotransmission are increasingly reported. We have access to blood and cerebrospinal fluid from patients
suffering from myasthenia gravis, autoimmune autonomic ganglionopathy, and autoimmune encephalitis. Here
we propose to identify and clone autoimmune antibodies that target Cys-loop receptors. We will examine
functional receptor inhibition by patient-derived antibodies using electrophysiology. We will produce antibody
fragments to determine structures of the antibody-receptor complexes from different autoimmune diseases.
These structures combined with functional interrogation will illuminate conserved and divergent mechanisms of
autoimmune disease in this important protein superfamily. This work will lay the foundation for expansion to
other targets of the Cys-loop receptor family and beyond.

## Key facts

- **NIH application ID:** 10757052
- **Project number:** 5R01NS130831-03
- **Recipient organization:** UNIVERSITY OF CALIFORNIA, SAN DIEGO
- **Principal Investigator:** Ryan E Hibbs
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $638,821
- **Award type:** 5
- **Project period:** 2023-01-01 → 2027-12-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10757052

## Citation

> US National Institutes of Health, RePORTER application 10757052, Structural mechanisms of autoimmune diseases targeting cys-loop receptors (5R01NS130831-03). Retrieved via AI Analytics 2026-05-26 from https://api.ai-analytics.org/grant/nih/10757052. Licensed CC0.

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