# How autoimmune antibodies kindle a firestorm in the brain

## TL;DR

Autoimmune antibodies against brain receptors can disrupt their normal function and cause inflammation, leading to encephalitis.

## Contribution

The study reveals a crossover effect of autoantibodies on receptor localization and function, influenced by neuronal activity and receptor interactions.

## Key findings

- Autoantibodies against NMDARs and GABAARs affect the lateral mobility and localization of these receptors.
- The crossover effect on opposite receptors depends on neuronal activity and interactions with the D1 dopaminergic receptor.

## Abstract

Autoimmune responses against NMDA receptors (NMDAR) and GABAA receptors (GABAAR) can cause encephalitis, which has been described as feeling like one’s brain is on fire (Dalmau et al, 2019). The molecular mechanisms of how the autoantibodies affect neuronal functions are incompletely defined. Hunter et al (2024) now describe effects of autoantibodies from patients against NMDARs and GABAARs on the lateral mobility and thereby localization and function of NMDARs and GABAARs as well as AMPA receptors (AMPARs), the main glutamatergic receptors that mediate basal synaptic transmission. The study provides evidence for crossover effects of autoantibodies on the opposite receptor that depend on neuronal activity and the interaction of NMDAR with the dopaminergic receptor D1.

Patient-derived autoantibodies against NMDARs and GABAaRs show a crossover effect on the opposite receptor’s localization and function dependent on neuronal activity.