Immunoglobulins and Efgartigimod dampen neuronal activity in rat cortical cultures

Immunoglobulin-based therapies are widely used to treat neuroinflammatory diseases, but whether they act directly on nerve cells has remained an open question. A new proof-of-concept study from the University of Cologne, published as a Brief Research Report in Frontiers in Cellular Neuroscience, suggests that they can. Working with primary rat cortical neuron cultures, the researchers found that these neurons express two Fc receptors—the inhibitory Fc gamma receptor IIb (FcγRIIb) and the neonatal Fc receptor (FcRn)—and that both immunoglobulin treatment and the FcRn blocker Efgartigimod were associated with reduced neuronal activity in the dish.

The team first established receptor expression using immunocytochemistry and mRNA analysis.

To test whether these receptors matter functionally, the researchers used microelectrode array recordings to measure neuronal activity in the cultures. When the cultures were treated with immunoglobulins, neuronal activity dropped both under physiological conditions and under inflammatory conditions. The study found that immunoglobulin treatment reduced neuronal activity under both physiological and proinflammatory conditions, and that FcγRIIb expression was upregulated under proinflammatory conditions.

Under control conditions the observed effects suggested a trend toward dose dependence, although the authors characterize this as a trend rather than a firmly established dose-response relationship. The parallel effects of immunoglobulins and Efgartigimod are consistent with the idea that Fc receptor signaling in neurons could mediate the response, but the study is explicitly framed as proof of concept in vitro.

The authors are careful about scope. The work was carried out in primary rat cortical neuron cultures, not in living animals or patients, and the abstract presents the receptor findings as evidence obtained by immunocytochemistry and mRNA analysis rather than as demonstrations of mechanism. The reduction in activity is reported as an observed association with treatment; the study does not establish how the receptors transduce the signal or what the changes mean for network function beyond the recorded activity. The authors position neuronal Fc receptor signaling as a promising avenue for future studies rather than as a validated therapeutic target.

Even with those limits, the result is striking because it shifts attention from immune cells to neurons as possible direct responders to immunoglobulin-based drugs. Confirming that will require follow-up work in more complex systems, but this culture-based study provides the initial evidence that the machinery—and a measurable functional response—is present in cortical neurons.

Subject of Research: Fc receptor expression in rat cortical neurons and reduced neuronal activity after immunoglobulin and Efgartigimod treatment

Article Title: Immunoglobulins and Efgartigimod reduce neuronal activity in primary rat cortical neuron cultures

Article References: Marti Bautista, F., Nazarzadeh, N., Genseke, N., Groß, E., Olschewski, D. N., Fink, G. R., Schroeter, M., Rueger, M. A., & Vay, S. U. (2026). Immunoglobulins and Efgartigimod reduce neuronal activity in primary rat cortical neuron cultures. Frontiers in Cellular Neuroscience, 20, Article 1939772. https://doi.org/10.3389/fncel.2026.1939772

Image Credits: AI Generated

DOI: 10.3389/fncel.2026.1939772

Keywords: FcγRIIb, FcRn, Efgartigimod, immunoglobulin therapy, cortical neurons, microelectrode array, neuroinflammation, in vitro, rat neurons, Fc receptors, neuronal activity, Immunoglobulins