A New Study Suggests an Autoimmune Componet to ALS

A recent study published in Nature on October 1, 2025, titled “Autoimmune response to C9orf72 protein in amyotrophic lateral sclerosis,” suggests that ALS has an autoimmune feature. According to Dr. Alessandro Sette, Professor at LaJolla Institute of Immunology, “This is the first study to clearly demonstrate that in people with ALS, there is an autoimmune reaction that targets specific proteins associated with the disease.” 

What’s an Autoimmune Disease

An Autoimmune disease is when your immune system, which is responsible for protecting your body from harmful diseases, starts to turn on itself and attacks parts of your own body. Some of the most well known autoimmune diseases include Type 1 Diabetes. This is where the immune system starts to attack the cells responsible for making insulin in the Pancreas. Another instance is Rheumatoid Arthritis, when the immune system targets the joints in the body, and Multiple Sclerosis when the immune system attacks the central nervous system of the body and disrupts the information from the brain to the rest of the body.

Results of the Study

The study points to a certain type of white blood cell called a Peripheral (meaning outside the brain and spinal cord) CD8+T cells, which circulate outside the brain and patrol the body looking for infected or cancerous cells to kill off. The study suggests that these cells can attack the brain, damaging microglia, and lead to the start of the neurodegeneration process in ALS. They are called “CD8+ because the molecule called CD8 is attached to their surface.

This fits with the growing idea that problems in the immune system, where it gets out of balance or mistakenly attacks the body, might be a key part of how some types of ALS and FTD develop. The study suggests that in some cases, the body’s own immune system may be attacking the brain in a harmful way the same way autoimmune diseases react.

Diseases like Parkinson’s disease (PD) and Alzheimer’s disease (AD) have traditionally not been viewed as involving the immune system attacking the body. In contrast, however, multiple sclerosis (MS) is well-known to involve the immune system attacking the brain, especially through T cells that invade the brain and react against either viruses or parts of myelin (the protective coating around nerves). Newer research suggests that similar immune responses, especially those tied to herpes viruses, may also play a role in Alzheimer’s disease.

The authors of the study state: “This is, to our knowledge, the first study showing the recognition by human T cells of a specific autoantigen associated with ALS. Notably, although the autoreactive T cell response is found broadly in individuals with ALS, it is particularly high in those who are carriers of C9orf72 mutant alleles in classically non-coding regions of the open reading frame.”

T cells- What’s the Difference?

There are two main types of T cells involved in ALS research. CD8+ T cells are the “attackers” and have been found infiltrating the brain in ALS/FTD models and are thought to directly damage support cells like microglia. In contrast, CD4+ T cells, especially a subset called regulatory T cells (Tregs), help maintain immune balance. When Tregs are reduced or not working properly, the immune system can become overactive, which may worsen disease progression. The research supports a growing idea that autoimmune-like reactions, especially involving T cells, may be central to neurodegenerative diseases like ALS. This is a shift from older views that saw such diseases as purely involving “wear and tear” on brain cells without immune involvement.

Treatment Possibilities?

The study indicates new treatments for ALS could be on the horizon for targeting the immune system, especially T cells. Rather than just focusing on neurons themselves and creating vaccine-like or tolerance therapies, and early intervention with identifying this immune signature that may help detect ALS before symptoms fully develop.

Read the press release from the La Jolla Institute

_{Citation: Michaelis, T., Lindestam Arlehamn, C.S., Johansson, E. et al. Autoimmune response to C9orf72 protein in amyotrophic lateral sclerosis. Nature (2025). https://doi.org/10.1038/s41586-025-09588-6}