Understanding How Your Immune System Affects Your Nerves & Muscles With MG

If you live with myasthenia gravis (MG), you know the feeling: Your muscles grow weak and tired, sometimes for no clear reason. But have you ever wondered what is happening inside your body to cause this? The answer involves 2 key players working together – a part of your immune system called the complement system, and a tiny meeting point between your nerves and your muscles.

What is the complement system?

Your immune system protects you from germs. One of its tools is the complement system. It is a group of more than 50 proteins that float in your blood.¹

These proteins help your body find and destroy invaders like bacteria. They work like a chain reaction. When one protein switches on, it turns on the next, and so on down the line.¹

At the end of this chain, the proteins build a tiny weapon. It is called the membrane attack complex, or MAC. The MAC punches holes in a target cell and destroys it. This is helpful when the target is a germ. But in MG, the system attacks the wrong place.²

The neuromuscular junction: Where nerves meet muscles

To move a muscle, your brain sends a signal down a nerve. The signal travels to a small gap between the nerve and the muscle. This gap is called the neuromuscular junction (NMJ).³

When the signal arrives, the nerve releases a chemical called acetylcholine. This chemical crosses the gap. It lands on special docking spots on the muscle. These spots are called acetylcholine receptors. Once enough of them are filled, the muscle contracts and you move. The process needs plenty of healthy receptors to catch the signal.³

How MG breaks the connection

In most people with MG, the immune system makes a mistake. It creates antibodies that attack the acetylcholine receptors.⁴

With fewer working receptors, the nerve's signal does not get through well, so the muscle becomes weak and tires quickly. This is why MG can cause drooping eyelids, double vision, trouble swallowing, and weakness in the arms and legs. The weakness often comes and goes, getting worse with activity and better with rest.⁴

Complement's role in the damage

The antibodies do not work alone. Most AChR antibodies are types called IgG1 and IgG3. These types are very good at switching on the complement system.⁴

When the antibodies stick to the receptors, they call in complement proteins. The chain reaction begins. The MAC forms right on the surface of the muscle. This breaks down the delicate folds of the junction. It destroys receptors and the structure that holds them in place. Scientists now see this complement damage as a main reason the junction fails in MG.^2,5

A smaller group of patients have a different antibody, against a protein called MuSK. That antibody does not turn on complement well. So complement plays little role in this form of MG.⁶

New treatments that target complement

Complement causes a lot of harm at the junction. So researchers built drugs that block it. These drugs stop a key protein called C5. This keeps the MAC from forming.⁶

Several complement inhibitors are now approved for adults and children who have MG with acetylcholine receptor antibodies. In clinical trials, complement inhibitors reduced muscle weakness. It also improved everyday activities.^6,7

It is worth mentioning that these medicines lower part of your immune defense. So doctors give a vaccine to guard against certain infections before treatment begins.⁶

What this means for you

MG weakness begins at the neuromuscular junction. This is the spot where nerves and muscles connect. Antibodies attack the receptors there. Then the complement system makes the damage worse by building the MAC. Understanding this chain of events helps explain why newer complement-blocking treatments can work so well.^5-7

If you wonder whether these therapies might be right for you, talk with your doctor. Learning how your body works is a powerful first step in taking charge of your MG.