Guillain-Barré syndrome is a rare disease in which the immune system attacks the peripheral nerves. Those affected suffer from muscle weakness and paralysis. A research team led by ETH Zurich has now elucidated the mechanism of this autoimmune reaction.

Patients with Guillain-Barré syndrome (GBS) suffer from a rare and diverse disorder of the peripheral nervous system. The disease is often triggered by previous infections and can lead to severe muscle weakness. In Europe and the USA, around 1 to 2 cases per 100,000 people occur annually.

GBS usually begins with weakness and tingling in the legs that can spread to the upper body and arms. Walking and moving becomes increasingly difficult. In severe cases, paralysis of the respiratory muscles can also occur. Although GBS is considered an autoimmune disease, the underlying mechanisms are still largely unknown. This makes accurate diagnosis and effective treatment difficult.

One recently published in the journal Nature external sitestudycall_made led by Daniela Latorre, SNSF group leader at the Institute of Microbiology at ETH Zurich, now uncovers a central aspect  of the pathophysiology of GBS . In close collaboration with clinical researchers at the University Hospital of Zurich and the Neurocenter of Southern Switzerland (EOC) in Lugano, Latorre searched for autoimmune factors that are responsible for this disease.

Autoreactive T cells attack peripheral nerves

Using highly sensitive measurement methods, Latorre’s group was able to demonstrate that in GBS patients, specific cells of the immune system, so-called T lymphocytes, penetrate the nerve tissue and react to the insulating covering of the nerve fibers, the myelin sheath.

In healthy people, T lymphocytes play a key role in the immune defense by recognizing and eliminating foreign structures, for example in viral infections, and abnormal endogenous cells. However, in rare cases, T cells can mistakenly attack the body’s own tissue, leading to autoimmune diseases.

“We found that these autoreactive T lymphocytes only occur in patients with a GBS variant in which the myelin layer of the nerves is damaged,” explains Latorre. And that the T cells have a disease-specific signature that distinguishes them from healthy people. The results provide evidence for the first time that autoreactive T lymphocytes contribute significantly to this clinical picture in humans.

In addition, in a subgroup of GBS patients following a viral infection, the researchers identified T lymphocytes that responded to both the self-antigens of the myelin sheath and the viral antigens. This suggests a direct connection between GBS disease and the previous viral infection .

Although current therapies are effective for many GBS patients, they are not specific enough, so around twenty percent of patients remain severely disabled or die. The researchers’ findings contribute to a better understanding of this disease and pave the way for follow-up studies with larger patient groups in order to decipher additional GBS variants. This could one day lead to targeted therapies for GBS subtypes and thus significantly improve patient care.

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