A review article published in Nature Reviews Neurology, whose first author is Dr. Marta Caballero from the team of Dr. Luis Querol, member of the Neuromuscular Diseases Group at the Sant Pau Research Institute (IR Sant Pau), analyzes recent advances in the diagnosis and treatment of primary autoimmune neuropathies—a group of rare and debilitating disorders of the peripheral nervous system that includes Guillain–Barré syndrome (GBS) and chronic inflammatory demyelinating polyradiculoneuropathy (CIDP).
For more than three decades, the therapeutic approach to these disorders has relied on nonspecific strategies such as intravenous immunoglobulin, corticosteroids, or plasma exchange. Although these have improved the prognosis for many patients, their effectiveness is limited, and not everyone responds in the same way. Moreover, these therapies do not target the specific mechanisms that trigger the disease.
The review article explains how, lately, research has enabled a qualitative leap in this field. One of the most significant advances is the identification of autoantibodies directed against essential proteins at the nodes of Ranvier—structures critical for the transmission of nerve impulses. This finding, in which the Neuromuscular Diseases Unit at Sant Pau Hospital has played a leading role, led to the recognition of a new diagnostic category: autoimmune nodopathies. These are neuropathies in which the immune system specifically attacks these regions of the nerve fiber, disrupting communication between neurons and causing weakness and loss of sensation.
This new concept helps explain the clinical heterogeneity of some patients and opens the door to more targeted treatments. At the same time, the diagnostic criteria for GBS and CIDP have been redefined, enabling more accurate detection of disease, reducing misclassification, and better guiding therapeutic decisions.
The article coordinated by Dr. Querol also reviews targeted therapies that are beginning to reach clinical practice. A notable example is efgartigimod, recently approved in Europe and the United States as the first specific treatment for CIDP. This drug lowers the levels of pathogenic antibodies in the blood and represents a paradigm shift after more than 30 years without therapeutic innovations of this magnitude. In addition, clinical trials are underway with complement inhibitors, which have shown promising results not only in CIDP but also in GBS and multifocal motor neuropathy.
Another key aspect is biomarkers, which provide objective information about disease activity and progression. Among the most promising are serum neurofilament light chain, which reflects axonal damage, as well as specific autoantibodies and proteins unique to peripheral nerves, such as peripherin or periaxin. Validating these biomarkers will not only allow earlier diagnosis but also help predict treatment response and personalize patient follow-up.
“The field of autoimmune neuropathies is undergoing a true transformation,” explains Dr. Marta Caballero. “We are moving from general therapies to strategies that target the exact mechanisms causing the disease. This means we will be able to be much more precise, reduce treatment toxicity, and improve patients’ quality of life.”
Dr. Querol, for his part, emphasizes the importance of the new biomarkers. “Thanks to these tools, we will not only be able to diagnose more quickly and reliably, but also to monitor disease progression and treatment response in an objective way. This is an essential step toward advancing personalized medicine in this field.”
The advances summarized in this review place primary autoimmune neuropathies—until now considered orphan diseases in terms of innovation—at the center of a paradigm shift. More profound understanding of their mechanisms, the availability of more rigorous diagnostic criteria, the arrival of new targeted therapies. The development of reliable biomarkers will allow patients to receive care that is more effective, safer, and tailored to their individual needs.
Reference Article:
Caballero-Ávila M, Pascual-Goñi E, Lleixà C, Martín-Aguilar L, Collet-Vidiella R, Querol L. The changing landscape of primary autoimmune neuropathies. Nat Rev Neurol 2025. https://doi.org/10.1038/s41582-025-01133-3
