IMAGiNE Study Publications

The Role of Complement Activation in IgM M-Protein–Associated Neuropathies

2025

Aim of the study

Anti-MAG antibodies are thought to contribute to nerve damage by triggering another part of the immune system called complement, which can cause inflammation and injury.

In this study, researchers analyzed blood samples from 101 patients to better understand how these antibodies and complement activation are related to each other and to disease severity. They used lab tests to measure how strongly the antibodies reacted to MAG and whether this reaction led to activation of the complement system.

What did the researchers find?

• People had very different levels of anti-MAG antibodies, from none at all to very high.
• In general, higher levels of anti-MAG antibodies led to more complement activation in the lab.
• However, some patients without anti-MAG antibodies also showed signs of complement activation, suggesting that other harmful antibodies may be involved.
• Importantly, the amount of nerve damage or symptoms a patient had did not clearly match with antibody levels or complement activation.

What does this mean for patients?

While the study confirms that anti-MAG antibodies can trigger immune responses, it also shows that these responses do not always explain how severe someone’s symptoms are. More research is needed to understand which patients might benefit from which treatments.

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IgM anti-MAG^± peripheral neuropathy (IMAGiNe) study protocol: An international, observational, prospective registry of patients with IgM M-protein peripheral neuropathies

2023

This article outlines how previous clinical trials in this area have often failed to provide meaningful results, largely due to small sample sizes, short follow-up times, inconsistent use of outcome measures, and a lack of standardization in data collection. As a result, there is still no strong evidence base for how best to monitor or treat these patients.

To address these challenges, the article describes in detail the setup of the IMAGiNe study. Standardized clinical assessments at each timepoint are:

• Documentation of symptoms, disease course, treatments, and response to therapy
• Laboratory and electrophysiological data, including antibody titers
• Development of a new disease-specific patient-reported outcome measure (IgM-PNP-RODS)
• Optional biobanking of blood and DNA samples

Ultimately, this article lays the foundation for future research into IgM PNP by establishing a structured, standardized, and international framework for studying the natural history of the disease, identifying subtypes, and developing validated outcome measures. At the time of publication, 236 patients from multiple countries had already been enrolled, with more centers in the process of joining.

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