Classifying dementias from the IgM IgOme

Spectral analysis of the reactivity graph as a biomarker-mining strategy that exploits the previously neglected IgM repertoire..

Project · Case study

Spectral analysis of the reactivity graph as a biomarker-mining strategy that exploits the previously neglected IgM repertoire.

Problem

Different neurodegenerative diseases are hard to distinguish from serum. Does the IgM antibody reactivity landscape carry a discriminative signal?

Method

Spectral embedding of the reactivity graph onto a low-dimensional manifold, followed by UMAP for further dimensionality reduction to visualize and compare IgM- and IgG-derived representations¹.

Result & open questions

The IgM IgOme identifies a common change in the IgM repertoire across neurodegenerative diseases – a large proportion of the normally present (natural?) IgM specificities is lost. Open: Does the fact that IgG reactivity on a standard public IgM mimotope library distinguishes diseases better than primary IgM reactivity indicate autoimmunity?

Related: Reading a reactivity graph

References

1.

Pashova-Dimova, S. et al. Changes in the public IgM repertoire and its idiotypic connectivity in alzheimer’s disease and frontotemporal dementia. J Neuroimmunol 409, 578775 (2025).