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CIDP Antibodies Target Junction Proteins and Identify Patient Subgroups: An Autoantigenomic Approach.

Christian P Moritz¹, Yannick Tholance², Oda Stoevesandt²

¹From the Department of Neurology (C.P.M., K.F., J.-P.C., J.-C.A.), and Department of Biochemistry (Y.T.), University Hospital of Saint-Etienne; Synaptopathies and Autoantibodies (C.P.M., Y.T., J.-P.C., J.-C.A.), Institut NeuroMyoGène, INSERM U1217/CNRS UMR 5310, University of Lyon, University Jean-Monnet, Saint-Étienne, France; and Cambridge Protein Arrays Ltd. (O.S.), Babraham Research Campus, United Kingdom. christian.moritz@univ-st-etienne.fr.

Neurology(R) Neuroimmunology & Neuroinflammation

|January 7, 2021

Summary

Researchers identified distinct autoantigen repertoires in chronic inflammatory demyelinating polyneuropathy (CIDP) patients, revealing potential diagnostic markers and therapeutic targets. Autoantigenomic analysis offers insights into CIDP pathogenesis and patient stratification.

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Area of Science:

Neuroimmunology
Proteomics
Bioinformatics

Background:

Chronic inflammatory demyelinating polyneuropathy (CIDP) is a rare autoimmune disorder affecting peripheral nerves.
Understanding the autoantigen repertoire in CIDP is crucial for diagnosis and treatment.

Purpose of the Study:

To systematically analyze the autoantigen repertoires in patients with CIDP compared to controls.
To identify systemic characteristics and potential novel autoantigens associated with CIDP.

Main Methods:

Screening of 43 human serum samples (22 CIDP, 12 other neuropathies, 9 controls) using HuProt Human Proteome microarrays (~16,000 proteins).
Bioinformatical autoantigenomic approaches including principal component analysis, repertoire size analysis, and overrepresentation analyses (Gene Ontology, PantherDB).

Main Results:

CIDP autoantigen repertoires differed systematically from controls.
A subgroup of CIDP patients (younger onset, mixed motor/sensory) showed distinct repertoires.
Anchoring junction components were targeted by 86.4% of CIDP patients; novel potential autoantigens identified (e.g., actin-related protein 2/3 complex subunit 1B, ezrin).

Conclusions:

Systematic autoantigenomic analysis provides insights into CIDP.
Identified autoantigens may improve diagnosis, treatment, and patient stratification for CIDP.