HOLISTIC CHARACTERIZATION OF THE AUTOANTIGEN REPERTOIRE IN CHRONIC INFLAMMATORY DEMYELINATING POLYNEUROPATHY VIA AUTOANTIGENOMICS
- Christian P. Moritz, France
Abstract
Background and Aims
To characterize the repertoires of targeted autoantigens in chronic inflammatory demyelinating polyneuropathy (CIDP) for systemic peculiarities, we detected the autoantigens of patients and controls and analyzed them in a holistic way.
Methods
We screened 43 human sera, comprising 22 CIDP patients, 12 patients with other neuropathies (ONP), and 9 apparently healthy controls (HC) via HuProt protein microarrays testing about 16,000 distinct human bait proteins in parallel. Autoantigen repertoires were analyzed via bioinformatical approaches of autoantigenomics: principle component and hierarchical cluster analysis, analysis of the repertoire sizes in disease groups and clinical subgroups, overrepresentation analyses using databases like those of Gene Ontology, Reactome Pathway, and pathway representation.
Results
1) The cohort of CIDP patients was heterogeneous regarding their autoantigen repertoires; 2) the number of the targeted antigens per CIDP patient depended on the clinical situation: intravenous immunoglobulin therapy responders targeted three times more autoantigens than non-responders; 3) a significant part of the autoantibody set specifically targeted proteins involved in anchoring junction components, motile cilium proteins, glycoprotein metabolic processes, and certain signaling pathway proteins; 4) ≥9 out of 23 central signaling proteins of the growth factor receptor pathway are targeted by CIDP-specific antibodies.
Conclusions
The repertoire of targeted autoantigens of CIDP patients differs systematically from those of controls. Considering systemic autoantigenomic approaches in addition to single antibody approaches may help to understand the disease and to discover novel options for improved diagnosis and prognosis.