CIDP Antibodies Target Junction Proteins and Identify Patient Subgroups

Abstract

ObjectiveTo discover systemic characteristics in the repertoires of targeted autoantigens in chronic inflammatory demyelinating polyneuropathy (CIDP), we detected the entire autoantigen repertoire of patients and controls and analyzed them systematically.MethodsWe screened 43 human serum samples, of which 22 were from patients with CIDP, 12 from patients with other neuropathies, and 9 from healthy controls via HuProt Human Proteome microarrays testing about 16,000 distinct human bait proteins. Autoantigen repertoires were analyzed via bioinformatical autoantigenomic approaches: principal component analysis, analysis of the repertoire sizes in disease groups and clinical subgroups, and overrepresentation analyses using Gene Ontology and PantherDB.ResultsThe autoantigen repertoires enabled the identification of a subgroup of 10/22 patients with CIDP with a younger age at onset and a higher frequency of mixed motor and sensory CIDP. IV immunoglobulin therapy responders targeted 3 times more autoantigens than nonresponders. No CIDP-specific autoantibody is present in all patients; however, anchoring junction components were significantly targeted by 86.4% of patients with CIDP. There are potential novel CIDP-specific autoantigens such as the myelination- or axo-glial structure–related proteins actin-related protein 2/3 complex subunit 1B, band 4.1-like protein 2, cadherin-15, cytohesin-1, epidermal growth factor receptor, ezrin, and radixin.ConclusionsThe repertoire of targeted autoantigens of patients with CIDP differs in a systematic degree from those of controls. Systematic autoantigenomic approaches can help to understand the disease and to discover novel bioinformatical tools and novel autoantigen panels to improve diagnosis, treatment, prognosis, or patient stratification.

Guillain-Barré Syndrome Following Zika Virus Infection Is Associated With a Diverse Spectrum of Peripheral Nerve Reactive Antibodies

“…An alternative approach is offered by highthroughput antibody screening techniques such as the newly described Rapid Extracellular Antigen Profiling technique, 38,39 or chip-based proteome profiling, 40 which has recently offered insights into the autoantibody repertoire of patients with chronic inflammatory demyelinating polyradiculoneuropathy. 41 Our findings mirror our recent screening of a separate cohort of 100 patients with GBS, where we report a similarly heterogeneous reactivity of their IgG and IgM antibodies to nerve-related antigens. 20 The narrow definition of the present GBS cohort, in which all patients associated with the same infectious insult, suggests that the heterogeneity of the humoral immune responses in GBS may be a core feature of the disease and not necessarily due to the heterogeneity of the patient cohorts or prodromal infections.…”

“…An alternative approach is offered by high-throughput antibody screening techniques such as the newly described Rapid Extracellular Antigen Profiling technique, 38 , 39 or chip-based proteome profiling, 40 which has recently offered insights into the autoantibody repertoire of patients with chronic inflammatory demyelinating polyradiculoneuropathy. 41 …”

Guillain-Barré syndrome following Zika virus infection is associated with a diverse spectrum of peripheral nerve reactive antibodies

“…An alternative approach is offered by high throughput antibody screening techniques such as the newly described Rapid Extracellular Antigen Profiling (REAP) technique, [31,32] or chip-based proteome profiling [33], which has recently offered insights into the autoantibody repertoire of patients with chronic inflammatory demyelinating polyradiculoneuropathy (CIDP). [34] Our findings mirror our recent screening of a separate cohort of 100 GBS patients, where we report a similarly heterogeneous reactivity of IgG and IgM to nerve-related antigens. [35] The narrow definition of the present GBS cohort, in which all patients associated with the same infectious insult, suggest that heterogeneity of the humoral immune responses in GBS may be a core feature of the disease and not necessarily due to heterogeneity of the patient cohorts.…”

A Mendelian randomization study identifies proteins involved in neurodegenerative diseases

“…126 A member of the cadherin protein family, CDH15, participates in the function of the node of Ranvier and has previously been associated with chronic inflammatory demyelinating polyneuropathy, a demyelinating disease of the peripheral nervous system. 127 Lesions in the dorsal root ganglion are identified in EAE, 128,129 and FLRT3, a newly-identified protein related to MS, is overexpressed in the dorsal root ganglion and has been associated with neuropathic pain in animal models. 130 Four further newly-identified MS-associated loci (PVALB, TST, ASF1A) potentially indicate additional molecular pathways contributing to MS. PVALB is specifically expressed by GABAergic interneurons and has been suggested as a potential MS-specific marker of grey matter neuro-degeneration.…”