Peptides From the Variable Domain of Immunoglobulin G as Biomarkers in Chronic Inflammatory Demyelinating Polyradiculoneuropathy.
Journal
Neurology(R) neuroimmunology & neuroinflammation
ISSN: 2332-7812
Titre abrégé: Neurol Neuroimmunol Neuroinflamm
Pays: United States
ID NLM: 101636388
Informations de publication
Date de publication:
11 2023
11 2023
Historique:
received:
27
03
2023
accepted:
24
07
2023
medline:
31
8
2023
pubmed:
29
8
2023
entrez:
28
8
2023
Statut:
epublish
Résumé
Chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) is a clinically heterogeneous immune-mediated disease. Diagnostic biomarkers for CIDP are currently lacking. Peptides derived from the variable domain of circulating immunoglobulin G (IgG) have earlier been shown to be shared among patients with the same immunologic disease. Because humoral immune factors are hypothesized to be involved in the pathogenesis of CIDP, we evaluated IgG variable domain-derived peptides as diagnostic biomarkers in CIDP (primary objective) and whether IgG-derived peptides could cluster objective clinical entities in CIDP (secondary objective). IgG-derived peptides were determined in prospectively collected sera of patients with CIDP and neurologic controls by means of mass spectrometry. Peptides of interest were selected through statistical analysis in a discovery cohort followed by sequence determination and confirmation. Diagnostic performance was evaluated for individual selected peptides and for a multipeptide model incorporating selected peptides, followed by performance reassessment in a validation cohort. Clustering of patients with CIDP based on IgG-derived peptides was evaluated through unsupervised sparse principal component analysis followed by k-means clustering. Sixteen peptides originating from the IgG variable domain were selected as candidate biomarkers in a discovery cohort of 44 patients with CIDP and 29 neurologic controls. For all 16 peptides, univariate logistic regressions and ROC curve analysis demonstrated increasing peptide abundances to associate with increased odds for CIDP (area under the curves [AUCs] ranging from 64.6% to 79.6%). When including age and sex in the logistic regression models, this remained the case for 13/16 peptides. A model composed of 5/16 selected peptides showed strong discriminating performance between patients with CIDP and controls (AUC 91.5%; 95% CI 84.6%-98.4%; IgG variable domain-derived peptides showed a valid source for diagnostic biomarkers in CIDP, albeit with challenges toward replication. Our proof-of-concept findings warrant further study of IgG-derived peptides as biomarkers in more homogeneous cohorts of patients with CIDP and controls. This study provides Class III evidence that the pattern of serum IgG-derived peptide clusters may help differentiate between patients with CIDP and those with other peripheral neuropathies.
Sections du résumé
BACKGROUND AND OBJECTIVES
Chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) is a clinically heterogeneous immune-mediated disease. Diagnostic biomarkers for CIDP are currently lacking. Peptides derived from the variable domain of circulating immunoglobulin G (IgG) have earlier been shown to be shared among patients with the same immunologic disease. Because humoral immune factors are hypothesized to be involved in the pathogenesis of CIDP, we evaluated IgG variable domain-derived peptides as diagnostic biomarkers in CIDP (primary objective) and whether IgG-derived peptides could cluster objective clinical entities in CIDP (secondary objective).
METHODS
IgG-derived peptides were determined in prospectively collected sera of patients with CIDP and neurologic controls by means of mass spectrometry. Peptides of interest were selected through statistical analysis in a discovery cohort followed by sequence determination and confirmation. Diagnostic performance was evaluated for individual selected peptides and for a multipeptide model incorporating selected peptides, followed by performance reassessment in a validation cohort. Clustering of patients with CIDP based on IgG-derived peptides was evaluated through unsupervised sparse principal component analysis followed by k-means clustering.
RESULTS
Sixteen peptides originating from the IgG variable domain were selected as candidate biomarkers in a discovery cohort of 44 patients with CIDP and 29 neurologic controls. For all 16 peptides, univariate logistic regressions and ROC curve analysis demonstrated increasing peptide abundances to associate with increased odds for CIDP (area under the curves [AUCs] ranging from 64.6% to 79.6%). When including age and sex in the logistic regression models, this remained the case for 13/16 peptides. A model composed of 5/16 selected peptides showed strong discriminating performance between patients with CIDP and controls (AUC 91.5%; 95% CI 84.6%-98.4%;
DISCUSSION
IgG variable domain-derived peptides showed a valid source for diagnostic biomarkers in CIDP, albeit with challenges toward replication. Our proof-of-concept findings warrant further study of IgG-derived peptides as biomarkers in more homogeneous cohorts of patients with CIDP and controls.
CLASSIFICATION OF EVIDENCE
This study provides Class III evidence that the pattern of serum IgG-derived peptide clusters may help differentiate between patients with CIDP and those with other peripheral neuropathies.
Identifiants
pubmed: 37640545
pii: 10/6/e200162
doi: 10.1212/NXI.0000000000200162
pmc: PMC10462053
pii:
doi:
Substances chimiques
Immunoglobulin G
0
Biomarkers
0
Peptides
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Informations de copyright
Copyright © 2023 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the American Academy of Neurology.
Références
Nature. 2022 Sep;609(7929):998-1004
pubmed: 36131022
J Peripher Nerv Syst. 2011 Jun;16 Suppl 1:3-13
pubmed: 21696490
Arch Neurol. 1980 Oct;37(10):637-40
pubmed: 6252877
J Neuroimmunol. 2000 May 1;104(2):139-46
pubmed: 10713353
J Neurol Neurosurg Psychiatry. 2015 Sep;86(9):973-85
pubmed: 25677463
Front Immunol. 2018 Feb 01;9:117
pubmed: 29449843
Hum Mol Genet. 2017 Nov 15;26(22):4451-4464
pubmed: 29036575
Neurology. 2015 Aug 11;85(6):498-504
pubmed: 26180143
N Biotechnol. 2021 Jan 25;60:168-172
pubmed: 33045420
J Allergy Clin Immunol. 2010 Feb;125(2 Suppl 2):S41-52
pubmed: 20176268
Neurol Neuroimmunol Neuroinflamm. 2021 Nov 29;9(1):
pubmed: 34845096
Curr Opin Neurol. 2019 Oct;32(5):651-657
pubmed: 31306213
JAMA Neurol. 2020 Sep 1;77(9):1159-1166
pubmed: 32338716
Brain. 2003 Feb;126(Pt 2):361-75
pubmed: 12538403
Transfus Apher Sci. 2017 Feb;56(1):45-49
pubmed: 28161150
Nucleic Acids Res. 2013 Jul;41(Web Server issue):W34-40
pubmed: 23671333
J Neurol Sci. 2018 Jan 15;384:107-112
pubmed: 29249367
Neurol Clin Pract. 2013 Oct;3(5):440-445
pubmed: 29473612
Nucleic Acids Res. 2009 Jan;37(Database issue):D1006-12
pubmed: 18978023
Mol Cell Proteomics. 2013 Dec;12(12):3924-34
pubmed: 23970564
J Neurol Sci. 1992 Jan;107(1):111-21
pubmed: 1578228
J Autoimmun. 2012 Jun;38(4):354-60
pubmed: 22459491
PLoS One. 2014 May 01;9(5):e96029
pubmed: 24787687
Sci Rep. 2017 Oct 31;7(1):14411
pubmed: 29089585
JAMA. 2004 May 19;291(19):2367-75
pubmed: 15150209
J Neurol Neurosurg Psychiatry. 2019 Jun;90(6):674-680
pubmed: 30904899
Neurol Neuroimmunol Neuroinflamm. 2021 Jan 6;8(2):
pubmed: 33408168
Front Immunol. 2022 Dec 09;13:1038411
pubmed: 36569912
Neurology. 1980 Aug;30(8):864-7
pubmed: 6251407
Neuroepidemiology. 2019;52(3-4):161-172
pubmed: 30669140
J Neurol Neurosurg Psychiatry. 2019 Sep;90(9):988-996
pubmed: 31227562
Eur J Neurol. 2010 Mar;17(3):356-63
pubmed: 20456730