Immunoprofiling of active and inactive systemic juvenile idiopathic arthritis reveals distinct biomarkers: a single-center study.
Cytokines and inflammatory mediators
High mobility group Box 1
Inflammation
Ingenuity pathway analysis
Proteomics
Systemic juvenile idiopathic arthritis
Journal
Pediatric rheumatology online journal
ISSN: 1546-0096
Titre abrégé: Pediatr Rheumatol Online J
Pays: England
ID NLM: 101248897
Informations de publication
Date de publication:
28 Dec 2021
28 Dec 2021
Historique:
received:
06
10
2021
accepted:
15
12
2021
entrez:
29
12
2021
pubmed:
30
12
2021
medline:
4
2
2022
Statut:
epublish
Résumé
This study aimed to perform an immunoprofiling of systemic juvenile idiopathic arthritis (sJIA) in order to define biomarkers of clinical use as well as reveal new immune mechanisms. Immunoprofiling of plasma samples from a clinically well-described cohort consisting of 21 sJIA patients as well as 60 age and sex matched healthy controls, was performed by a highly sensitive proteomic immunoassay. Based on the biomarkers being significantly up- or down-regulated in cross-sectional and paired analysis, related canonical pathways and cellular functions were explored by Ingenuity Pathway Analysis (IPA). The well-studied sJIA biomarkers, IL6, IL18 and S100A12, were confirmed to be increased during active sJIA as compared to healthy controls. IL18 was the only factor found to be increased during inactive sJIA as compared to healthy controls. Novel factors, including CASP8, CCL23, CD6, CXCL1, CXCL11, CXCL5, EIF4EBP1, KITLG, MMP1, OSM, SIRT2, SULT1A1 and TNFSF11, were found to be differentially expressed in active and/or inactive sJIA and healthy controls. No significant pathway activation could be predicted based on the limited factor input to the IPA. High Mobility Group Box 1 (HMGB1), a damage associated molecular pattern being involved in a series of inflammatory diseases, was determined to be higher in active sJIA than inactive sJIA. We could identify a novel set of biomarkers distinguishing active sJIA from inactive sJIA or healthy controls. Our findings enable a better understanding of the immune mechanisms active in sJIA and aid the development of future diagnostic and therapeutic strategies.
Sections du résumé
BACKGROUND
BACKGROUND
This study aimed to perform an immunoprofiling of systemic juvenile idiopathic arthritis (sJIA) in order to define biomarkers of clinical use as well as reveal new immune mechanisms.
METHODS
METHODS
Immunoprofiling of plasma samples from a clinically well-described cohort consisting of 21 sJIA patients as well as 60 age and sex matched healthy controls, was performed by a highly sensitive proteomic immunoassay. Based on the biomarkers being significantly up- or down-regulated in cross-sectional and paired analysis, related canonical pathways and cellular functions were explored by Ingenuity Pathway Analysis (IPA).
RESULTS
RESULTS
The well-studied sJIA biomarkers, IL6, IL18 and S100A12, were confirmed to be increased during active sJIA as compared to healthy controls. IL18 was the only factor found to be increased during inactive sJIA as compared to healthy controls. Novel factors, including CASP8, CCL23, CD6, CXCL1, CXCL11, CXCL5, EIF4EBP1, KITLG, MMP1, OSM, SIRT2, SULT1A1 and TNFSF11, were found to be differentially expressed in active and/or inactive sJIA and healthy controls. No significant pathway activation could be predicted based on the limited factor input to the IPA. High Mobility Group Box 1 (HMGB1), a damage associated molecular pattern being involved in a series of inflammatory diseases, was determined to be higher in active sJIA than inactive sJIA.
CONCLUSIONS
CONCLUSIONS
We could identify a novel set of biomarkers distinguishing active sJIA from inactive sJIA or healthy controls. Our findings enable a better understanding of the immune mechanisms active in sJIA and aid the development of future diagnostic and therapeutic strategies.
Identifiants
pubmed: 34963488
doi: 10.1186/s12969-021-00660-9
pii: 10.1186/s12969-021-00660-9
pmc: PMC8713412
doi:
Substances chimiques
Biomarkers
0
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
173Subventions
Organisme : Karolinska Institutet
ID : KIK2HEH
Organisme : Vetenskapsrådet
ID : 2018-02885
Organisme : region Stockholm
ID : 20190592
Organisme : China Scholarship Council
ID : 201807930002
Informations de copyright
© 2021. The Author(s).
Références
Mediators Inflamm. 2013;2013:434010
pubmed: 23533306
J Cell Sci. 2010 Dec 15;123(Pt 24):4251-8
pubmed: 21081649
Clin Immunol. 2015 Jul;159(1):72-83
pubmed: 25956529
Arthritis Rheum. 2007 Mar;56(3):965-71
pubmed: 17328073
Nucleic Acids Res. 2015 Jul 1;43(W1):W566-70
pubmed: 25969447
Pediatr Clin North Am. 2018 Aug;65(4):691-709
pubmed: 30031494
J Rheumatol. 2014 Jun;41(6):1171-7
pubmed: 24786929
Apoptosis. 2004 Nov;9(6):677-90
pubmed: 15505411
Arthritis Rheumatol. 2020 Sep;72(9):1505-1513
pubmed: 32307907
Ann Rheum Dis. 2019 Aug;78(8):1107-1113
pubmed: 31005900
ISRN Inflamm. 2013 Dec 08;2013:512103
pubmed: 24381786
Ann Rheum Dis. 2007 May;66(5):589-98
pubmed: 17170049
J Rheumatol. 2004 Feb;31(2):390-2
pubmed: 14760812
Lupus. 2014 Mar;23(3):305-12
pubmed: 24399813
Arthritis Care Res (Hoboken). 2011 Jul;63(7):929-36
pubmed: 21717596
J Exp Med. 2016 Jul 25;213(8):1387-97
pubmed: 27377588
Pediatr Rheumatol Online J. 2021 Jul 12;19(1):112
pubmed: 34247641
J Clin Invest. 1994 May;93(5):2114-9
pubmed: 8182142
Mol Med. 2021 May 11;27(1):48
pubmed: 33975537
J Rheumatol. 2013 Sep;40(9):1604-13
pubmed: 23858044
Rheumatology (Oxford). 2021 May 14;60(5):2421-2426
pubmed: 33200207
Ann Rheum Dis. 2017 Jan;76(1):166-172
pubmed: 27296321
J Rheumatol. 2004 May;31(5):986-91
pubmed: 15124262
Cell. 2020 Nov 12;183(4):968-981.e7
pubmed: 32966765
Ann Rheum Dis. 2011 May;70(5):747-54
pubmed: 21173013
Eur Cytokine Netw. 2009 Jun;20(2):75-80
pubmed: 19541593
Arthritis Rheumatol. 2020 Feb;72(2):210-219
pubmed: 31524322
Arthritis Res Ther. 2011 May 06;13(3):R71
pubmed: 21548924
Clin Immunol. 2015 Oct;160(2):277-81
pubmed: 26101092
Clin Exp Immunol. 2005 Dec;142(3):446-53
pubmed: 16297156
N Engl J Med. 2012 Dec 20;367(25):2385-95
pubmed: 23252525
Arthritis Res Ther. 2015 Aug 07;17:200
pubmed: 26249667
Clin Rheumatol. 2008 Mar;27(3):289-94
pubmed: 17703334
Rheumatology (Oxford). 2020 Sep 1;59(9):2392-2401
pubmed: 31904851
Biochem Biophys Res Commun. 2013 Nov 29;441(4):897-903
pubmed: 24211200
Arthritis Res Ther. 2008;10(2):R33
pubmed: 18346273
Arthritis Res. 2002;4(3):157-64
pubmed: 12010565
Inflamm Bowel Dis. 2020 May 12;26(6):874-884
pubmed: 31901089
Best Pract Res Clin Rheumatol. 2017 Aug;31(4):505-516
pubmed: 29773270