PTPN22 1858C>T polymorphism is associated with increased CD154 expression and higher CD4+ T cells percentage in rheumatoid arthritis patients.
Adult
Aged
Arthritis, Rheumatoid
/ epidemiology
CD4-Positive T-Lymphocytes
/ immunology
CD40 Ligand
/ analysis
Cohort Studies
Female
Genetic Predisposition to Disease
/ epidemiology
Humans
Interferon-gamma
/ blood
Lymphocyte Count
Male
Middle Aged
Polymorphism, Single Nucleotide
/ genetics
Protein Tyrosine Phosphatase, Non-Receptor Type 22
/ genetics
CD154
CD40
IFN-γ
PTPN22
anti-CCP positive
rheumatoid arthritis
Journal
Journal of clinical laboratory analysis
ISSN: 1098-2825
Titre abrégé: J Clin Lab Anal
Pays: United States
ID NLM: 8801384
Informations de publication
Date de publication:
Mar 2019
Mar 2019
Historique:
received:
14
09
2018
revised:
13
10
2018
accepted:
14
10
2018
pubmed:
8
11
2018
medline:
30
4
2019
entrez:
8
11
2018
Statut:
ppublish
Résumé
CD40 is a costimulatory molecule for B cells, and CD154 is a marker of CD4+ T cells activation. CD40-CD154 interaction promotes pro-inflammatory cytokines secretion and autoantibodies production. PTPN22 gene encodes LYP protein, an inhibitor of T- and B-cell activation. PTPN22 1858C>T polymorphism confers rheumatoid arthritis (RA) susceptibility. Hence, we evaluate the relationship between 1858C>T polymorphism with CD40 and CD154 expression and IFN-γ secretion in RA patients. PTPN22 1858C>T polymorphism was genotyped in 315 RA patients and 315 control subjects (CS) using PCR-RFLP method. Later, we selected only ten anti-CCP-positive RA patients, naïve to disease-modifying antirheumatic drugs and ten CS, all with known 1858C>T PTPN22 genotype. The CD40 and CD154 membrane expressions were determined by flow cytometry in peripheral B and T cells, correspondingly. The B cells percentage and mCD40 expression were similar between RA and CS (P > 0.05) and we did not find an association between these variables and the 1858C>T polymorphism. The CD4+ T cells percentage was higher in RA patients than CS (P = 0.003), and in the RA group, the CD4+ T cells percentage and mCD154 expression were higher in the 1858 T allele carriers (P = 0.008 and P = 0.032, respectively). The IFN-γ levels were lower in RA patients carrying the PTPN22 risk allele (P = 0.032). The PTPN22 1858 T risk allele is associated with increased CD4+ T cells percentage and high mCD154 expression in RA patients, which could favor the pro-inflammatory cytokine release and the establishment of the inflammatory response at the seropositive RA.
Sections du résumé
BACKGROUND
BACKGROUND
CD40 is a costimulatory molecule for B cells, and CD154 is a marker of CD4+ T cells activation. CD40-CD154 interaction promotes pro-inflammatory cytokines secretion and autoantibodies production. PTPN22 gene encodes LYP protein, an inhibitor of T- and B-cell activation. PTPN22 1858C>T polymorphism confers rheumatoid arthritis (RA) susceptibility. Hence, we evaluate the relationship between 1858C>T polymorphism with CD40 and CD154 expression and IFN-γ secretion in RA patients.
METHODS
METHODS
PTPN22 1858C>T polymorphism was genotyped in 315 RA patients and 315 control subjects (CS) using PCR-RFLP method. Later, we selected only ten anti-CCP-positive RA patients, naïve to disease-modifying antirheumatic drugs and ten CS, all with known 1858C>T PTPN22 genotype. The CD40 and CD154 membrane expressions were determined by flow cytometry in peripheral B and T cells, correspondingly.
RESULTS
RESULTS
The B cells percentage and mCD40 expression were similar between RA and CS (P > 0.05) and we did not find an association between these variables and the 1858C>T polymorphism. The CD4+ T cells percentage was higher in RA patients than CS (P = 0.003), and in the RA group, the CD4+ T cells percentage and mCD154 expression were higher in the 1858 T allele carriers (P = 0.008 and P = 0.032, respectively). The IFN-γ levels were lower in RA patients carrying the PTPN22 risk allele (P = 0.032).
CONCLUSION
CONCLUSIONS
The PTPN22 1858 T risk allele is associated with increased CD4+ T cells percentage and high mCD154 expression in RA patients, which could favor the pro-inflammatory cytokine release and the establishment of the inflammatory response at the seropositive RA.
Identifiants
pubmed: 30402903
doi: 10.1002/jcla.22710
pmc: PMC6818609
doi:
Substances chimiques
CD40 Ligand
147205-72-9
Interferon-gamma
82115-62-6
PTPN22 protein, human
EC 3.1.3.48
Protein Tyrosine Phosphatase, Non-Receptor Type 22
EC 3.1.3.48
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
e22710Subventions
Organisme : Consejo Nacional de Ciencia y Tecnología: SSA-IMSS-ISSSTE-CONACYT
ID : registration#161749
Informations de copyright
© 2018 Wiley Periodicals, Inc.
Références
J Immunol. 2009 Mar 15;182(6):3343-7
pubmed: 19265110
Int J Genomics. 2017;2017:8753498
pubmed: 28210620
J Clin Lab Anal. 2019 Mar;33(3):e22710
pubmed: 30402903
Mol Med. 2011 Sep-Oct;17(9-10):901-9
pubmed: 21607290
Pediatr Diabetes. 2013 Jun;14(4):304-10
pubmed: 22809281
Sci Rep. 2017 Apr 24;7:46652
pubmed: 28436448
J Clin Invest. 1997 Nov 1;100(9):2404-14
pubmed: 9410920
Nat Immunol. 2010 Jun;11(6):464-6
pubmed: 20485272
Biochem Biophys Res Commun. 2014 Sep 19;452(2):254-62
pubmed: 25078624
Am J Hum Genet. 2004 Aug;75(2):330-7
pubmed: 15208781
J Immunol. 2009 Apr 1;182(7):4093-106
pubmed: 19299707
Hum Immunol. 2013 May;74(5):574-85
pubmed: 23333624
Nat Genet. 2011 Aug 14;43(9):902-7
pubmed: 21841778
Calcif Tissue Int. 2018 May;102(5):533-546
pubmed: 29204672
Ann Rheum Dis. 2000 Mar;59(3):190-5
pubmed: 10700427
Nat Immunol. 2012 Apr 18;13(5):439-47
pubmed: 22513334
Xi Bao Yu Fen Zi Mian Yi Xue Za Zhi. 2013 Aug;29(8):854-7
pubmed: 23948414
Rheumatology (Oxford). 2006 Aug;45(8):1009-11
pubmed: 16490755
Ann Rheum Dis. 2013 Aug;72(8):1420-4
pubmed: 23661491
Zhonghua Nei Ke Za Zhi. 2004 Jul;43(7):519-21
pubmed: 15312407
Immunol Lett. 2012 Sep;147(1-2):41-6
pubmed: 22743847
Cytokine. 2017 Oct;98:87-96
pubmed: 28438552
Gastroenterology. 2013 May;144(5):978-988.e10
pubmed: 23380085
Nat Genet. 2005 Dec;37(12):1317-9
pubmed: 16273109
Immunol Rev. 2016 Jan;269(1):212-27
pubmed: 26683155
Infect Immun. 2007 May;75(5):2244-52
pubmed: 17307945
Semin Immunol. 2006 Aug;18(4):207-13
pubmed: 16697661
Autoimmunity. 2001;34(2):107-13
pubmed: 11905840
Semin Immunol. 2009 Oct;21(5):293-300
pubmed: 19595612
Immunology. 2018 Jul;154(3):377-382
pubmed: 29512901
Annu Rev Immunol. 2014;32:83-119
pubmed: 24364806
Arthritis Rheum. 2010 Feb;62(2):383-91
pubmed: 20112361
Clin Immunol. 2012 Oct;145(1):13-8
pubmed: 22889643
Diabetes. 2004 Nov;53(11):3020-3
pubmed: 15504986
Rheumatol Int. 2016 Aug;36(8):1167-75
pubmed: 27324632
Genome Med. 2012 Feb 24;4(2):13
pubmed: 22364193
Eur J Immunol. 2018 Apr;48(4):655-669
pubmed: 29388193
Sci Signal. 2018 Apr 17;11(526):
pubmed: 29666305
Nat Genet. 2004 Apr;36(4):337-8
pubmed: 15004560
Genes Immun. 2012 Dec;13(8):641-52
pubmed: 23076337
Arthritis Res Ther. 2011;13(5):243
pubmed: 22078750
Immunol Res. 2009 Dec;45(2-3):144-58
pubmed: 19350211
J Clin Invest. 2011 Sep;121(9):3635-44
pubmed: 21804190