PTPN22 1858C>T polymorphism is associated with increased CD154 expression and higher CD4+ T cells percentage in rheumatoid arthritis patients.

Autor: Ruiz-Noa Y; Instituto de Investigación en Ciencias Biomédicas, CUCS, Universidad de Guadalajara, Guadalajara, México., Hernández-Bello J; Instituto de Investigación en Ciencias Biomédicas, CUCS, Universidad de Guadalajara, Guadalajara, México., Llamas-Covarrubias MA; Instituto de Investigación en Ciencias Biomédicas, CUCS, Universidad de Guadalajara, Guadalajara, México., Palafox-Sánchez CA; Instituto de Investigación en Ciencias Biomédicas, CUCS, Universidad de Guadalajara, Guadalajara, México., Oregon-Romero E; Instituto de Investigación en Ciencias Biomédicas, CUCS, Universidad de Guadalajara, Guadalajara, México., Sánchez-Hernández PE; Departamento de Fisiología, Laboratorio de Inmunología, CUCS, Universidad de Guadalajara, México., Ramírez-Dueñas MG; Departamento de Fisiología, Laboratorio de Inmunología, CUCS, Universidad de Guadalajara, México., Parra-Rojas I; Facultad de Ciencias Químico-Biológicas, Universidad Autónoma de Guerrero, Chilpancingo, México., Muñoz-Valle JF; Instituto de Investigación en Ciencias Biomédicas, CUCS, Universidad de Guadalajara, Guadalajara, México.
Jazyk: angličtina
Zdroj: Journal of clinical laboratory analysis [J Clin Lab Anal] 2019 Mar; Vol. 33 (3), pp. e22710. Date of Electronic Publication: 2018 Nov 06.
DOI: 10.1002/jcla.22710
Abstrakt: 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: 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: 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: 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.
(© 2018 Wiley Periodicals, Inc.)
Databáze: MEDLINE
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