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Autoimmunity. 2017 Dec;50(8):468-475. doi: 10.1080/08916934.2017.1412431. Epub 2017 Dec 11.

High expression of interleukine-1 receptor antagonist in rheumatoid arthritis: Association with IL1RN*2/2 genotype.

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a Instituto de Investigación en Ciencias Biomédicas, CUCS , Universidad de Guadalajara , Guadalajara , México.
b Servicio de Reumatología , O.P.D. Hospital Civil de Guadalajara "Fray Antonio Alcalde" , Guadalajara , México.
c Departamento de Fisiología, Laboratorio de Inmunología , CUCS, Universidad de Guadalajara , Guadalajara , México.
d Facultad de Ciencias Químico Biológicas , Universidad Autónoma de Guerrero , Chilpancingo , México.
e Departamento de Biología Molecular en Medicina, Laboratorio de Biología Molecular en Medicina , CUCS , Guadalajara , México.
f Departamento de Ciencias de la Salud, CUValles , Universidad de Guadalajara , Ameca , México.


Rheumatoid arthritis (RA) is an autoimmune disease characterized by inflammation and pro-inflammatory cytokines production. IL-1Ra is an anti-inflammatory cytokine codified by IL1RN gene that blocks IL-1 signalling. A VNTR polymorphism of 86 bp in IL1RN gene has been associated with RA risk and regulation of IL-1Ra expression. In this study, we determined mRNA and protein expression of IL-1Ra in RA patients and control subjects (CS). This study included 85 RA patients classified according to the ACR/EULAR 2010 criteria and 67 CS. Polymerase chain reaction was used to identify IL1RN VNTR polymorphism, the expression of sIL-1Ra (secreted isoform) mRNA was determined by SYBR Green-based real time quantitave-PCR assay, and IL-1Ra soluble levels quantification was evaluated by ELISA test. RA patients had higher soluble levels of IL-1Ra than CS (p < .01), sIL-1Ra mRNA expression was higher in RA patients compared to CS (p < .01). Carriers of IL1RN*2/2 homozygous genotype show increased IL-1Ra soluble levels compared to IL1RN*long/long and IL1RN*2/long genotypes (p < .05) in the CS group, whereas mRNA expression in carriers of IL1RN*2/2 genotype was 1.2 times higher compared to IL1RN*long/long genotypes in the same group. Regarding RA patients, high expression of sIL-1Ra mRNA on carriers of IL1RN*long/long genotype was observed. Nevertheless, in RA patients IL-1Ra soluble levels among genotypes did not show significant differences. High expression of IL-1Ra in RA patients under treatment or not with antirheumatic drugs was detected. Additionally, carriers of IL1RN*2/2 genotype had higher IL-1Ra expression than carriers of other genotypes.


IL-1Ra; IL1RN VNTR; expression; polymorphism; rheumatoid arthritis

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