The presence of IFL3/4 rs12979860 C allele influences the in vitro IP-10 production by mononuclear cells from patients with systemic lupus erythematosus

Lupus. 2020 Apr;29(5):482-489. doi: 10.1177/0961203320909429. Epub 2020 Mar 2.

Abstract

Objective: To explore whether the IFNL3/4 rs12979860 genotype may influence serum levels or production of interferon-inducible protein-10 (IP-10) by peripheral blood mononuclear cells from patients with systemic lupus erythematosus (SLE).

Methods: Sixty-six patients with SLE and 22 healthy blood donors (controls) were included. The IFNL3/4 rs12979860 polymorphism was genotyped by real-time polymerase chain reaction. IP-10 levels in sera supernatants of IFNα stimulated peripheral blood mononuclear cells were measured by enzime-linked immunosorbent assay.

Results: Allelic frequencies were CC (29%), CT (52%) and TT (20%) in SLE, and CC (32%), CT (41%) and TT (27%) in healthy controls. Median serum IP-10 levels were higher in SLE patients than in controls (190.8 versus 118.1 pg/ml; p < 0.001), particularly in those with high disease activity (278.5 versus 177.2 pg/ml; p = 0.037). However, serum IP-10 levels were not influenced by IFNL3/4 genotypes. Higher IP-10 production by peripheral blood mononuclear cells was found in both SLE patients (median 519.3 versus 207.6 pg/ml; p = 0.012) and controls (median 454.0 versus 201.7 pg/ml; p = 0.034) carrying the IFNL3/4 C allele compared with carriers of the T allele.

Conclusions: Although IFNL3/4 rs12979860 allele C does not appear to influence serum IP-10 levels in SLE, it plays an important role in the production of IP-10 by peripheral blood mononuclear cells after IFNα stimulation.

Keywords: IFNL3/4 rs12979860; IP-10; Systemic lupus erythematosus; interferon.

MeSH terms

  • Adult
  • Alleles
  • Case-Control Studies
  • Chemokine CXCL10 / blood*
  • Female
  • Gene Frequency
  • Genetic Predisposition to Disease
  • Humans
  • Interferons / genetics*
  • Interleukins / genetics*
  • Leukocytes, Mononuclear / metabolism*
  • Lupus Erythematosus, Systemic / blood
  • Lupus Erythematosus, Systemic / genetics*
  • Male
  • Middle Aged
  • Polymorphism, Single Nucleotide

Substances

  • CXCL10 protein, human
  • Chemokine CXCL10
  • interferon-lambda, human
  • IFNL4 protein, human
  • Interleukins
  • Interferons