title: Increased activity of interleukin-23/interleukin-17 cytokine axis in primary antiphospholipid syndrome.
abstract: The aim of the study was to investigate serum concentrations of interleukin (IL)-17 and IL-17-inducing cytokines IL-23 and transforming growth factor (TGF)-β, as well as IL-17 single nucleotide polymorphism (SNP) rs2275913 in patients with primary antiphospholipid syndrome (PAPS). We studied fifty patients with PAPS and fifty age- and sex-matched healthy controls. The cytokine levels were measured by ELISA, while the rs2275913 SNP located in promoter region of IL-17 gene was genotyped using real-time PCR. The significantly higher levels of IL-17 (p=0.002), IL-23 (p<0.001) and TGF-β (p=0.042) were found in PAPS patients (median 13.1, 9.4, and 125.6 pg/ml, respectively) compared to the control group (6.8, 4.9 and 44.4 pg/ml). There was a significant positive correlation between concentrations of IL-17 and IL-23 (r=0.540, p<0.001), but not between those of IL-17 and TGF-β. No statistically significant differences were observed in the distribution of genotypes and alleles of the IL-17 rs2275913 variants in patients with PAPS compared to healthy subjects. The blood concentrations of IL-17 did not differ in subjects with different rs2275913 genotypes or patients with or without antiphospholipid antibodies. Finally, a trend toward higher IL-17 levels (p=0.063) and the significantly higher IL-17 concentrations (p=0.012) were observed in PAPS patients with deep vein thrombosis and thrombocytopenia, respectively. These data demonstrate that IL-23/IL-17 axis, stimulated independently of TGF-β increase IL-17A gene polymorphism and antiphospholipid antibody production, might contribute to vascular manifestations of PAPS.
authors.affiliation: Medical Center Bezanijska Kosa, University of Belgrade, Belgrade, Serbia.
authors.forename: Dragana
authors.initials: D
authors.lastname: Popovic-Kuzmanovic
authors.forename: Ivana
authors.initials: I
authors.lastname: Novakovic
authors.forename: Ljudmila
authors.initials: L
authors.lastname: Stojanovich
authors.forename: Ivona
authors.initials: I
authors.lastname: Aksentijevich
authors.forename: Nevena
authors.initials: N
authors.lastname: Zogovic
authors.forename: Gordana
authors.initials: G
authors.lastname: Tovilovic
authors.forename: Vladimir
authors.initials: V
authors.lastname: Trajkovic
mesh_terms: D000328:Adult; D016736:Antiphospholipid Syndrome / Q000175:diagnosis / Q000235:genetics / Q000276:immunology*; D002478:Cells, Cultured; D004252:DNA Mutational Analysis; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D056726:Genetic Association Studies; D005838:Genotype; D006801:Humans; D020381:Interleukin-17 / Q000097:blood / Q000235:genetics / Q000276:immunology*; D053759:Interleukin-23 / Q000097:blood / Q000276:immunology*; D008213:Lymphocyte Activation / Q000235:genetics / Q000276:immunology; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D011401:Promoter Regions, Genetic / Q000235:genetics; D058504:Th17 Cells / Q000276:immunology*; D016212:Transforming Growth Factor beta / Q000097:blood / Q000276:immunology
chemical_list: D020381:Interleukin-17; D053759:Interleukin-23; D016212:Transforming Growth Factor beta