THU0277 THE EXPRESSION OF IFNΑ, INFΒ AND INFΓ AND SERUM LEVELS OF THOSE CYTOKINES IN SJÖGREN’S SYNDROME PATIENTS

Background: In the pathogensis of autoimmune mediated diseases, such as Sjögren’s syndrome (SS), interferons (IFN) and IFN pathway activation play a vital role. Objectives: We planned to assess IFNα, INFβ and INFγ expression and IFNs serum levels in SS patients and correlation of these parameters with: autoantibodies specific for SS, serum concentration of C3, C4 component of complement (C3, C4), rheumatoid factor (RF), gammaglobulins, focus score (FS) and eye dryness symptoms. Methods: Whole blood RNA was isolated from 77 SS patients [F91%vsM9%]; mean age 49,69±15.36; SS diagnosis according to EULAR/ACR 2016 criteria. The analysis of INFα, - β and - γ expression levels was based on validated TaqMan probes by ΔCT methods. Serum concentrations of rheumatoid factor (RF), C3- and C4 complement components (mg/dL) and gammaglobulins (g/dL), were assessed. Anti-Ro/SSA and/or anti-La/SSB autoantibodies were assessed by semiquantitative immunoblotting evaluation. The eye dryness and keratoconjunctivitis sicca were confirmed with Schirmer’s test (score of less than 5 mm/5’) and the ocular staining score (OSS) using lissamine green and fluorescein staining. The biopsy of minor salivary gland was performed with the histopathological evaluation of FS. The study was approved by the Bioethics Committee. Differences between groups of patients were determined using non-parametric Mann-Whitney U test or Kruskall-Wallis test with Dunn’s post hoc. Correlations were determined using non-parametric Spearman test. The level of statistical significance was set at p < 0.05. Results: IFNβ had the highest expression levels among IFNs and IFNβ serum concentrations were higher than those of IFNα and -γ. In cases with high IFNβ serum concentration lower IFNβ expression was observed. There was a highly significant correlation between IFNα and IFNβ expression (r =0.6;p=0.001). IFNβ expression (p=0.059) was higher in the group of younger (<45 y.o.) patients (n= 23; 29.9%) as compared to the group of older individuals (at least 45 y.o.). In patients with SS-A / Ro antibodies with strong antigen binding affinity (3) IFN β expression and IFNβ serum levels were highest of all IFNs. The presence of anti La/SS-B antibodies was associated with the increased IFNβ expression while not with the increased IFNβ serum concentration. In terms of IFNα expression and protein level, RF(+)patients had average higher values compared to RF(-) patients. The average mRNA level of IFNα was about 3 times lower in patients with low C3 serum concentration compared to patients with normal C3 serum concentration values. IFNβ mRNA level was 2.5 times lower in patients with low Schirmer’s test (<5mm/5’) in comparison to patients with Schirmer’s test>5mm/5’; Schirmer’s test <5mm/5’ was associated with higher IFNβ serum concentration. Conclusion: Type I IFN signature predominates in the peripheral blood of studied patients. Presented results confirmed the pivotal role of type I IFN in the disease process. The serum concentration of IFNβ and the expression of IFNβ were the highest values of those parameters for cytokines assessed in this study. A positive correlation between IFNα and IFNβ mRNA levels has been observed. Disclosure of Interests: None declared