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THU0028 Type i interferon signature in the peripheral blood and CXCL4 plasma levels in patients with systemic sclerosis
  1. NI Vlachogiannis,
  2. V-K Bournia,
  3. A Nezos,
  4. PF Christopoulos,
  5. M Patsouras,
  6. PG Vlachoyiannopoulos,
  7. CP Mavragani,
  8. PP Sfikakis
  1. Joint Academic Rheumatology Program, National and Kapodistrian University of Athens Medical School, Athens, Greece

Abstract

Background Type I Interferon (IFN) pathway is activated in Systemic Sclerosis (SSc) and represents a therapeutic target currently being tested in clinical trials, while higher IFNα levels have been also associated with pulmonary fibrosis in these patients. On the other hand, in vitro experiments using plasmacytoid dendritic cells from patients with SSc suggest an interplay between the chemokine (C-X-C motif) ligand 4 (CXCL4), a potential biomarker in SSc, and type I IFN. [1]

Objectives To test the hypothesis that type I IFN-induced gene expression in the peripheral blood associates with particular clinical and laboratory features, including plasma CXCL4 levels, in patients with SSc.

Methods Forty six patients with limited and 19 with diffuse SSc (60/65 women, aged 54±14 years, disease duration ranging between 0.5–27 years) and 20 healthy controls were examined. Peripheral whole blood samples (3ml) were subjected to cDNA synthesis and the expression of 3 genes (IFIT1, MX1, IFI44) that are preferentially induced by type I IFN was quantified by real time PCR. Type I IFN individual scores were calculated as described [2]; scores were arbitrarily considered as high when exceeding the mean value plus 3SD of the corresponding healthy control scores. Plasma CXCL4 levels were determined by ELISA.

Results A high type I IFN score (i.e.>8) ranging from 8.4 to 145 was found in 21/65 (32.3%) patients with SSc, compared with none of 20 healthy controls (p:0.002). SSc patients with high type I IFN scores demonstrated higher erythrocyte sedimentation rate and lower diffusing lung capacity for carbon monoxide (DLCO) levels than the remaining patients (p:0.002 and p:0.02, respectively, by Mann-Whitney U test). Other disease variables, including extent of skin involvement and autoantibodies, were not associated with high type I IFN score. Individual type I IFN scores positively correlated with the corresponding CXCL4 plasma levels (Spearman's r: 0.53, p-value: 0.02).

Conclusions A prominent type I IFN signature was observed in the peripheral blood of one third of patients with SSc in association with upregulated inflammatory response, reduced DLCO levels and higher CXCL4 plasma levels. Further prospective data are required to establish the role of type I IFN as an additional novel biomarker in SSc.

References

  1. van Bon L, Affandi AJ, Broen J, et al. Proteome-wide analysis and CXCL4 as a biomarker in systemic sclerosis. N Engl J Med 2014;370:433–43. doi:10.1056/NEJMoa1114576.

  2. Nezos A, Gravani F, Tassidou A, et al. Type I and II interferon signatures in Sjogren's syndrome pathogenesis: Contributions in distinct clinical phenotypes and Sjogren's related lymphomagenesis. J Autoimmun 2015;63:47–58. doi:10.1016/j.jaut.2015.07.002.

References

Disclosure of Interest None declared

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