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THU0040 Serum IFN Alpha, but not IFN Beta or IFN Omega, Correlates with IFN Signature in SLE Patients
  1. B.R. Lauwerys1,
  2. F.A. Houssiau1,
  3. P. Vandepapeliere2,
  4. F. Colaone2,
  5. P. Blanco3,
  6. T. Defrance4,
  7. G. Grouard-Vogel2
  1. 1Pôle de pathologies rhumatismales, Institut de Recherche Expérimentale et Clinique, Université catholique de Louvain and Service de Rhumatologie, Cliniques Universitaires Saint-Luc, Brussels, Belgium
  2. 2NEOVACS, Paris
  3. 3CHU Bordeaux, UMR/CNRS 5164, Bordeaux
  4. 4CIRI, Inserm U1111 - CNRS, Lyon, France

Abstract

Background Interferon-α-kinoid (IFN-K) elicits a polyclonal antibody response against IFNα in humans. In a previously reported study, we found that administration of IFN-K to SLE patients induces significant changes in biological markers of disease activity (IFN signature score, serum C3), which correlate with the anti-IFNα antibody (Ab) response. In the present study, we wanted to further explore the connections between serum type I IFN concentrations, IFN signature score and disease activity in IFN-K-treated patients.

Methods 28 patients (SLEDAI between 4 and 10) were included in the IFN-K trial, and received IFN-K or placebo. Whole blood transcriptome (GeneChip HGU133Plus 2.0 chips) and serum IFNα, IFNβ and IFNω concentrations (ELISA) were determined at day 0, 112 and 168. Whole blood transcriptomic profiles were also obtained in 46 healthy individuals, and in 18 of them after stimulation with IFNα. The IFN signature score was calculated according to the method described by Yao et al.

Results IFNα was detected in the serum of 10 out of 28 patients. IFNβ and IFNω were detected in 18 and 26 different patients, respectively. Serum IFNβ and IFNω concentrations displayed a strong correlation (r =0.88, p<0.0001), indicating that the production of both cytokines is regulated by the same mechanisms in SLE. By contrast, there was no correlation between serum IFNα and serum IFNβ or IFNω concentrations. Interestingly, a mucocutaneous BILAG A/B was more frequently reported at times of positive serum IFNβ detection (p =0.006 by Chi-Square test). There was a significant, albeit weak, correlation between serum IFNα and SLEDAI scores (Spearman r =0.26, p =0.02).

Strikingly, the IFN signature score displayed a strong and significant correlation with serum IFNα concentrations (Spearman r =0.54, p <0.0001), but not with serum IFNβ or IFNω. Out of the 54.675 probe sets analyzed in the whole blood transcriptomic studies, 349 correlated (r >0.4) with serum IFNα (including 19 out of the 21 probe sets included in the IFN signature score). By contrast, only 7 and 11 probe sets correlated with serum IFNβ and IFNω respectively.

We finally calculated an IFNα score including probe sets up-regulated by IFNα in control whole blood cells, and up-regulated in SLE compared to controls. Not surprisingly, this new IFNα score strongly correlates with the IFN signature score by Yao et al. Re-analysis of the IFN-K trial data using the new score confirmed the initial observations: higher production of anti-IFNα Ab in patients with a positive score, diminution of the IFNα score after administration of IFN-K, correlating with anti-IFNα Ab titers.

Conclusions IFNα, IFNβ and IFNω are detected in the sera of patients with SLE. IFNα and IFNβ/ω are not regulated similarly. Serum IFNβ is significantly associated with mucocutaneous involvement, while serum IFNα is higher in more active disease. The IFN signature score observed in SLE whole blood cells is driven by IFNα.

Disclosure of Interest : B. Lauwerys Consultant for: Neovacs, F. Houssiau Consultant for: Neovacs, P. Vandepapeliere Shareholder of: Neovacs, Employee of: Neovacs, F. Colaone Shareholder of: Neovacs, Employee of: Neovacs, P. Blanco Consultant for: Neovacs, T. Defrance Consultant for: Neovacs, G. Grouard-Vogel Shareholder of: Neovacs, Employee of: Neovacs

DOI 10.1136/annrheumdis-2014-eular.3713

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