Session Information
Session Type: Abstract Submissions (ACR)
Background/Purpose: Type I interferons play a role in the pathogenesis of systemic lupus erythematosus (SLE), but their mechanisms of action are still not fully understood. In this study, we measured serum concentrations of IFNα, IFNβ and IFNω in a cross-sectional cohort of SLE patients followed at a single center, and investigated whether they correlate with clinical or biological indices of disease activity. The link between serum IFNα and IFN signature in SLE whole blood cells was further evaluated in a prospective set of samples from patients included in the IFNα kinoid study.
Methods: Sera from 178 patients with SLE were harvested during a visit at the Lupus Clinic, and stored at -80°. Serum IFNα, IFNβ and IFNω were measured by ELISA. BILAG scores, serum C3 and double-stranded DNA antibody titers were retrieved from the medical records. Active mucocutaneous disease was defined based on the presence of a mucocutaneous BILAG A, B or C. Because persistent hematuria results in a renal BILAG B score, only renal BILAG A was considered for the definition of active renal disease. Whole blood transcriptome (GeneChip HGU133Plus 2.0 chips) and serum IFNα concentrations were determined at day 0, 112 and 168 in an additional cohort of 28 patients (SLEDAI between 4 and 10) included in the IFNα kinoid trial. Statistical analyses (Mann-Whitney tests and Spearman correlations) were performed using Prism 5.0 software.
Results
14 out of 178 patients had active renal disease, and 33 had active mucocutaneous disease. Ouf of them, 7 displayed both renal and mucocutaneous disease activity.
Serum IFNα and IFNβ, but not IFNω, were significantly higher in the presence of a renal BILAG A. However, when patients with simultaneous renal and mucocutaneous involvement were discarded, only serum IFNα remained significantly higher in the presence of active renal disease (median concentration 4.53 versus 0 pg/ml, p< 0.0001).
Similarly, serum IFNβ and IFNα, but not IFNω, were significantly higher in the presence of a mucocutaneous BILAG A, B and C. However, when patients with simultaneous mucocutaneous and renal involvement were discarded, only serum IFNβ remained significantly higher in the presence of active mucocutaneous disease.
There was a low, albeit significant correlation between serum IFNα and serum dsDNA titers or C3 concentrations. In the set of patients included in the IFNα kinoid trial, the IFN signature score displayed a strong and significant correlation with serum IFNα concentrations (Spearman r = 0.54, p< 0.0001).
Conclusion: Our data indicate for the first time that the type I interferon response in SLE is different according to the affected system. The IFN signature score observed in SLE whole blood cells is driven by IFNα. Increased IFNα in systemic and renal disease and IFNβ in mucocutaneous disease indicate that distinct pathogenic mechanisms are involved in these different manifestations of the disease.
Disclosure:
J. Ducreux,
None;
F. Colaone,
Neovacs’ employee,
3;
S. Nieuwland,
None;
P. Blanco,
Neovacs,
5;
T. Defrance,
Neovacs,
5;
P. Vandepapeliere,
Neovacs’ employee,
3;
G. Grouard-Vogel,
Neovac’s employee,
3;
F. A. Houssiau,
Neovacs,
5;
B. R. Lauwerys,
Neovacs,
5.
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ACR Meeting Abstracts - https://acrabstracts.org/abstract/dissection-of-the-type-i-interferon-response-in-systemic-lupus-erythematosus-serum-ifn%ce%b1-is-elevated-in-lupus-nephritis-and-correlates-with-ifn-score-ifn%ce%b2-is-elevated-in-mucocutaneous-dise/