Circulating Type I, II and III Interferons (IFNs) Associate with IFN-Scores, but Define Distinct Subsets of Active SLE

Vilija Oke¹, Iva Gunnarsson¹, Jessica M. Dorschner², Agneta Zickert¹, Timothy B. Niewold³ and Elisabet Svenungsson¹, ¹Department of Medicine, Rheumatology Unit, Karolinska Institutet, Karolinska University Hospital, Stockholm, Sweden, Stockholm, Sweden, ²Division of Rheumatology and Department of Immunology, Mayo Clinic, Rochester, MN, ³Colton Center for Autoimmunity, New York University, New York, NY

Meeting: 2017 ACR/ARHP Annual Meeting

Date of first publication: October 19, 2017

Keywords: autoantibodies and interferons, Disease Activity, Late-Breaking 2017, SLE

Session Information

Date: Tuesday, November 7, 2017

Title: ACR Late-Breaking Abstract Poster

Session Type: ACR Late-breaking Abstract Session

Session Time: 9:00AM-11:00AM

Background/Purpose:

Serum induced IFN gene expression (IFN-score) is considered a golden standard to assess IFN activity in SLE. So far, IFN-scores have not been compared to serum levels of type I, II and III IFNs. The study aimed to investigate how IFN-scores and SLE manifestations relate to serum levels of IFNs type I(αs), II(γ) and III(λ1).

Methods:

461 SLE patients and 322 controls were included. IFN-score was measured by WISH cell assay. INF-αs and IFN-λ1 were measured by ELISA. IFN-γ was measured by MSD 30-plex assay.

Results:

SLE patients had higher IFN-scores and higher levels of IFN-αs, IFN-γ and IFN-λ1 (p<0.001). IFN-scores correlated with levels of IFN-γ and IFN-α (ρ=0.39, and ρ=0.25, p<0.0001). Further, patients were grouped according to the high levels (≥3^rd quartile) of each IFN/IFN-score. The group with high IFN-scores had higher disease activity (SLAM, SLEDAI): weight loss (41%), fatigue (33%), fever (39%), rash (44%), lymphadenopathy (45%), arthritis (40%), nephritis (55%)(p<0.01). Interestingly, incidence of neuropsychiatric SLE, antiphospholipid (aPL) antibodies (abs), and also damage score was lower (p<0.05).

The characteristics of IFN-γ high group included higher disease activity (SLAM, SLEDAI), and specifically: active nephritis (52%), lymphadenopathy (40%), arthritis (42%), lymphopenia (37%), anemia (35%) and positivity for Sm (41%), SmRNP (36%) and RNP68 (45%), Ro52 (35%) and Ro60 (33%)(p<0.03).

The common features of IFN-α high group included younger age, shorter disease duration, active rash (34%), lymphadenopathy (43%), Ro52 (38%) and La (43%)(p=0.01). Presence of aPL abs and previous vascular events were lower and renal affection was uncommon (p<0.01).

In general, high IFN-scores reflected SLE manifestations that could be further stratified by high IFN-γ levels and to a lesser extent by high IFN-α. High IFN-λ1 did not define any phenotype of active SLE, except presence of anti-nucleosome abs.

Conclusion:

We demonstrate that high IFN-score associate more strongly with type II rather than type I IFNs. Importantly, major manifestations of SLE: active nephritis and arthritis, and also anti-Sm/SmRNP antibodies associate with IFN-γ; while rash associate with IFN-α.

Our findings are of major importance while tailoring clinical trials with anti-IFN therapies and demonstrate that importance of IFN-γ has so far been underscored.

Disclosure: V. Oke, None; I. Gunnarsson, None; J. M. Dorschner, None; A. Zickert, None; T. B. Niewold, None; E. Svenungsson, None.

To cite this abstract in AMA style:

Oke V, Gunnarsson I, Dorschner JM, Zickert A, Niewold TB, Svenungsson E. Circulating Type I, II and III Interferons (IFNs) Associate with IFN-Scores, but Define Distinct Subsets of Active SLE [abstract]. Arthritis Rheumatol. 2017; 69 (suppl 10). https://acrabstracts.org/abstract/circulating-type-i-ii-and-iii-interferons-ifns-associate-with-ifn-scores-but-define-distinct-subsets-of-active-sle/. Accessed .

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