Interferon Activity in Early and Established SLE: Interferon Score Is Lower in Early Disease and Not Seen without Antibodies to Extractable Nuclear Antigens

Alaa A A Mohamed^1,2,3, Md Yuzaiful Md Yusof^1,4, Yasser El-Sherbiny⁵, Paul Emery^5,6 and Edward M. Vital^2,5, ¹Leeds Institute of Rheumatic and Musculoskeletal Medicine, University of Leeds, Leeds, United Kingdom, ²NIHR Leeds Musculoskeletal Biomedical Research Unit, Leeds Teaching Hospitals NHS Trust, Leeds, United Kingdom, ³Rheumatology and Rhabilitation, Assiut University, Assiut, Egypt, ⁴NIHR Leeds Musculoskeletal Biomedical Research Unit,Leeds Teaching Hospital NHS Trust, Leeds University, Leeds, United Kingdom, ⁵Leeds Institute of Rheumatic and Musculoskeletal Medicine, Leeds University, Leeds, United Kingdom, ⁶3. NIHR Leeds Musculoskeletal Biomedical Research Unit, Leeds Teaching Hospital NHS Trust, Leeds University, Leeds, United Kingdom

Meeting: 2015 ACR/ARHP Annual Meeting

Date of first publication: September 29, 2015

Keywords: Interferon activity, SLE and early incomplete SLE

Session Information

Date: Sunday, November 8, 2015

Title: Systemic Lupus Erythematosus - Human Etiology and Pathogenesis Poster I

Session Type: ACR Poster Session A

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

Background/Purpose:

SLE patients have increased expression of interferon-stimulated genes (ISG) and multiple autoantibodies. Some patients initially present with early incomplete SLE (E-ILE) with ANA but not full SLE criteria. These patients may or may not progress to established SLE. To understand progression of autoimmunity, we compared autoantibodies and ISG expression between E-ILE and established SLE.

Methods:

We studied patients with SLE (≥4 ACR/SLICC criteria (n=86)), E-ILE (1-3 ACR/SLICC criteria including ANA <1 year (n=23)), RA (n=19), and age and sex matched healthy controls (n=20). 33 Type 1 ISGs were analysed in PBMCs using TaqMan®. Relative expression was In-transformed and normalised to HC (value – HC mean / HC SD) and summed to give a 33-gene-IFN score. Antibodies to dsDNA, Ro52, Ro60, La, Sm, RNP and Chromatin were analysed using Bioplex-2000. Two-way ANOVA was used to compare IFN score vs. presence of extractable nuclear antigens (ENA) between groups.

Results:

Descriptively there was a strong relationship between interferon score and diagnosis of SLE. Mean (95% CI) IFN score was 3.0 (-12.2, 18.2) in RA, which was not substantively different from the HC mean (0). IFN score was considerably higher than HC in SLE [45.6 (34.8, 56.3)]. In E-ILE, IFN score was intermediate [22.3 (0.9, 43.7)]. Formal statistical comparisons were not attempted due to the variation in sample sizes between the groups.

There was a strong relationship between autoantibody status and interferon score. Interferon score was significantly higher in those with positive ENA antibodies (all p<0.05) but did not differ according to anti-dsDNA status (Fig 1).

This relationship between ENA status and interferon score was stronger in E-ILE (mean score ENA negative -25.6 vs. positive 47.8) than in established SLE (negative 22.9 vs positive 59.7; interaction=0.099; Fig 2). Indeed, in ENA-negative E-ILE, mean interferon score was significantly lower than HC (p=0.027).

Conclusion:

ISG expression is increased in E-ILE in patients with antibodies to ENA, but is low in their absence. In established SLE, ISG expression is higher, and interferon activity is increased even in the absence of ENA antibodies. This suggests that during progression to established SLE there is increasing dysregulation of interferon activity. This may be due to: diversification of the antibody repertoire during progression (not measured by this assay), or because in established SLE IFN becomes stimulated by other immune mediators or tissue damage. Longitudinal follow up will help resolve this question.

Disclosure: A. A. A. Mohamed, None; M. Y. Md Yusof, None; Y. El-Sherbiny, None; P. Emery, Janssen R & D, LLC, 2; E. M. Vital, Roche Pharmaceuticals, 2,Roche Pharmaceuticals, GSK, UCB, Chugai, 5.

To cite this abstract in AMA style:

Mohamed AAA, Md Yusof MY, El-Sherbiny Y, Emery P, Vital EM. Interferon Activity in Early and Established SLE: Interferon Score Is Lower in Early Disease and Not Seen without Antibodies to Extractable Nuclear Antigens [abstract]. Arthritis Rheumatol. 2015; 67 (suppl 10). https://acrabstracts.org/abstract/interferon-activity-in-early-and-established-sle-interferon-score-is-lower-in-early-disease-and-not-seen-without-antibodies-to-extractable-nuclear-antigens/. Accessed .

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