The Interferon Signature Correlates with Longitudinal Disease Severity in Systemic Lupus Erythematosus, but Adds Little to Conventional Prognostic Indicators

Arundip Asaduzzaman¹, Babak Noamani², Denisse Bonilla³, Dafna Gladman⁴, Murray Urowitz^5,6, Paul R. Fortin⁷, Carolina Landolt-Marticorena⁸ and Joan E. Wither⁹, ¹Rheumatology, Toronto Western Hospital, University of Toronto, Toronto, ON, Canada, ²Genetics and developmental biology, University Health Network, Toronto, ON, Canada, ³University Health Network, Toronto, ON, Canada, ⁴Rheumatology, University of Toronto, Toronto Western Hospital, Toronto, ON, Canada, ⁵University of Toronto, Toronto, ON, Canada, ⁶Rheumatology, U of Toronto, Toronto Western Hospital, Toronto, ON, Canada, ⁷Université Laval, CHU de Québec, Québec, QC, Canada, ⁸1E420/Div of Rheumatology, University Health Network, Toronto, ON, Canada, ⁹Rheumatology, University Health Network, Toronto, ON, Canada

Meeting: 2015 ACR/ARHP Annual Meeting

Date of first publication: September 29, 2015

Keywords: biomarkers and interferons, Lupus

Session Information

Date: Sunday, November 8, 2015

Title: Systemic Lupus Erythematosus - Clinical Aspects and Treatment Poster Session I

Session Type: ACR Poster Session A

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

Background/Purpose:

Type I interferon (IFN) is thought to play an important part in the pathophysiology of systemic lupus erythematosus (SLE), and cross-sectional data suggests an association between IFN-induced gene expression and SLE disease activity. However, interest in the IFN signature as a clinical biomarker has been tempered by a lack of fluctuation with disease activity over relatively brief durations (1-2 years) of follow up. In previous work we observed a significant reduction in the IFN signature in patients who had achieved prolonged clinical remissions off prednisone and immunosuppressives, as compared to relapsing and remitting SLE patients. This led us to question whether the IFN signature could act as a prognostic marker of disease severity.

Methods:

IFN induced gene expression was measured in the whole peripheral blood at baseline in 73 SLE patients, using nCounter (NanoString) multiplexed profiling. The expression levels of five representative interferon responsive genes were summed to yield a composite IFN-5 score. Adjusted mean SLEDAI-2K, number of flares, mean steroid dose, immunosuppressive use, and change in SLICC/ACR damage index (SDI) were obtained for all patients over the subsequent five year period. Clinical outcomes were compared to the baseline IFN-5 score by linear regression.

Results:

Of the 73 patients, 65 patients completed five years of follow-up, with 3 patients dying over the study period. As observed in previous studies, the IFN-5 score was positively associated with baseline disease activity (p=0.0007) and negatively associated with baseline age (p=0.004) and disease duration (p=0.003). Upon analysis of clinical outcomes over the subsequent 5 years, the baseline IFN-5 score demonstrated a significant positive association with the adjusted mean SLEDAI at the end of the study period (p=0.003), number of flares (p=0.03), and number of immunosuppressives used (p=0.03). There was also a positive trend between the IFN-5 score and mean steroid dose (p=0.23) and progression of damage (p=0.46). However, in a multivariate analysis incorporating conventional prognostic indicators including age, baseline disease activity, disease duration, immunosuppressive use, and the IFN-5 score, only age and baseline disease activity were independently associated with the outcome as measured by the adjusted mean SLEDAI-2K.

Conclusion:

Although higher interferon scores correlate with several clinical markers of increased disease severity over the subsequent 5 years, they do not appear to be independently associated with disease severity. This suggests that measurement of the interferon signature may be of limited utility as a prognostic biomarker.

Disclosure: A. Asaduzzaman, None; B. Noamani, None; D. Bonilla, None; D. Gladman, None; M. Urowitz, None; P. R. Fortin, None; C. Landolt-Marticorena, None; J. E. Wither, None.

To cite this abstract in AMA style:

Asaduzzaman A, Noamani B, Bonilla D, Gladman D, Urowitz M, Fortin PR, Landolt-Marticorena C, Wither JE. The Interferon Signature Correlates with Longitudinal Disease Severity in Systemic Lupus Erythematosus, but Adds Little to Conventional Prognostic Indicators [abstract]. Arthritis Rheumatol. 2015; 67 (suppl 10). https://acrabstracts.org/abstract/the-interferon-signature-correlates-with-longitudinal-disease-severity-in-systemic-lupus-erythematosus-but-adds-little-to-conventional-prognostic-indicators/. Accessed .

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