Background/Purpose: SLE has important effects on health-related quality of life (HRQOL) and is not well correlated to disease activity. As most SLE patients in remission have a consistent interferon (IFN) signature, it is assumed that persistent fatigue and/or impaired HRQOL is mediated by insufficiently controlled IFN response. The objective of the study was to test whether blood transcriptomic IFN signatures were associated with HRQOL.

Methods: Patients fulfilling the ACR revised criteria for SLE were included at a referral center for autoimmune diseases and followed up prospectively. Each assessment included demographic, clinical and laboratory evaluations, as well as whole blood transcriptomic data (Illumina beadchips). Disease activity was evaluated by the SELENA-SLEDAI score. HRQOL was assessed at each visit by the self-administrated SF-36 questionnaire, which includes two summary scores, the Physical Component Summary (PCS) and the Mental Component Summary (MCS), and eight domains: physical function (PF), role physical (RP), bodily pain (BP), general health (GH), vitality (VT), social functioning (SF), role emotional (RE) and mental health (MH). SF-36 scores ranged from 0 to 100, with higher scores reflecting better HRQOL. Transcriptomic analyses were performed using the second generation of a modular framework. Three IFN modules defined the modular IFN score: M1.2, M3.4 and M5.12.

Results: 57 SLE patients were evaluated. Median age was 38 years (18-70), 86% were women and 88% were caucasian. Median SLEDAI was 4 (0-22). At inclusion, SLE was clinically quiescent in 27 (47%) patients, while 30 (53%) were experiencing a flare, with active lupus nephritis in 19 (33%). Compared to the French general population (n=18754, mean age of 42 years), SLE patients had a marked reduction of HRQOL in all SF-36 domains and summary scores (p<0.0001), with delta of SF-36 scores ranging from 6 (MCS) to 27 (RP). In univariate analysis, the 3 IFN modules showed no significant correlation with any of the SF36 domains except for SF (r=0.44, p<0.01; r=0.33, p<0.05; r=0.28, p<0.05 for M1.2, M3.4 and M5.12 respectively), revealing unexpectedly that the higher the IFN signature, the better SF score. In multivariate analysis, taking into account other parameters associated with HRQOL such as flares, age, ethnicity, smoking and renal severity (nephrotic syndrome), SF was independently associated with the IFN score (p = 0.027). Analyses restrained to only quiescent patients (n=27, defined as clinically quiescent patients with or without immunological activity) yielded greater association between IFN score and SF (for the 3 modules) as well as MH (for M3.4). Additional analysis on all samples from quiescent visits (n=51) confirmed the association between the 3 IFN modules activity and SF, as well as MH and BP.

Conclusion: Far from confirming our hypothesis, this study demonstrates an unexpected positive association between IFN signature and HRQOL in SLE patients. These findings, consistent with the absence of impact on fatigue or HRQOL of recently tested IFN-blockade strategies, needs to be confirmed by other studies.

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/unexpected-association-between-health-related-quality-of-life-and-the-blood-interferon-modular-transcriptional-signatures-in-patients-with-systemic-lupus-erythematosus/