Background/Purpose: Immune dysregulation propels systemic lupus erythematosus (SLE) pathogenesis. Capturing it as lab-based screening tests could help prioritize SLE patients for early intervention and proactive disease management. This study ascertained the usefulness of simultaneous Lupus Flare Risk Index (L-FRI) and Lupus Disease Activity Index (L-DAI) assessment to determine parallel risk of future clinical disease flare and concurrent disease activity.

Methods: L-FRI and L-DAI scores were calculated from 11 and 10 informing plasma mediators, respectively (Fig. 1) in 86 preflare (PF) vs. 87 prenonflare (PNF) visits, and 60 flare vs. 62 nonflare (NF) follow-up visits with available samples from a unique cohort of prospectively followed SLE patients. The algorithms reflect the sum of log-transformed/standardized informing immune mediators, weighted by their association with either ensuing disease activity at the time of future flare/NF (L-FRI) or a composite of current disease activity and SLE-associated autoantibody specificities (L-DAI). Hybrid SLEDAI (hSLEDAI) scores, clinical features, medication usage, and the presence of autoantibody specificities to dsDNA, chromatin, Ro/SSA, La/SSB, Sm, SmRNP, and RNP were also determined.

Results: Forty-three of 86 (50%) PF vs. 26 of 87 (30%) PNF visits were associated with active disease (hSLEDAI≥4; p=0.0084). The 43 PF and 61 PNF visits with low disease activity included 16 (PF)/10 (PNF) LLDAS and 14 (PF)/30 (PNF) in DORIS remission. The L-FRI did not differentiate disease activity itself (Fig 1A), but discerned flare risk in PF vs. PNF (Fig. 1A) and Flare vs. NF visits (Fig. 1B), irrespective of disease activity state. The L-DAI did not differentiate flare risk itself (Fig. 1C), but differentiated concurrent active vs. low (hSLEDAI< 4) disease activity, irrespective of flare risk status (Fig.1C-D). All SLE scores were higher than matched controls (p< 0.0001, Fig. 1). Plasma levels of osteopontin and BLyS (L-FRI, L-DAI), as well as other L-FRI informing mediators TNF-α, TNFRI, TNFRII, MCP-1, and MCP-3, were highest in PF visits with active disease (p< 0.05), while IL-17A levels were highest in PF visits with low disease activity and IL-4 highest in PNF visits with active disease (p< 0.05), Fig. 2. IL-7 (L-FRI, L-DAI) and TRAIL (L-DAI) levels were increased with both flare and disease activity risk (p< 0.05), while L-DAI informing mediators IFN-α, IFN-γ, IP-10, and IL-10 were highest in active disease (PF >PNF levels, p< 0.05), Fig 2. Of note, the L-FRI and L-DAI performed well at assessing flare and disease activity risk, respectively (AUC >0.8), yet parallel assessment of L-FRI and L-DAI performed better than either alone to identify simultaneous risk of concurrent active disease and imminent flare risk, Table 1.

Conclusion: Simultaneous use of the L-FRI and L-DAI optimally identified risk of imminent lupus disease flare and concurrent active disease to identify SLE patients who may benefit from early intervention strategies. Such an approach would improve disease management and be advantageous in prospective clinical trials for study participant recruitment and assessment.

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/simultaneous-assessment-of-complementary-lupus-specific-immune-mediator-informed-indexes-improves-their-ability-to-concurrently-discern-current-disease-activity-and-future-flare-risk-in-systemic-lupus/