Background/Purpose: Systemic lupus erythematosus (SLE) is a complex autoimmune disease marked by immune dysregulation. A comprehensive but cost-effective tool to track relevant mediators of altered disease activity would help improve disease management and prevent organ damage. The goal of this study was to identify critical components of a practical biometric to distinguish active from low lupus disease activity

Methods: SLE-linked immune mediators and autoantibodies were evaluated in 311 plasma samples from 198 patients with classified SLE procured on dates of low clinical disease (SLEDAI < 4, range 0-3, n=132) or more active disease (SLEDAI ≥ 4, range 4-30, n=179) as well as healthy controls (HC) matched for race, sex, and age (n=48). Thirty two soluble mediators and SLE-associated autoantibody specificities, including dsDNA, chromatin, Ro/SSA, La/SSB, Sm, SmRNP, and RNP, were assessed by multiplex bead-based assay or sandwich ELISA (BLyS, APRlL, and TGF-β). Soluble mediator levels were compared across clinical disease activity levels in conjunction with the presence of autoantibodies.

Results: Patients with low or active disease were similar in age, ethnicity, and sex. After adjusting for multiple comparisons (Bonferroni corrected p<0.0018), IL-6, IL-1α, IP-10, and IL-8 were significantly correlated with SLEDAI scores (Spearman r=0.179-0.253), yet 22/32 soluble mediators significantly correlated with the number of SLE-associated autoantibodies accrued, including those listed above, as well as SCF, IFN-α, IFN-γ, IL-17A, IL-10, MIG, MIP-1β, TNFRII, and BLyS (r=0.318 [IL-17A]-0.468 [IP-10]). The regulatory mediator IL-10 was highest in samples (p<0.05) from patients with low disease activity, while inflammatory mediators were highest in active disease samples with accrued autoantibody specificities (p<0.001). We integrated these findings to build a Lupus Disease Activity Immune Index (LDAII), calculated utilizing normalized (case vs. control) soluble mediator levels (n=32) weighted by the number of SLE-associated autoantibodies in each individual. The LDAII distinguished patients with clinically active (CA) vs. quiescent (CQ) disease who were either serologically (dsDNA binding and low complement) active (SA) or quiescent (SQ) (p<0.0001), whereby the number of accumulated autoantibodies (p<0.0001) as well as IL-6, IL-8, and IP-10 levels (p≤0.0006) were most significantly altered. In addition, the LDAII was able to differentiate clinically and serologically quiescent (CQSQ) SLE patients vs. HC (p=0.019). Finally, the LDAII significantly correlated with SLEDAI scores in patients (p<0.0001) and identified patients with renal organ involvement (p=0.002), in whom SCF, TNFRII, and MCP-1 were also most significantly altered (p≤0.005).

Conclusion: Clinically meaningful components of immunological profiles may help illuminate disease pathogenesis, guide therapy, improve clinical trial design, and detect serious autoimmune disease with subtle presentation.

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/innate-adaptive-and-tnf-superfamily-immune-pathways-inform-a-lupus-disease-activity-immune-index-that-characterizes-disease-activity-in-sle/