Background/Purpose:  SLE is a waxing and waning disease characterized by immune dysregulation, major organ involvement, and disease flares. Identifying mechanistic mediators of altered disease activity would help prevent damage and improve disease management. This study seeks to identify markers that correlate with disease activity and distinguish SLE patients with impending flare.

Methods: As part of the SLE Influenza Vaccination Cohort, 28 European-American SLE patients who exhibited SELENA-SLEDAI defined flare at 6 (n=13) or 12 (n=15) weeks post-vaccination had pre-vaccination (BL) and post-vaccination disease flare (FU) plasma samples assessed for 52 soluble analytes using a multiplex bead-based assay or sandwich ELISA (BLyS and APRIL). Each SLE patient was matched by race, gender, age (± 5 years), and time of sample procurement to a unique SLE patient who did not exhibit disease flare (NF). Samples from a subset of 13 SLE patients with flare were compared to samples from the same SLE patients from another year where disease flare did not occur (self nonflare, SNF). Soluble mediator concentrations were compared between flare and NF/SNF groups and correlated with SELENA-SLEDAI disease activity scores. As a gauge of impending disease flare, a soluble mediator score was adapted from the Studies of the Aetiology of Rheumatoid Arthritis (SERA) study: BL soluble mediator values from flare and NF/SNF samples were log transformed, standardized, and weighted by their respective disease activity Spearman coefficients, with the resulting values summed for a total score.

Results: Pre-vaccination concentrations of 22 out of 52 analytes significantly correlated (p<0.04) with post-vaccination SELENA-SLEDAI disease activity scores, including multiple innate (IL-1α, IL-β, IFNβ) and adaptive (Th1, Th2, and Th17) cytokines, chemokines (IP-10, MCP-3), adhesion molecule (ICAM-1)  and TNF superfamily members (TNF-α, Fas, FasL, TNFRI, and TNFRII). Utilizing all 52 assessed analytes weighted by their correlation with disease activity, patients with impending disease flare had a median soluble mediator score of 4.14 (± 4.40) and were 13.8 times more likely to have a positive score (p < 0.0001, Fisher’s exact test) compared to NF SLE patients (-1.70 ± 4.64). In the subset of flare vs SNF samples, SLE patients with impending flare had a median score of 4.36 (± 7.41) and were 11.1 times more likely to have a positive score (p=0.0469) compared to SNF samples (-3.09 ± 8.47). Additionally, significantly higher levels (p< 0.04) of regulatory mediators TGF-β and IL-1RA were observed in NF/SNF samples compared to periods of impending flare.

Conclusion: Multiple innate, adaptive, and shed TNF members are altered and correlate with disease activity. A soluble analyte score created to reflect overall inflammation in SLE patients is not affected by influenza vaccine responses and serves as a promising approach for future prospective studies.

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/multiple-altered-soluble-inflammatory-mediators-correlate-with-disease-activity-and-mark-impending-disease-flare-in-european-american-lupus-patients/