Session Information
Session Type: Abstract Submissions (ACR)
Background/Purpose: SLE is a multifaceted autoimmune disease denoted by immune dysregulation that contributes to increased morbidity and mortality in part due to infectious complications. Vaccination against common infections, such as influenza, is recommended for SLE patients to decrease infection risk. Using a unique resource of SLE patients participating in an influenza vaccination protocol with samples available before and at the time of clinically-defined disease flare, this study seeks to identify biomarkers of disease flare.
Methods: Over 6 flu seasons, 101 unique SLE patients and 101 healthy controls (HC) were enrolled in the SLE Influenza Vaccination Cohort. Plasma samples were obtained on the day of vaccination (BL) and at 6 and 12 weeks post-vaccination (FU). Demographics, detailed clinical information (disease activity, medication use), serum autoantibody profiles, and antibody response to influenza were collected at each visit. BL and FU samples from 29 European American (EA) SLE patients who exhibited SELENA-SLEDAI defined disease flare at 6 (n=14) or 12 (n=15) weeks post-vaccination were tested. Each SLE patient was matched by race/gender/age (+/- 5 years)/time of sample procurement/ANA status at BL to a unique SLE patient who did not exhibit disease flare (NF), as well as to a HC. Samples from 14 (n=7 each at 6 and 12 weeks at FU) of 29 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). Plasma samples were tested for 52 soluble inflammatory mediators, including cytokines, chemokines, and soluble receptors using xMAP multiplex bead-based assay or sandwich ELISA (BLyS and APRIL).
Results: SLE patients who exhibited disease flare had significant (p ≤ 0.01) alterations in 23 soluble mediators at BL compared to unique NF/SNF patients and HC. Altered BL mediators were also seen at time of disease flare, usually with no significant change in analyte levels compared to BL. SLE patients who exhibited disease flare had significantly (p ≤ 0.01) higher levels of BL pro-inflammatory adaptive cytokines, including IL-2, IL-12, IFN-γ, IL-6, and IL-17 compared to NF/SNF SLE patients and HC. Of particular interest were increased TNFR family members at BL in flare SLE patients, including TNFRI, TNFRII, Fas, FasL, and CD40L. Regulatory cytokines, including IL-10 and TGF-β were significantly increased (p ≤ 0.01)at BL in SLE patients not exhibiting disease flare (NF/SNF) compared to flare SLE patients and HC. A number of analytes, including MIP-1α and BLyS, were significantly higher in SLE patients compared to HC, but no difference was seen between flare and NF/SNF in this cohort.
Conclusion: Shed TNF receptors and proinflammatory adaptive cytokines representing Th1, Th2 and Th17 pathways are elevated in lupus patients who flare within the next 6-12 weeks. These remain unaffected by influenza vaccine, suggesting their utility as resilient, predictive biomarkers of flare and that influenza vaccination itself does not further promote risk for flare.
Disclosure:
M. E. Munroe,
None;
J. R. Anderson,
None;
J. T. Merrill,
None;
J. M. Guthridge,
None;
V. C. Roberts,
None;
G. M. Air,
None;
L. F. Thompson,
None;
J. A. James,
None.
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ACR Meeting Abstracts - https://acrabstracts.org/abstract/altered-soluble-inflammatory-mediators-mark-impending-systemic-lupus-erythematosus-disease-flare-in-european-american-lupus-patients-who-receive-influenza-vaccination/