Year: 2022
Type: article
Study design: Observational Study
Abstract: OBJECTIVE: Systemic lupus erythematosus (SLE) is marked by immune dysregulation linked to varied clinical disease activity. Using a unique longitudinal cohort of SLE patients, this study sought to identify optimal immune mediators informing an empirically refined flare risk index (FRI) reflecting altered immunity prior to clinical disease flare. METHODS: Thirty-seven SLE-associated plasma mediators were evaluated by microfluidic immunoassay in 46 samples obtained in SLE patients with an imminent clinical disease flare (preflare) and 53 samples obtained in SLE patients without a flare over a corresponding period (pre-nonflare). SLE patients were selected from a unique longitudinal cohort of 106 patients with classified SLE (meeting the American College of Rheumatology 1997 revised criteria for SLE or the Systemic Lupus International Collaborating Clinics 2012 revised criteria for SLE). Autoantibody specificities, hybrid SLE Disease Activity Index (hSLEDAI) scores, clinical features, and medication usage were also compared at preflare (mean ± SD 111 ± 47 days prior to flare) versus pre-nonflare (99 ± 21 days prior to nonflare) time points. Variable importance was determined by random forest analysis with logistic regression subsequently applied to determine the optimal number and type of analytes informing a refined FRI. RESULTS: Preflare versus pre-nonflare differences were not associated with demographics, autoantibody specificities, hSLEDAI scores, clinical features, nor medication usage. Forward selection and backward elimination of mediators ranked by variable importance resulted in 17 plasma mediator candidates differentiating preflare from pre-nonflare visits. A final combination of 11 mediators best informed a newly refined FRI, which achieved a maximum sensitivity of 97% and maximum specificity of 98% after applying decision curve analysis to define low, medium, and high FRI scores. CONCLUSION: We verified altered immune mediators associated with imminent disease flare, and a subset of these mediators improved the FRI to identify SLE patients at risk of imminent flare. This molecularly informed, proactive management approach could be critical in prospective clinical trials and the clinical management of lupus.
Source: Arthritis & Rheumatology
DOI: 10.1002/art.42389
Authors: Melissa E. Munroe, Derek Blankenship, Daniele DeFreese, Mohan Purushothaman, Wade DeJager, Susan Macwana, Joel M. Guthridge, Stan Kamp, Nancy Redinger, Teresa Aberle, Eliza F. Chakravarty, Cristina Arriens, Yanfeng Li, Hu Zeng, Kathleen A. McCarthy‐Fruin, Shirley‐Ann Osei‐Onomahm, Uma Thanarajasingam, Judith A. James, Eldon Jupe
Language: English
Subfield: Rheumatology
Field: Medicine
Domain: Health Sciences
Open Access status: green
Awards: Development of Immune Mediator Based Blood Tests that Inform Concurrent and Future Clinical Disease Activity in Systemic Lupus Erythematosus (SLE), G4851551467, An algorithm for predicting lupus flares informed by altered immune mediators, Translation of a diagnostic test for Lupus flare prediction from bench to clinic, Oklahoma ACE: Molecular Destruction of Autoimmune Disease to Aid Clinical Trail Success, Oklahoma Rheumatic Disease Research Cores Center, Commercialization Readiness of Immune Mediator Based Blood Tests that Inform Concurrent and Future Clinical Disease Activity in Systemic Lupus Erythematosus (SLE), Oklahoma Shared Clinical and Translational Resources, Immune Checkpoint Inhibition and humoral immune response in systemic autoimmunity
OpenAlex ID: W4306392856