Background/Purpose: Lupus, a chronic autoimmune disease, is characterized by a variable clinical course, with periods of active disease termed flares. The severity of flares can be measured using clinical scores [SELENA-SLEDAI (SS); BILAG], but those scores do not define or suggest underlying pathophysiologic mechanisms of flare. Identification of a biomarker associated with clinical lupus flare would be useful for disease management, for assessment of response to therapeutic intervention in practice or clinical trials, and might suggest cellular or molecular targets for future therapies. To identify biomarkers that reflect lupus flare, we assessed longitudinal clinical and proteomic data from SLE patients.

Methods: One hundred sixty-nine plasma samples were collected longitudinally (up to 3 years) from 23 SLE patients and 5 healthy donors (HD), and SS and BILAG scores recorded. All SLE patients fulfilled ACR criteria for the disease. A panel of pro-inflammatory cytokines was evaluated using Multi-Analyte Profiling (MAP) technology (Rules-Based Medicine, Austin, TX). Longitudinal data analysis was performed using R (R Development Core Team) and the R packages lme4 and languageR. Data were analyzed using Linear Mixed Effects models (LME). A second validation set of 15 patients (175 visits) was used to confirm changes in the level of selected mediators in relation to clinical flare.

Results: Thirteen plasma factors were identified as significantly increased in SLE patients compared with HD, and 14 plasma factors were significantly deregulated during flaring compared with non-flaring visits, based on LME. However, in paired t-test analysis only von Willebrand factor (vWF) was significantly increased during severe flares compared to both first non-flaring visit before (p<0.02) and first non-flaring visit after (p<0.01) the identified flare. The association of changes in vWF with lupus flare was confirmed in the validation cohort.

Conclusion: vWF is produced by endothelial cells and is required for normal hemostasis and vascular function. Levels of circulating vWF are increased following endothelial cell damage and during acute phase responses. The significantly increased level of vWF during lupus flare in the majority of SLE patients highlights the role of endothelial injury as a major pathogenic mechanism in SLE and identifies vWF as an informative biomarker for patient management and clinical studies.

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/longitudinal-analysis-of-plasma-factors-and-disease-activity-identifies-von-willebrand-factor-as-a-biomarker-of-lupus-flare/