THU0231 GELSOLIN A NEW BIOMARKER OF DISEASE ACTIVITY IN SLE PATIENTS ASSOCIATED WITH HDL-C

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Background: Recent proteomics techniques have demonstrated that high-density lipoprotein (HDL) associated proteins are involved in functions related to systemic inflammatory and immune responses in several pathological conditions, including autoimmune diseases. HDL undergoes structural and functional modifications in systemic lupus erythematous (SLE) patients. Objectives: To identify potential biomarkers of disease activity analyzing the proteome of HDL particles from SLE patients in clinical remission and when they develop a flare compared to a healthy control group. Methods: Quantitative proteomic analyses of purified HDL were performed using Tandem Mass Tag (TMT) isobaric tag-labeling and nanoLC-Orbitrap (nLC-MS/MS) from 9 SLE patients in clinical remission when they developed a flare and from 9 healthy controls (9-9-9). We verified the identified proteins by Western blot and ELISA in a cohort of 104 SLE women patients, 46 healthy women and 14 SLE patients when developed a flare. Results: A total of 83 proteins associated with HDL were identified. We found 17 proteins with a significant fold-change (>1.1) compared with their levels in control patients. In lupus patients experiencing a flare compared with those in remission, we identified 4 proteins with a significant fold-change (C4, Indian Hedgehog protein, S100A8 and gelsolin). Plasma Gelsolin (pGSN) levels were decreased in the 104 SLE patients (176.02(74.9) mcg/l) compared with the control group (217.13(86.7)mcg/l); p =0.005 and when they developed a clinical flare (104.84(41.7)mcg/l); p = 0002). pGSN levels were associated with HDL-c levels (r =0.316, p Conclusion: The proteome cargo from HDL differentiates SLE patients from healthy controls. HDL from SLE patients carries proteins that are involved in the activation of the immune system. Decreased pGSN are associated with clinical disease activity in SLE patients. Antimalarial treatment and HDL-c are associated with higher levels of pGSN in SLE patients. pGSN is a potential biomarker of disease activity in SLE patients. Disclosure of Interests: None declared