Sandra Parra1,2, Mercedes Heras2,3, Pol Herrero4, Nuria Amigó5, Esperanza Garcés1, Josefa Girona2,3, Xavier Correig5,6, Nuria Canela4, Antoni Castro1,2. 1. Autoimmune Diseases Unit, Internal Medicine Department, 'Sant Joan' University Hospital (Reus, Spain), Spain. 2. Institut Investigació Sanitaria Pere Virgili (IISPV), Universitat Rovira i Virgili (URV), Reus, Spain. 3. Unitat de Recerca de Lipids i Arteriosclerosis (URLA), 'Sant Joan' University Hospital (Reus-Spain), Spain. 4. Centre for Omic Science, Joint Unit Universitat Rovira i Virgili-Eurecat, Spain. 5. Department of Electronic Engineering, Universitat Rovira i Virgili (URV), Reus, Spain, Rovira i Virgili University, IISPV, Spain. 6. Spanish Biomedical Research Centre in Diabetes and Associated Metabolic Disorders (CIBERDEM), Madrid, Spain.
Abstract
OBJECTIVES: To identify potential biomarkers of disease activity analysing the proteome of high-density lipoprotein (HDL) particles from SLE patients in clinical remission and when they develop a flare compared with a healthy control group. METHODS: Quantitative proteomic analyses of purified HDL were performed using Tandem Mass Tag isobaric tag-labelling and nanoLC-Orbitrap (nLC-MS/MS) from nine SLE patients in clinical remission when they developed a flare and from nine 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 a flare developed. RESULTS: We found 17 proteins with a significant fold-change (>1.1) compared with the control group. In lupus patients experiencing a flare compared with those in remission, we identified four 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=0.002). pGSN levels were associated with HDL cholesterol levels (r = 0.316, P<0.001). Antimalarial treated patients showed significant higher levels of pGSN (214.56(88.94) mcg/l regarding 170.35(66.36) mcg/l); P = 0.017. CONCLUSION: Decreased pGSN are associated with clinical disease activity in SLE patients. Antimalarial treatment and HDL cholesterol are associated with higher levels of pGSN.
OBJECTIVES: To identify potential biomarkers of disease activity analysing the proteome of high-density lipoprotein (HDL) particles from SLEpatients in clinical remission and when they develop a flare compared with a healthy control group. METHODS: Quantitative proteomic analyses of purified HDL were performed using Tandem Mass Tag isobaric tag-labelling and nanoLC-Orbitrap (nLC-MS/MS) from nine SLEpatients in clinical remission when they developed a flare and from nine healthy controls (9-9-9). We verified the identified proteins by Western blot and ELISA in a cohort of 104 SLEwomenpatients, 46 healthy women and 14 SLEpatients when a flare developed. RESULTS: We found 17 proteins with a significant fold-change (>1.1) compared with the control group. In lupuspatients experiencing a flare compared with those in remission, we identified four proteins with a significant fold-change (C4, Indian Hedgehog protein, S100A8 and gelsolin). Plasma gelsolin (pGSN) levels were decreased in the 104 SLEpatients (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=0.002). pGSN levels were associated with HDL cholesterol levels (r = 0.316, P<0.001). Antimalarial treated patients showed significant higher levels of pGSN (214.56(88.94) mcg/l regarding 170.35(66.36) mcg/l); P = 0.017. CONCLUSION: Decreased pGSN are associated with clinical disease activity in SLEpatients. Antimalarial treatment and HDL cholesterol are associated with higher levels of pGSN.