Glycosphingolipid Levels in Urine Extracellular Vesicles Enhance Prediction of Therapeutic Response in Lupus Nephritis.

Autor: Troyer B; Department of Medicine, Rheumatology Division, Medical University of South Carolina, Charleston, SC 29425, USA., Rodgers J; Department of Medicine, Rheumatology Division, Medical University of South Carolina, Charleston, SC 29425, USA., Wolf BJ; Department of Public Health Sciences, Medical University of South Carolina, Charleston, SC 29425, USA., Oates JC; Department of Medicine, Rheumatology Division, Medical University of South Carolina, Charleston, SC 29425, USA.; Rheumatology Section, Ralph H. Johnson VA Medical Center, Charleston, SC 29403, USA., Drake RR; Department of Cell and Molecular Pharmacology and Experimental Therapeutics, Medical University of South Carolina, Charleston, SC 29425, USA., Nowling TK; Department of Medicine, Rheumatology Division, Medical University of South Carolina, Charleston, SC 29425, USA.
Jazyk: angličtina
Zdroj: Metabolites [Metabolites] 2022 Feb 01; Vol. 12 (2). Date of Electronic Publication: 2022 Feb 01.
DOI: 10.3390/metabo12020134
Abstrakt: The development of nephritis increases the risk of morbidity and mortality in systemic lupus erythematosus (SLE) patients. While standard induction therapies, such as mycophenolate mofetil (MMF) induce clinical remission (i.e., complete response) in approximately 50% of SLE patients with nephritis, many patients fail to respond. Therapeutic response is often not assessed until 6-12 months after beginning treatment. Those patients that fail to respond to treatment continue to accumulate organ damage, thus, there is a critical need to predict which patients will fail therapy before beginning treatment, allowing physicians to optimize therapy. Our previous studies demonstrated elevated urine, but not serum, glycosphingolipids (GSLs) in SLE patients with nephritis compared to SLE patients without nephritis, suggesting the urine GSLs were derived from the kidney. In this study, we measured the GSLs hexosylceramide and lactosylceramide in extracellular vesicles isolated from longitudinal urine samples of LN patients that were treated with MMF for 12 months. GSL levels were significantly elevated in the baseline samples (prior to treatment) of non-responders compared to complete responders. While a few other proteins measured in the whole urine were higher in non-responders at baseline, only GSLs demonstrated a significant ability to discriminate treatment response in lupus nephritis patients.
Databáze: MEDLINE