Anna Truszewska1,2, Agnieszka Wirkowska1, Kamila Gala1, Piotr Truszewski3, Łucja Krzemień-Ojak4, Agnieszka Perkowska-Ptasińska5, Krzysztof Mucha1,6, Leszek Pączek1,6, Bartosz Foroncewicz1. 1. Department of Immunology, Transplantology and Internal Diseases, Medical University of Warsaw, Warsaw, Poland. 2. Postgraduate School of Molecular Medicine, Medical University of Warsaw, Warsaw, Poland. 3. Department of Orthopedics and Traumatology of Musculoskeletal System, Baby Jesus Clinical Hospital, Warsaw, Poland. 4. Laboratory of the Molecular Biology of Cancer, Centre of New Technologies, Warsaw, Poland. 5. Department of Transplantology, Nephrology and Internal Medicine, Medical University of Warsaw, Warsaw, Poland. 6. Institute of Biochemistry and Biophysics, Polish Academy of Sciences, Warsaw, Poland.
Abstract
BACKGROUND: Increased level of cell-free DNA (cf-DNA) is associated with systemic lupus erythematosus (SLE) and might be related to disease activity. The aim of this study was to evaluate whether cfDNA integrity, size distribution and concentration of different cfDNA fractions is associated with lupus activity and kidney involvement. METHODS: Blood samples were collected from 43 SLE patients and 50 healthy controls. Nuclear and mitochondrial fractions of cfDNA and intracellular DNA were quantified by real-time qPCR. Sizing and quantification of total cfDNA level was performed on Bioanalyzer. RESULTS: We determined four parameters that characterized cfDNA profile: fragmentation index, ratio of intra- to extracellular mtDNA copy number, cfDNA concentration, and presence of 54-149 bp and 209-297 bp fragments. Patients with healthy-like cfDNA profile had higher eGFR (P = 0.009) and more often no indications for kidney biopsy or less advanced lupus nephritis (LN) (P = 0.037). In contrary, SLE patients with distinct cfDNA profile (characterized by increased cfDNA concentration and fragmentation, higher discrepancy between intra- to extracellular mtDNA copy number, and the presence of 54-149 bp and 209-297 bp fragments) had lower eGFR (P = 0.005) and more often advanced LN or history of renal transplantation (P = 0.001). CONCLUSIONS: We showed that cfDNA profiling may help to distinguish SLE patients with renal involvement and severe disease course from patients with more favorable outcomes. We suggest cfDNA profile a promising SLE biomarker.
BACKGROUND: Increased level of cell-free DNA (cf-DNA) is associated with systemic lupus erythematosus (SLE) and might be related to disease activity. The aim of this study was to evaluate whether cfDNA integrity, size distribution and concentration of different cfDNA fractions is associated with lupus activity and kidney involvement. METHODS: Blood samples were collected from 43 SLEpatients and 50 healthy controls. Nuclear and mitochondrial fractions of cfDNA and intracellular DNA were quantified by real-time qPCR. Sizing and quantification of total cfDNA level was performed on Bioanalyzer. RESULTS: We determined four parameters that characterized cfDNA profile: fragmentation index, ratio of intra- to extracellular mtDNA copy number, cfDNA concentration, and presence of 54-149 bp and 209-297 bp fragments. Patients with healthy-like cfDNA profile had higher eGFR (P = 0.009) and more often no indications for kidney biopsy or less advanced lupus nephritis (LN) (P = 0.037). In contrary, SLEpatients with distinct cfDNA profile (characterized by increased cfDNA concentration and fragmentation, higher discrepancy between intra- to extracellular mtDNA copy number, and the presence of 54-149 bp and 209-297 bp fragments) had lower eGFR (P = 0.005) and more often advanced LN or history of renal transplantation (P = 0.001). CONCLUSIONS: We showed that cfDNA profiling may help to distinguish SLEpatients with renal involvement and severe disease course from patients with more favorable outcomes. We suggest cfDNA profile a promising SLE biomarker.
Authors: Huiwen Che; Tatjana Jatsenko; Lore Lannoo; Kate Stanley; Luc Dehaspe; Leen Vancoillie; Nathalie Brison; Ilse Parijs; Kris Van Den Bogaert; Koenraad Devriendt; Sabien Severi; Ellen De Langhe; Severine Vermeire; Bram Verstockt; Kristel Van Calsteren; Joris Robert Vermeesch Journal: NPJ Genom Med Date: 2022-09-14 Impact factor: 6.083