Nicolaou, OrthodoxiaSokratous, KleitosMakowska, ZuzannaMorell, MaríaDe Groof, AurélieMontigny, PaulineHadjisavvas, AndreasMichailidou, KyriakiOulas, AnastasisSpyrou, George M.Demetriou, ChristianaAlarcón-Riquelme, Marta E.Psarellis, SavvasKousios, AndreasLauwerys, BernardKyriacou, Kyriacos2022-10-282022-10-282020-06-18Nicolaou O, Sokratous K, Makowska Z, Morell M, De Groof A, Montigny P, et al. Proteomic analysis in lupus mice identifies Coronin-1A as a potential biomarker for lupus nephritis. Arthritis Res Ther. 2020 Jun 18;22(1):1476http://hdl.handle.net/10668/4296Background: Approximately 50% of systemic lupus erythematosus (SLE) patients develop nephritis, which is among the most severe and frequent complications of the disease and a leading cause of morbidity and mortality. Despite intensive research, there are still no reliable lupus nephritis (LN) markers in clinical use that can assess renal damage and activity with a high sensitivity and specificity. To this end, the aim of this study was to identify new clinically relevant tissue-specific protein biomarkers and possible underlying molecular mechanisms associated with renal involvement in SLE, using mass spectrometry (MS)-based proteomics. Methods: Kidneys were harvested from female triple congenic B6.NZMsle1/sle2/sle3 lupus mice model, and the respective sex- and age-matched C57BL/6 control mice at 12, 24 and 36 weeks of age, representing presymptomatic, established and end-stage LN, respectively. Proteins were extracted from kidneys, purified, reduced, alkylated and digested by trypsin. Purified peptides were separated by liquid chromatography and analysed by high-resolution MS. Data were processed by the Progenesis QIp software, and functional annotation analysis was performed using DAVID bioinformatics resources. Immunofluorescence and multiple reaction monitoring (MRM) MS methods were used to confirm prospective biomarkers in SLE mouse strains as well as human serum samples. Results: Proteomic profiling of kidney tissues from SLE and control mice resulted in the identification of more tan 3800 unique proteins. Pathway analysis revealed a number of dysregulated molecular pathways that may be mechanistically involved in renal pathology, including phagosome and proximal tubule bicarbonate reclamation pathways. Proteomic analysis supported by human transcriptomic data and pathway analysis revealed Coronin-1A, Ubiquitin-like protein ISG15, and Rho GDP-dissociation inhibitor 2, as potential LN biomarkers. These results were further validated in other SLE mouse strains using MRM-MS. Most importantly, experiments in humans showed that measurement of Coronin-1A in human sera using MRM-MS can segregate LN patients from SLE patients without nephritis with a high sensitivity (100%) and specificity (100%). Conclusions: These preliminary findings suggest that serum Coronin-1A may serve as a promising non-invasive biomarker for LN and, upon validation in larger cohorts, may be employed in the future as a screening test for renal disease in SLE patients.enAtribución 4.0 Internacionalhttp://creativecommons.org/licenses/by/4.0/BiomarkersLupus nephritisLNSLELupusProteomicsMass spectrometryMiceSystemic lupus erythematosusBiomarcadoresNefritis lúpicaProteómicaEspectrometría de masasRatonesLupus eritematoso sistémicoMedical Subject Headings::Organisms::Eukaryota::AnimalsMedical Subject Headings::Check Tags::FemaleMedical Subject Headings::Organisms::Eukaryota::Animals::Chordata::Vertebrates::Mammals::Primates::Haplorhini::Catarrhini::Hominidae::HumansMedical Subject Headings::Organisms::Eukaryota::Animals::Chordata::Vertebrates::Mammals::Rodentia::Muridae::Murinae::MiceMedical Subject Headings::Organisms::Eukaryota::Animals::Animal Population Groups::Animals, Inbred Strains::Mice, Inbred Strains::Mice, Inbred C57BLMedical Subject Headings::Chemicals and Drugs::Macromolecular Substances::Polymers::Biopolymers::Microfilament ProteinsMedical Subject Headings::Disciplines and Occupations::Natural Science Disciplines::Biological Science Disciplines::Biochemistry::ProteomicsMedical Subject Headings::Diseases::Skin and Connective Tissue Diseases::Connective Tissue Diseases::Lupus Erythematosus, SystemicMedical Subject Headings::Diseases::Skin and Connective Tissue Diseases::Connective Tissue Diseases::Lupus Erythematosus, Systemic::Lupus NephritisMedical Subject Headings::Chemicals and Drugs::Enzymes and Coenzymes::Enzymes::Hydrolases::Peptide Hydrolases::Endopeptidases::Serine Endopeptidases::TrypsinMedical Subject Headings::Chemicals and Drugs::Amino Acids, Peptides, and Proteins::Peptides::Intracellular Signaling Peptides and Proteins::GTP-Binding Protein Regulators::Guanine Nucleotide Dissociation Inhibitors::rho-Specific Guanine Nucleotide Dissociation Inhibitors::rho Guanine Nucleotide Dissociation Inhibitor betaMedical Subject Headings::Disciplines and Occupations::Natural Science Disciplines::Biological Science Disciplines::Biology::Computational BiologyMedical Subject Headings::Anatomy::Urogenital System::Urinary Tract::KidneyMedical Subject Headings::Anatomy::Cells::Cellular Structures::Intracellular Space::Cytoplasm::Cytoplasmic Structures::Organelles::Cytoplasmic Vesicles::PhagosomesMedical Subject Headings::Analytical, Diagnostic and Therapeutic Techniques and Equipment::Investigative Techniques::Epidemiologic Methods::Data Collection::Vital Statistics::Morbidityresearch article32552896Acceso abierto10.1186/s13075-020-02236-61478-6362PMC7301983