RT Journal Article
T1 Proteomic analysis in lupus mice identifies Coronin-1A as a potential biomarker for lupus nephritis
A1 Nicolaou, Orthodoxia
A1 Sokratous, Kleitos
A1 Makowska, Zuzanna
A1 Morell, María
A1 De Groof, Aurélie
A1 Montigny, Pauline
A1 Hadjisavvas, Andreas
A1 Michailidou, Kyriaki
A1 Oulas, Anastasis
A1 Spyrou, George M.
A1 Demetriou, Christiana
A1 Alarcón-Riquelme, Marta E.
A1 Psarellis, Savvas
A1 Kousios, Andreas
A1 Lauwerys, Bernard
A1 Kyriacou, Kyriacos
K1 Biomarkers
K1 Lupus nephritis
K1 LN
K1 SLE
K1 Lupus
K1 Proteomics
K1 Mass spectrometry
K1 Mice
K1 Systemic lupus erythematosus
K1 Biomarcadores
K1 Nefritis lúpica
K1 Proteómica
K1 Espectrometría de masas
K1 Ratones
K1 Lupus eritematoso sistémico
AB Background: 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.
PB BioMed Central, Springer Nature
YR 2020
FD 2020-06-18
LK http://hdl.handle.net/10668/4296
UL http://hdl.handle.net/10668/4296
LA en
NO Nicolaou 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):1476
DS RISalud
RD Apr 7, 2025