Proteomic analysis in lupus mice identifies Coronin-1A as a potential biomarker for lupus nephritis

Abstract

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.

Characterization of Citrullination Sites in Neutrophils and Mast Cells Activated by Ionomycin via Integration of Mass Spectrometry and Machine Learning

“…These proteins were involved in nuclei decondensation and neutrophil extracellular trap (NET) formation. , For example, two peptides, one each from coronin-1A (CORO1A) and adipocyte plasma membrane-associated protein (APMAP), contained four citrullination sites. Coronin-1A is one of the proteins found in the synovial citrullinome of RA patients and is a potential biomarker of systemic lupus erythematosus (SLE) disease …”

Alport syndrome: Proteomic analysis identifies early molecular pathway alterations in Col4a3 knock out mice

“…The application of discovery proteomics to investigate kidney diseases such as AS provides the opportunity to gain a more comprehensive insight into disease pathogenesis and identify novel therapeutic targets. 19 In this study, proteomic profiling of kidney tissues from Col4a3 Of the 1960 detected proteins 415 were significantly dysregulated and of these, S100-A8 was the protein with the highest expression in kidneys from AS compared to WT mice (max FC, 14.7).…”

“…The application of discovery proteomics to investigate kidney diseases such as AS provides the opportunity to gain a more comprehensive insight into disease pathogenesis and identify novel therapeutic targets 19 …”

Clinical and Immunological Biomarkers for Systemic Lupus Erythematosus

“…The results suggest that L-valine, pyrimidine, erucamide, and L-leucine are excellent potential diagnostic biomarkers for SLE, and alterations of fecal metabolites are closely correlated with SLE [117]. Proteomic profiling of kidney tissues from SLE revealed that coronin-1A is a biomarker of LN, and the level of it in serum can distinguish LN patients from SLE patients without nephritis with 100% sensitivity and 100% specificity [118]. Moreover, granzyme B is increased in the serum and kidneys of patients with SLE, and it is correlated with a poor prognosis of LN [119].…”