Comparative proteomics analysis of plasma protein in patients with neuropsychiatric systemic lupus erythematosus

Abstract

Background: The aim of this study was to evaluate serum biomarkers of systemic lupus erythematous (SLE) patients, with and without neuropsychiatric (NP) manifestation by high-resolution proteomic analysis.Methods: SLE patients with NP (NPSLE, n=9), SLE patients without NP (non-NPSLE, n=9) and healthy controls (HC, n=9) were prospectively enrolled in this study, and their plasma samples were collected and pooled into 3 NPSLE, 3 non-NPSLE and 3 HC samples for discovery profile. The TMT-LC-MS/MSbased proteomics approach was used to identify the differential proteome among the three matched groups, and the data were analyzed by bioinformatics tools, including Gene Ontology (GO) categories, Kyoto Encyclopedia of Genes and Genomes enrichment analysis, to explore canonical pathways and networks involved in the pathogenesis of NPSLE. To validation of differentially expressed proteomics results, four proteins were measured by ELISA.Results: There were altogether 223 differentially expressed proteins in NPSLE groups compared with healthy controls (HC), of which 96 proteins increased while 127 proteins decreased. Compared with non-NPSLE, there were only 49 differentially expressed proteins in NPSLE groups, of which 37 proteins increased while 12 proteins decreased. The significantly changed pathway that those proteins are involved in was complement and coagulation cascades in NPSLE group compared with health controls. However, we didn't find significantly changed pathway between NPSLE group and non-NPSLE group. Five proteins were found significantly changed in all group-comparisons with consistent tendencies using Venn analysis, including Vitamin D binding protein (VDBP), C-reactive protein (CRP), KRT16, IGHV4-4 and CTRP3.Four proteins including CTRP3, VDBP, PAPPA and TRYP2 were selected to estimate the validity of the proteomics approach by ELISA. The expression levels of CTRP3 and TRYP2 were significantly changed in NPSLE patients compared with either HC or non-NPSLE patients. Conclusions: Our research has successfully established serum protein profiles of NPSLE and non-NPSLE patients through TMT technology and screened out five proteins significantly changed in groupcomparisons with consistent tendencies. The pathway of complement and coagulation cascades may participate in pathogenesis of NPSLE and non-NPSLE.

Multi-Platform Omics Analysis Reveals Molecular Signatures for Pathogenesis and Activity of Systemic Lupus Erythematosus

“…Previous studies have observed abnormal alterations in many mRNAs, proteins and metabolites in SLE patients. For example, elevated expression of CTRP3 and TRYP2, which might participate in the pathogenesis, were observed in plasma from neuropsychiatric SLE ( 21 ). Additionally, serum properdin, collectin-11 and thrombospondin-4 levels were able to monitoring the diseases activity of SLE patients ( 6 ).…”

Systemic lupus erythematosus: The search for the ideal biomarker

“…201 More than 200 proteins have been identified as potential biomarkers, some of them for SLE patients in general, but others for specific organs involved like LN or NPSLE. 202–204…”

Transcriptomics and quantitative proteomics reveal changes after second stimulation of bone marrow-derived macrophages from lupus-prone MRL/lpr mice

“…A growing number of researchers are turning to proteomics as a supply of novel biomarkers for a variety of disorders. Quantitative proteomics methods based on tandem mass tags (TMT) have been extensively employed to date for protein biomarker research and the assessment of protein modification in several autoimmune diseases and malignancies ( 26 ). The activation and control of inflammatory responses, as well as tissue homeostasis, are all mediated by macrophages.…”