Proteomic Analyses Reveal Cystatin C Is A Potential Biomarker For Evaluation Of Systemic Lupus Erythematosus

Background:systemic lupus erythematosus(SLE)is an extremely complex autoimmune disease characterized by abnormal activation of immune cells,increased production of autoantibodies,complement activation,deposition of immune complexes,and multi-tissue organ damage.Kidney involvement occurs in approximately 50% of patients.This led to lupus nephritis(LN).SLE occurs mostly in women,which brings great harm to the marriage,employment and physical and mental health of patients.It is a major topic in the current medical field.Therefore,further elucidating the occurrence and development mechanism of SLE,discovering new biomarkers of SLE,and exploring new more effective and safer drug therapeutic targets and strategies for SLE have always been the direction of efforts of researchers in this field.Serum Cys C level in SLE patients is up-regulated,and serum Cys C level is associated with kidney damage,suggesting that Cys C may be a biomarker for early diagnosis and prognosis of SLE.Objective:The occurrence and development mechanism of SLE remains unclear,and accurate biomarkers are still lacking.This study aims to use quantitative proteomics to identify biomarkers to assess organ damage and disease activity in SLE patients.Methods:Proteomic analysis was performed using mass spectrometry in 15 patients with SLE and 15 age-matched healthy controls.Proteomic profiles were compared in four main subtypes: SLE with proteinuria(SLE-PN),SLE without proteinuria(SLE-non-PN),SLE with anti-ds DNA antibody positivity(SLE-DP),and SLE with anti-ds DNA antibody negativity(SLE-non-DP).Gene ontology biological process analysis revealed differentially expressed protein networks.Cystatin C(Cys C)levels were measured in200 patients with SLE using an immunoturbidimetric assay.Data were collected and analyzed to assess the correlation between SLE laboratory markers and serum Cys C levels.Results:Proteomic analysis showed that upregulated proteins in both the SLE-PN and SLE-DP groups were mainly mapped to neutrophil activation networks.Moreover,Cys C from neutrophil activation networks was upregulated in both the SLE-PN and SLE-DP groups.The associations of serum Cys C level with proteinuria,anti-ds DNA positivity,lower complement C3 levels,and SLE disease activity index score in patients with SLE were further validated in a large independent cohort.Conclusions:Neutrophil activation is more prominent in SLE with proteinuria and anti-ds DNA positivity,and Cys C is a promising marker for monitoring organ damage and disease activity in SLE.