Coagulation cascade and complement system in systemic lupus erythematosus.

Yan Liang,Hai-Feng Pan,Rui-Xue Leng,Hua-Bao Xiong,Qin Zhang,Dong-Qing Ye,Chang-Hao Wu,Shang-Bo Xie,Yin-Guang Fan,Si Li,Yuan Hu

doi:10.18632/oncotarget.23206

Abstract

This study was conducted to (1) characterize coagulation cascade and complement system in systemic lupus erythematosus (SLE); (2) evaluate the associations between coagulation cascade, complement system, inflammatory response and SLE disease severity; (3) test the diagnostic value of a combination of D-dimer and C4 for lupus activity. Transcriptomics, proteomics and metabolomics were performed in 24 SLE patients and 24 healthy controls. The levels of ten coagulations, seven complements and three cytokines were measured in 112 SLE patients. Clinical data were collected from 2025 SLE patients. The analysis of multi-omics data revealed the common links for the components of coagulation cascade and complement system. The results of ELISA showed coagulation cascade and complement system had an interaction effect on SLE disease severity, this effect was pronounced among patients with excess inflammation. The analysis of clinical data revealed a combination of D-dimer and C4 provided good diagnostic performance for lupus activity. This study suggested that coagulation cascade and complement system become ‘partners in crime’, contributing to SLE disease severity and identified the diagnostic value of D-dimer combined with C4for lupus activity.

Highlights

Systemic lupus erythematosus (SLE) is a systemic autoimmune disease that is characterized by a diverse array of autoantibody production, immune complex deposition and tissue and organ damage [1]
This study suggested that coagulation cascade and complement system become ‘partners in crime’, contributing to systemic lupus erythematosus (SLE) disease severity and identified the diagnostic value of D-dimer combined with C4for lupus activity
Patients were recruited in 3 sets: the cohort I including 24 SLE patients for the multi-omics analyses, the cohort II including 112 SLE patients for the protein expression analysis and the cohort III including 2025 SLE patients for the biomarker identification analysis

Summary

Introduction

Systemic lupus erythematosus (SLE) is a systemic autoimmune disease that is characterized by a diverse array of autoantibody production, immune complex deposition and tissue and organ damage [1]. Previous studies have reported the dysregulation of coagulation and complementrelated genes and proteins in patients with SLE, suggesting that coagulation cascade and complement system have a role in pathogenic process of SLE [2, 3]. Most of these studies focused on individual molecules which limit sufficient insight into the complex disease, such as SLE. Technological advances in the expression profiling, such as transcriptomics, proteomics and metabolomics, have broadened the spectrum of detectable compounds [4] These technologies are beginning to be utilized in the study of SLE. To date no researcher has comprehensively integrated these diverse sets of data to study SLE

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