Urine inter-alpha-trypsin inhibitor family-related proteins may serve as biomarkers for disease activity of lupus

J Clin Lab Anal. 2022 Sep;36(9):e24622. doi: 10.1002/jcla.24622. Epub 2022 Jul 23.

Abstract

Background: Systemic lupus erythematosus (SLE) is a chronic inflammatory disease involving multiple tissues. Inter-Alpha-Trypsin Inhibitor (ITI) family proteins have a role in maintaining tissue homeostasis, but their possible clinical significance in the SLE patients has not been reported. The aim of this study was to analyze and verify the expression of ITI-related proteins in the urine of SLE patients, further explore the features of these proteins in disease activity.

Methods: Based on label-free proteomics technology and bioinformatics technology, we analyzed the expression of ITI family-related proteins in the urine of lupus. Subsequently, Western-blot and targeted proteomics were used to qualitatively and quantitatively verify the expression of these proteins, respectively.

Results: A total of seven ITI family-related proteins were screened and identified; and six of these proteins were differentially expressed in the urine of SLE patients. Further quantitative analysis showed that the expressions of ITIH2, ECM1, and ITIH5 in urine between active SLE group and stable SLE group were consistent with the preliminary screening results. The expression of ITIH2 and ECM1 in the renal damage group were also consistent with the screening results. Moreover, ITIH2 and ECM1 have a good correlation with disease activity and have a certain correlation with renal damage.

Conclusions: In this exploratory study, we evaluated the expression of ITI family-related proteins in the urine of SLE and found that urine ITIH2 and ECM1 were closely related to SLE activity, especially kidney damage, providing an experimental basis for further exploration of the potential roles in monitoring lupus and lupus nephritis activity.

Keywords: disease activity; inter-alpha-trypsin inhibitor family; proteomics; systemic lupus erythematosus; urine.

MeSH terms

  • Alpha-Globulins
  • Biomarkers / urine
  • Extracellular Matrix Proteins
  • Humans
  • Lupus Erythematosus, Systemic* / diagnosis
  • Lupus Nephritis* / urine
  • Proteinase Inhibitory Proteins, Secretory

Substances

  • Alpha-Globulins
  • Biomarkers
  • ECM1 protein, human
  • Extracellular Matrix Proteins
  • ITIH5 protein, human
  • Proteinase Inhibitory Proteins, Secretory
  • inter-alpha-inhibitor