Plasma soluble tumor necrosis factor receptor I as a biomarker of lupus nephritis and disease activity in systemic lupus erythematosus patients

Abstract

Objectives

The goal of our study was to evaluate the potential role of sTNF-RI as a biomarker of renal involvement in SLE patients and active SLE.

Methods

The study sample consisted of two cohorts. The discovery cohort included 16 SLE patients without renal involvement (non-LN), 60 lupus nephritis (LN) patients and 21 healthy controls (HCs) and the replication cohort included 18 SLE non-LN patients, 116 LN patients and 36 HCs.

Results

The sTNF-RI levels differed significantly in the discovery cohort. The plasma sTNF-RI levels were higher in LN patients than in non-LN patients (p = .009) and HCs (p = 4 × 10⁻⁶). Plasma sTNF-RI levels were significantly higher in non-LN patients than in HCs (p = .03). The finding was confirmed in independent replication cohort (LNs vs. non-LN, p = 4.053 × 10⁻⁷; LNs vs. HCs, p = 2.395 × 10⁻¹⁸; non-LN vs. HCs, p = 2.51 × 10⁻⁴). The plasma sTNF-RI levels were associated with disease activity, renal function in SLE patients and urine protein in LN patients. The multivariate analysis revealed that high sTNF-RI was an independent risk factor for renal involvement. The multivariate logistic regression results suggested that high TNF-RI, high systolic blood pressure, high serum creatinine, low C4 and positive anti-dsDNA were independent risks of active SLE patients. A nomogram was constructed based on the results of multivariate logistic regression analysis and it was practical in predicting the risk of the active SLE patients. Immunohistochemistry suggested that the expression of TNF-RI in the kidney was increased.

Conclusions

Plasma sTNF-RI might be a good biomarker of renal involvement and disease activity in SLE patients.

Keywords:

• Systemic lupus erythematosus
• lupus nephritis
• tumor necrosis factor receptor
• disease activity

Author contributions

XR.L collected the samples, performed the data and wrote this manuscript. YY.Q, YF.Z, Y.C helped in the samples collection and data analysis. ZZ.Z designed the entire study, the provided partial financial support and expert advice. All the authors mentioned had read and approved this final version of the manuscript.

Disclosure statement

We declare that this study was conducted in the absence of any financial or commercial relationships that could be construed as a potential conflict of interest.

Data availability statement

The data that support the findings of this study are available on request from the first author and corresponding author underlying reasonable request.

Additional information

Funding

This work was supported by the National Science Foundation of China [grant number 81900643, 81873611]; the China Postdoctoral Science Foundation Grant [grant number 2019M652592]; the Postdoctoral Research Grant in Henan Province [grant number 1902005, 1901004]; the Science and Technology Innovation Team of Henan [grant number 17IRTSTHN020]; the Foundation for Leading Personnel of Central Plains of China [grant number 194200510006]; the Foundation for Medical Science and Technology Program of Henan [grant number 11195, 11272]; and the Henan Science and Technology Research Program [grant number SB201901048, 2018020102, 2018020142]. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.