Serum IL-12p40: A novel biomarker for early prediction of minimal change disease relapse following glucocorticoids therapy

Mengqiu Bai; Jian Zhang; Xinwan Su; Xi Yao; Heng Li; Jun Cheng; Jianhua Mao; Xiayu Li; Jianghua Chen; Weiqiang Lin

doi:10.3389/fmed.2022.922193

Serum IL-12p40: A novel biomarker for early prediction of minimal change disease relapse following glucocorticoids therapy

Front Med (Lausanne). 2022 Nov 24:9:922193. doi: 10.3389/fmed.2022.922193. eCollection 2022.

Authors

Mengqiu Bai^{1

2

3}, Jian Zhang¹, Xinwan Su^{1

2}, Xi Yao¹, Heng Li¹, Jun Cheng¹, Jianhua Mao⁴, Xiayu Li¹, Jianghua Chen¹, Weiqiang Lin^{1

2}

Affiliations

¹ Kidney Disease Center, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China.
² Department of Nephrology, The Fourth Affiliated Hospital, International Institutes of Medicine, Zhejiang University School of Medicine, Jinhua, Zhejiang, China.
³ Institute of Translational Medicine, Zhejiang University School of Medicine, Hangzhou, Zhejiang, China.
⁴ Department of Nephrology, Children's Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, China.

Abstract

Background: Minimal change disease (MCD) has a high recurrence rate, but currently, no biomarker can predict its recurrence. To this end, this study aimed at identifying potential serum cytokines as valuable biomarkers for predicting the risk of MCD recurrence.

Materials and methods: Raybiotech 440 cytokine antibody microarray was used to detect the serum samples of eight relapsed, eight non-relapsed MCD patients after glucocorticoid treatment, and eight healthy controls. The differentially expressed cytokines were confirmed by enzyme-linked immunosorbent assay (ELISA) with serum samples from 29 non-relapsed and 35 relapsed MCD patients. The study used the receiver operating characteristic (ROC) curve analysis to investigate the sensitivity and specificity of a serum biomarker for predicting the MCD relapse.

Results: Serum IL-12p40 levels increased significantly in the relapsed group. The Area Under the ROC Curve (AUC) of IL-12p40 was 0.727 (95%CI: 0.597-0.856; P < 0.01). The RNA-sequencing analysis and qPCR assay performed on the IL-12 treated mouse podocytes and the control group showed increased expression of podocyte damage genes, such as connective tissue growth factor (CTGF), matrix metallopeptidase 9 (MMP9), secreted phosphoprotein 1 (SPP1), and cyclooxygenase-2 (COX-2) in the former group.

Conclusion: IL-12p40 may serve as a new biomarker for predicting the risk of MCD recurrence after glucocorticoid treatment, and it may be involved in the pathogenesis and recurrence of MCD.

Keywords: IL-12p40; biomarker; cytokines; glucocorticoids therapy; minimal change disease.