Serum Human Epididymis Protein 4 and Its Correlation with Lupus Nephritis: A Prospective Cohort Study

Corresponding author: Zhang Limei, 3580955757@qq.com

DOI: 10.12201/bmr.202603.00110

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  Abstract: 【】Objective:Investigating the Clinical Value of Baseline Serum Human Epididymis Protein 4 Levels in Predicting Lupus NephritisMethods:A total of 120 newly diagnosed, incident systemic lupus erythematosus (SLE) patients without renal involvement were recruited from Qujing First People’s Hospital between December 2022 and December 2025. Serum samples were collected from all subjects, and human epididymis protein 4 (HE4) levels were measured by electrochemiluminescence immunoassay. Patients were prospectively followed, with the primary endpoint being clinical diagnosis of lupus nephritis (LN). Receiver operating characteristic (ROC) curve analysis was employed to evaluate the predictive performance of HE4. Cox proportional hazards regression models were used to identify independent risk factors for the development of LN.Results:Among the 120 patients enrolled in the study, 22 progressed to lupus nephritis (LN), with an incidence rate of 18.33%. Compared to the non-progressor group, the 22 patients in the progressor group exhibited higher baseline disease activity, characterized by significantly higher SLEDAI scores and anti-dsDNA antibody positivity rates, alongside significantly lower complement C3 and C4 levels (P < 0.05). The progressor group also showed poorer systemic inflammatory and nutritional status, with significantly elevated erythrocyte sedimentation rate (ESR) and reduced serum albumin levels (P < 0.05). Regarding biomarkers, serum HE4 levels were significantly higher in the progressor group than in the non-progressor group (P < 0.05). Correlation analysis revealed that baseline serum HE4 levels were positively correlated with disease activity indicators such as SLEDAI score, anti-dsDNA antibody titer, and ESR, and negatively correlated with complement C3, C4, and serum albumin levels (P < 0.05). The area under the curve (AUC) for serum HE4 in predicting LN was 0.828 (95% CI: 0.751–0.905), with an optimal cut-off value of 53.6 pmol/L. The combined model incorporating HE4, complement C3, and SLEDAI score demonstrated the best predictive performance, with an AUC of 0.875 (95% CI: 0.808–0.942).Conclusion:Elevated serum human epididymis protein 4 (HE4) is an independent predictor of lupus nephritis (LN) development in patients with incident systemic lupus erythematosus (SLE). Monitoring HE4 levels may facilitate the early identification of high-risk patients for LN.

  Key words: Systemic Lupus Erythematosus; Human Epididymis Protein 4; Lupus Nephritis; Clinical Prediction

  Submit time: 25 March 2026

  Copyright: The copyright holder for this preprint is the author/funder, who has granted biomedRxiv a license to display the preprint in perpetuity.
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