Elevated serum levels of human epididymis protein 4 in adult patients with proliferative lupus nephritis.

This study aimed to access whether serum human epididymis protein 4 (HE4) level could identify lupus nephritis (LN) pathological classes in adults and children. The serum HE4 levels of 190 healthy subjects and 182 patients with systemic lupus erythematosus (SLE) (61 adult-onset LN [aLN], 39 childhood-onset LN [cLN], and 82 SLE without LN) were determined using Architect HE4 kits and an Abbott ARCHITECT i2000SR Immunoassay Analyzer. Serum HE4 level was significantly higher in the aLN patients (median, 85.5 pmol/L) than in the patients with cLN (44 pmol/L, P < 0.001) or SLE without LN (37 pmol/L, P < 0.001), or the healthy controls (30 pmol/L, P < 0.001). Multivariate analysis showed that serum HE4 level was independently associated with aLN. Stratified by LN class, serum HE4 level was significantly higher in the patients with proliferative LN (PLN) than in those with non-PLN, and this difference was found only in aLN (median, 98.3 versus 49.3 pmol/L, P = 0.021) but not in cLN. Stratified by activity (A) and chronicity (C) indices, the aLN patients with class IV (A/C) possessed significantly higher serum HE4 levels than those with class IV (A) (median, 195.5 versus 60.8 pmol/L, P = 0.006), and this difference was not seen in the class III aLN or cLN patients. Serum HE4 level is elevated in patients with class IV (A/C) aLN. The role of HE4 in the pathogenesis of chronic lesions of class IV aLN needs further investigation.

Li L ，Xu H ，Le Y ，Li R ，Shi Q ，Zhu H ，Xu H ，Li L ，Liu M ，Wang F ，Zhang H ... -  《Frontiers in Immunology》

Increased serum human epididymis protein 4 is associated with disease activity and systemic involvement in pediatric-onset systemic lupus erythematosus.

Liu C ，Yan L ，Zhang M ，Duan Y ，Luo J ，Liu Z ，Liu T ，Tong J ，Jiang Y ... -  《Frontiers in Immunology》

Human Epididymis Protein 4: A Novel Biomarker for Lupus Nephritis and Chronic Kidney Disease in Systemic Lupus Erythematosus.

Human epididymis protein 4 (HE4) is an available tumor biomarker for detecting ovarian cancer. However, it is unknown if serum HE4 could be a novel biomarker for diagnosis of lupus nephritis (LN) and chronic kidney disease (CKD) in patients with systemic lupus erythematosus (SLE). This study enrolled 209 SLE patients, 75 patients with renal dysfunction without SLE and 32 healthy subjects. HE4 concentrations were analyzed by ELISA (enzyme-linked immunosorbent assay; Fujirebio Diagnostics, Sweden). The receiver operating characteristic (ROC) curves were constructed to assess diagnostic accuracy of HE4 for LN or CKD in SLE. Serum HE4 level was significantly higher in SLE patients than that in healthy controls (P < 0.001), especially for those with LN or CKD. It was also higher in patients with renal dysfunction without SLE than healthy controls (P < 0.001), while there was no significant difference between these patients and those with SLE with CKD (P = 0.73). Multivariate analysis showed significant association between increased HE4 and LN or CKD after controlling for confounders. ROC curves showed the cutoff values were 150.1 pM (sensitivity, 76.8%; specificity, 91.1%) for the diagnosis of LN in SLE and 233.9 pM (sensitivity, 92.9%; specificity, 93.5%) for CKD in SLE. Increased serum HE4 level is closely associated with the development of LN or CKD in SLE patients. Furthermore, it can be used as a novel and useful biomarker for diagnosis of LN or CKD.

Yang Z ，Zhang Z ，Qin B ，Wu P ，Zhong R ，Zhou L ，Liang Y ... -  《-》

Serum human epididymis protein 4 is a predictor for developing nephritis in patients with systemic lupus erythematosus: A prospective cohort study.

It has been demonstrated that serum human epididymis protein 4 (HE4) is a useful biomarker for differentiating lupus nephritis (LN) from systemic lupus erythematosus (SLE). However, it remains unclear whether HE4 can be used to predict the development of LN. A total of 74 SLE patients without LN were recruited between August 2008 and September 2013. Serum HE4 concentrations were measured by enzyme-linked immunosorbent assay. These patients were followed up from the date of SLE diagnosis to LN development or the end of the study. The receiver operating characteristics (ROC) curve was drawn to assess the predictive value of HE4 for the incidence of LN. In addition, Kaplan-Meier and Cox regression analyses were used to determine the prognostic factors for the incidence of LN. Serum HE4 levels significantly increased in patients who are positive for anti-dsDNA antibody, low C3 and the incidence LN (P < 0.05), and these were closely correlated with age, erythrocyte sedimentation rate (ESR) and the SLE disease activity index (SLEDAI) (P < 0.05). During the follow-up, 44 patients developed LN. The ROC curve revealed that for HE4 levels, the predictive performance for LN with 64.8 pM as an optimal cutoff yielded an AUC of 0.714, with a 95% confidence interval of 0.597-0.831, and a sensitivity and specificity of 81.8% and 53.3%, respectively. The Kaplan-Meier analysis revealed that LN occurred in 72% of high-HE4 patients and 33.3% of low-HE4 patients (P = 0.036). The univariate analysis revealed that anti-dsDNA antibody, low C3, SLEDAI and HE4 were significantly associated with the incidence of LN (P < 0.05). Multivariate Cox regression revealed that only SLEDAI and HE4 were independently associated with the incidence of LN. Elevated serum HE4 is significantly associated with a higher risk of incidence for LN, and may be a useful predictor for developing LN.

Ren Y ，Xie J ，Lin F ，Luo W ，Zhang Z ，Mao P ，Zhong R ，Liang Y ，Yang Z ... -  《-》

Analysis of clinical and laboratory characteristics and pathology of lupus nephritis-based on 710 renal biopsies in China.

Song K ，Liu X ，Liu J ，Yin Z ，Chen P ，Cai G ，Chen X ... -  《-》