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 ... -  《-》

Interferon-Inducible Protein 10 and Disease Activity in Systemic Lupus Erythematosus and Lupus Nephritis: A Systematic Review and Meta-Analysis.

Puapatanakul P ，Chansritrakul S ，Susantitaphong P ，Ueaphongsukkit T ，Eiam-Ong S ，Praditpornsilpa K ，Kittanamongkolchai W ，Avihingsanon Y ... -  《INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES》

Insulin-like growth factor binding protein-2 as a novel biomarker for disease activity and renal pathology changes in lupus nephritis.

Lupus nephritis (LN) is one of the most serious manifestations of systemic lupus erythematosus. Invasive renal biopsy remains the gold standard for the diagnosis and management of LN. The objective of this study is to validate serum insulin-like growth factor binding protein-2 (IGFBP-2) as a novel biomarker for clinical disease and renal pathology in LN. Eighty-five biopsy-proven lupus nephritis patients, 18 chronic kidney disease (CKD) patients and 20 healthy controls were recruited for enzyme-linked immunosorbent assay (ELISA) testing of serum IGFBP-2 levels. Compared to CKD patients of origins other than lupus or healthy controls, serum IGFBP-2 levels were elevated significantly in LN patients. Serum IGFBP-2 was able to discriminate LN patients from the other two groups of patients [area under the curve (AUC) = 0·65, 95% confidence interval (CI) = 0·52-0·78; P = 0·043 for LN versus CKD; 0·97, 95% CI = 0·93-1·00; P < 0·0001 for LN versus healthy controls]. Serum IGFBP-2 was a potential indicator of both global disease activity and renal disease activity in LN patients, correlated with serum creatinine levels (r = 0·658, P < 0·001, n = 85) and urine protein-to-creatinine levels (r = 0·397, P < 0·001, n = 85). More importantly, in 19 concurrent patient samples, serum IGFBP-2 correlated with the chronicity index of renal pathology (r = 0·576, P = 0·01, n = 19) but not renal pathological classification. In conclusion, serum IGFBP-2 is a promising biomarker for lupus nephritis, reflective of disease activity and chronicity changes in renal pathology.

Ding H ，Kharboutli M ，Saxena R ，Wu T ... -  《-》

Serum thiols as a biomarker of disease activity in lupus nephritis.

Lalwani P ，de Souza GK ，de Lima DS ，Passos LF ，Boechat AL ，Lima ES ... -  《PLoS One》