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 ... -  《-》

Insulin-Like Growth Factor Binding Protein-4 as a Marker of Chronic Lupus Nephritis.

Wu T ，Xie C ，Han J ，Ye Y ，Singh S ，Zhou J ，Li Y ，Ding H ，Li QZ ，Zhou X ，Putterman C ，Saxena R ，Mohan C ... -  《PLoS One》

Insulin-like growth factor binding protein-2 as a biomarker for lupus nephritis.

Lupus nephritis (LN) is a serious manifestation of systemic lupus erythematosus (SLE). The aim of this study was to identify serum insulin-like growth factor binding protein-2 (IGFBP-2) as a novel non-invasive biomarker for clinical disease and renal pathology in pediatric LN. A cross-sectional study on 93 newly diagnosed LN children who were biopsy-proven, 35 SLE children with no renal involvement as disease controls, and 30 healthy controls (HC) with age and gender-matched. All children were ELISA tested for serum IGFBP-2 levels. Clinical, laboratory, histopathological features of LN patients were collected. Compared to SLE or HC, serum IGFBP-2 levels were significantly elevated in LN patients. Serum IGFBP-2 could distinguish LN patients from two others (AUC = 0.937, p < 0.001 for LN vs. HC; 0.897, p < 0.0001 for LN vs. SLE). In ROC analysis, IGFBP-2 had a higher ability to differentiate between LN and SLE than anti-dsDNA with AUC values of 0.895 and 0.643, respectively. LN children with systemic lupus erythematosus disease activity index (SLEDAI) in high activity had significantly higher IGFBP-2 concentration than the others with SLEDAI in moderate activity. Serum IGFBP-2 correlated with albuminemia levels (r = 0.415, p < 0.001), urine protein-to-creatinine levels (r = 0.316, p = 0.002), estimated glomerular filtration rate (r = 0.438, p < 0.001), complement C3 (r = 0.333, p = 0.001). More importantly, serum IGFBP-2 correlated with the activity index of renal pathology (r = 0.312, p = 0.007, n = 75). Serum IGFBP-2 is a promising biomarker for pediatric lupus nephritis, reflective of disease activity and activity index in renal patients.

Luong PT ，Nguyen TTD ，Nguyen NT ，Ngo HT ，Nguyen HN ，Pho DH ，Nguyen HT ... -  《-》

Urine S100 proteins as potential biomarkers of lupus nephritis activity.

Turnier JL ，Fall N ，Thornton S ，Witte D ，Bennett MR ，Appenzeller S ，Klein-Gitelman MS ，Grom AA ，Brunner HI ... -  《-》

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 ... -  《-》