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 ... -  《-》

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 ... -  《-》

Nonrenal and renal activity of systemic lupus erythematosus: a comparison of two anti-C1q and five anti-dsDNA assays and complement C3 and C4.

Julkunen H ，Ekblom-Kullberg S ，Miettinen A 《-》

Urine neopterin as a parameter of disease activity in patients with systemic lupus erythematosus: comparisons with serum sIL-2R and antibodies to dsDNA, erythrocyte sedimentation rate, and plasma C3, C4, and C3 degradation products.

Lim KL ，Jones AC ，Brown NS ，Powell RJ ... -  《-》

Association of Blood Concentrations of Complement Split Product iC3b and Serum C3 With Systemic Lupus Erythematosus Disease Activity.

To examine correlations between blood levels of complement split product iC3b and serum component C3 with clinically meaningful changes in disease activity in patients with systemic lupus erythematosus (SLE). A total of 159 consecutive patients with SLE, diagnosed according to the American College of Rheumatology or Systemic Lupus International Collaborating Clinics classification criteria, were enrolled in CASTLE (Complement Activation Signatures in Systemic Lupus Erythematosus), a prospective observational study. Patients with 1-7 study visits were included in this longitudinal analysis. In addition, 48 healthy volunteers were enrolled to establish a normal reference value for the ratio of blood iC3b to serum C3 concentrations. Serum C3 and C4 levels were measured by nephelometry, and blood iC3b levels were measured by a lateral flow assay. SLE disease activity was monitored with the Responder Index 50 instrument of the SLE Disease Activity Index 2000. Relative changes in the iC3b:C3 ratio, levels of anti-double-stranded DNA (anti-dsDNA) antibodies, and use of a supraphysiologic dose of prednisone (>7.5 mg/day) each independently correlated with SLE disease activity, as determined in multilevel multiple logistic regression analyses. Only the iC3b:C3 ratio was significantly associated with clinically meaningful improvements in disease activity among patients with SLE who were receiving a supraphysiologic dose of prednisone. The iC3b:C3 ratio outperformed C3 and C4 levels with regard to discriminating active SLE from inactive SLE, and major flares from no disease activity. The iC3:C3 ratio, anti-dsDNA antibody levels, erythrocyte sedimentation rate, and use of a supraphysiologic prednisone dose were each independently associated with the presence of lupus nephritis, whereas none of these measures was associated with SLE rash. The association of the iC3b:C3 ratio with lupus nephritis was independent of other observed clinical manifestations. The ratio of blood iC3b to serum C3 concentrations correlates with the extent of SLE disease activity and with clinically meaningful changes in disease activity in patients with SLE. Furthermore, the iC3b:C3 ratio may discriminate between active and inactive SLE, and between major flares and no active disease.

Kim AHJ ，Strand V ，Sen DP ，Fu Q ，Mathis NL ，Schmidt MJ ，Bruchas RR ，Staten NR ，Olson PK ，Stiening CM ，Atkinson JP ... -  《-》