Serum Human Epididymis Protein 4 as a Novel Biomarker in Identifying Patients With Interstitial Lung Disease in Rheumatoid Arthritis.

Objective: Human epididymis protein 4 (HE4) have been implicated in the pulmonary involvements. We aimed to investigate the clinical utility of HE4 in clinical stratification in patients with rheumatoid arthritis (RA). Methods: This study included a discovery cohort comprising 70 RA patients and 64 healthy controls (HCs), and a validation cohort comprising 98 RA patients and 75 HCs. Human epididymis protein 4 were determined by electrochemical luminescence analyzer. Results: The levels of HE4 were significantly elevated in patients with RA compared to HCs. The positive rates of HE4 in patients with RA and HCs were 50.0% and 0, respectively, in the discovery cohort and 53.1 and 1.3%, respectively, in the validation cohort. When RA patients were subgrouped according to HE4 status, HE4-positive group displayed higher prevalence of interstitial lung disease (ILD) compared to HE4-negative group (28.6 vs. 11.4% in discovery cohort and 57.7 vs. 8.7% in the validation cohort). A positive correlation between the levels of HE4 with the degree of lung impairment was identified. Receiver operating curve (ROC) analysis revealed an optimal cut-off value of 104.3 pmol/L in HE4 for distinguishing RA-ILD from RA-non ILD with the areas under the curve (AUC) of 0.790. Multivariate logistic regression analysis illustrated that high levels of HE4 independently identified patients with RA-ILD (OR, 9.080, p < 0.001). Conclusion: Our findings showed a novel role of HE4 in RA risk stratification, suggest that introducing HE4 to the current RA test panel may serve as an indicator in identifying RA patients for further RA-ILD workups, such as high-resolution computed tomography (HRCT).

Liang L ，Chen J ，Di C ，Zhan M ，Bao H ，Xia C ，Fan C ，Liu Y ... -  《Frontiers in Medicine》

Human epididymis protein 4 as a new diagnostic biomarker for rheumatoid arthritis-associated interstitial lung disease.

Lin T ，Xu S ，Wang Y ，Nian X ，Shan X ，Jiang T ，Qiu M ... -  《CLINICAL AND EXPERIMENTAL RHEUMATOLOGY》

Elevated Serum Human Epididymis Protein 4 Is Associated With Disease Activity and Systemic Involvements in Primary Sjögren's Syndrome.

We aimed to investigate the clinical utility of human epididymis protein 4, a tumor biomarker being widely utilized in clinical practice in the diagnosis of ovarian cancer, in primary Sjögren's Syndrome (pSS). A total of 109 pSS patients and 113 healthy controls (HCs) were included in the study. HE4 were determined by Roche Cobas E601 electrochemical luminescence analyzer. Clinical and laboratory findings were reviewed, and the relationships between HE4 and clinical parameters were determined by Spearman's correlation test. The European league against rheumatism Sjögren's syndrome disease activity index (ESSDAI) was utilized to evaluate disease activity. The levels of HE4 were significantly elevated in patients with pSS compared to HCs (103.65 pmol/L vs. 46.52 pmol/L, p<0.001). The levels of HE4 were positively correlated with ESSDAI scores (r=0.462, p<0.001). Significant positive correlations between the levels of HE4 with pulmonary involvements (r=0.442, p<0.001) and renal involvements (r=0.320, p=0.001) were observed. Receiver operating curve (ROC) analysis revealed an optimal cut-off value of 104.90 pmol/L and 128.05 pmol/L for distinguishing patients with pulmonary and renal involvements, with the areas under the ROC curve (AUCs) of 0.778 (95%CI 0.685-0.870, p<0.001) and 0.768 (95%CI 0.646-0.891, p=0.001), respectively. Among patients with pulmonary involvement, the levels of HE4 were positively correlated with the semiquantitative HRCT grade (r=0.417, p=0.016), and negatively correlated with the percentage of forced vital capacity (FVC) (r= -0.460, p=0.047) and diffusing capacity of the lung for carbon monoxide (DLco) (r= -0.623, p=0.004). For patients with renal involvement, HE4 was positively correlated with creatinine (r=0.588, p=0.021) and negatively correlated with estimated glomerular filtration rate (r= -0.599, p=0.030). Our findings demonstrated a novel role of HE4 in clinical stratification of pSS, suggesting that introducing HE4 to the current pSS test panel may provide additional diagnostic value, particularly in evaluating disease activity and pulmonary/renal involvements.

Chen J ，Sun F ，Bao H ，Liang L ，Zhan M ，Yao H ，He J ，Liu Y ... -  《Frontiers in Immunology》

Human epididymis protein 4 as a clinical biomarker in identifying interstitial lung disease in patients with idiopathic inflammatory myopathies.

Human epididymis protein 4 (HE4) can differentiate interstitial lung disease from patients with some rheumatic diseases. However, the clinical utility of HE4 in idiopathic inflammatory myopathies (IIM) remains unclear. 80 IIM patients and 91 age and gender-matched healthy controls (HCs) were recruited. Clinical and laboratory data were recorded at baseline and 12 weeks. HE4 was tested by the method of electrochemical luminescence. Compared to HCs, the levels of HE4 significantly elevated in IIM patients. Patients with elevated HE4 had a higher interstitial lung disease (ILD) prevalence. Among patients with ILD, histological patterns of organizing pneumonia had higher HE4 levels than non-specific interstitial pneumonia. Further, there was a positive correlation between HE4 and the semi-quantitative CT grade (r = 0.778, p < 0.001) and a negative relation between HE4 and the percentage of forced vital capacity (p < 0.001) and diffusing capacity of the lung for carbon monoxide (DLco) (p = 0.001). An optimal cut-off value of HE4 (79.6 pmol/L) for distinguishing IIM-ILD was analyzed by ROC analysis with an AUC of 0.733 (p = 0.002). Regression analysis revealed that elevated HE4 independently identified IIM-related ILD (OR 34.8, 95 %CI, 3.58-338.14, p = 0.002). With the improvement after treatment, serum HE4 levels were significantly decreased (p = 0.006), accompanied by improved DLco% (p = 0.012). Serum HE4 was significantly elevated in patients with IIM and may be utilized as a serum biomarker to evaluate the disease severity and prognosis of IIM-related ILD.

Sun F ，Zhao J ，Li Y ，Wang H ，Cao X ，Cheng W ，Chen J ... -  《-》

Serum sCD25 is an indicator for rheumatoid arthritis-associated interstitial lung disease.

Cao S ，Liu X ，Li Y ，Yang Y ，Cai X ，Cong S ，Li Z ，Li Y ，Hong Y ，Su Y ，Li Z ，Luo L ，Sun X ... -  《CLINICAL AND EXPERIMENTAL RHEUMATOLOGY》