{Reference Type}: Journal Article
{Title}: Human epididymis protein 4 is associated with severity and poor prognosis of connective tissue disease-associated interstitial lung disease with usual interstitial pneumonia pattern.
{Author}: Meng K;Tian M;Gui X;Xie M;Gao Y;Shi S;Zhao T;Xiao Y;Cai H;Ding J;
{Journal}: Int Immunopharmacol
{Volume}: 108
{Issue}: 0
{Year}: Jul 2022
{Factor}: 5.714
{DOI}: 10.1016/j.intimp.2022.108704
{Abstract}: <B>BACKGROUND: </B>Overexpression of human epididymis protein 4 (HE4) was previously described in idiopathic pulmonary fibrosis (IPF), but whether serum HE4 can be considered as a potential biomarker in connective tissue disease-associated interstitial lung disease (CTD-ILD) with usual interstitial pneumonia (UIP) pattern was still unknown.<BR><B>METHODS: </B>A total of 55 CTD-ILD patients with UIP pattern (UIP-CTD) and 52 healthy controls were enrolled in this study. The serum levels of HE4 and Krebs von den Lungen-6 (KL-6) were evaluated in both cohorts. In addition, immunohistochemistry analysis for HE4 was performed on the lung sections of 6 patients with rheumatoid arthritis-associated UIP (UIP-RA) and 6 patients with early-stage lung cancer as normal control.<BR><B>RESULTS: </B>The levels of serum HE4 and KL-6 were higher in patients with UIP-CTD than in healthy controls (292.3 pmol/L versus 79.5 pmol/L for HE4, p < 0.001; 1091.0 IU/mL versus 171.5 IU/mL for KL-6, p < 0.001). Significant correlations between serum HE4 levels and percentpredicted forced vital capacity (FVC%) (r = -0.425, p = 0.004), percent predicted diffusing capacity of the lung for carbon monoxide (DLCO%) (r = -0.447, p = 0.003), and Gender-Age-Physiology (GAP) index (r = 0.494, p < 0.001) were observed in UIP-CTD patients. In immunohistochemistry analysis, elevated expression of HE4 in bronchiolar epithelium and mesenchyme was observed in patients with UIP-RA compared with controls. The serum levels of HE4 (≥277.5 pmol/L) and GAP index were related to an increased risk of mortality (HR = 3.884, p = 0.034; HR = 1.480, p = 0.028, respectively).<BR><B>CONCLUSIONS: </B>The expression of HE4 in serum and lung specimens was significantly elevated in UIP-CTD patients. Moreover, serum HE4 may be utilized as a biomarker to evaluate the severity of disease and predict the prognosis of UIP-CTD patients.