Human epididymis protein 4 (HE4) is a novel biomarker for fibrosis in IgG4-related disease and can predict poor prognosis
Wen Zhang,
Yongzhe Li,
Yuan Huang,
Songxin Yan,
Yu Peng,
Hui Lu,
Ziyan Wu,
Shengwei Mo,
Xianlong Chen,
Xiaomeng Li
Affiliations
Wen Zhang
Department of Rheumatology and Clinical Immunology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, Peking Union Medical College, Beijing, China
Yongzhe Li
Department of Clinical Laboratory, State Key Laboratory of Complex Severe and Rare Diseases, Peking Union Medical College Hospital, Chinese Academy of Medical Science and Peking Union Medical College, Dongcheng District, Beijing, China
Yuan Huang
Health Services Research & Development, VA Connecticut Healthcare System, West Haven, Connecticut, USA
Songxin Yan
Department of Clinical Laboratory, State Key Laboratory of Complex Severe and Rare Diseases, Peking Union Medical College Hospital, Chinese Academy of Medical Science and Peking Union Medical College, Dongcheng District, Beijing, China
Yu Peng
Department of Rheumatology, State Key Laboratory of Complex Severe and Rare Diseases, National Clinical Research Center for Dermatologic and Immunologic Diseases, Peking Union Medical College Hospital, Chinese Academy of Medical Science and Peking Union Medical College, Dongcheng District, Beijing, China
Hui Lu
Department of Rheumatology, State Key Laboratory of Complex Severe and Rare Diseases, National Clinical Research Center for Dermatologic and Immunologic Diseases, Peking Union Medical College Hospital, Chinese Academy of Medical Science and Peking Union Medical College, Dongcheng District, Beijing, China
Ziyan Wu
Department of Clinical Laboratory, State Key Laboratory of Complex Severe and Rare Diseases, Peking Union Medical College Hospital, Chinese Academy of Medical Science and Peking Union Medical College, Dongcheng District, Beijing, China
Shengwei Mo
Department of Pathology, State Key Laboratory of Complex Severe and Rare Diseases, Peking Union Medical College Hospital, Chinese Academy of Medical Science and Peking Union Medical College, Dongcheng District, Beijing, China
Xianlong Chen
Department of Pathology, State Key Laboratory of Complex Severe and Rare Diseases, Peking Union Medical College Hospital, Chinese Academy of Medical Science and Peking Union Medical College, Dongcheng District, Beijing, China
Xiaomeng Li
Department of Clinical Laboratory, State Key Laboratory of Complex Severe and Rare Diseases, Peking Union Medical College Hospital, Chinese Academy of Medical Science and Peking Union Medical College, Dongcheng District, Beijing, China
Objectives IgG4-related disease (IgG4-RD) is an immune-mediated fibroinflammatory disorder with heterogeneous manifestations. This study aimed to investigate the utility of human epididymis protein 4 (HE4) as a potential clinical biomarker of fibrosis in IgG4-RD.Methods Plasma HE4 levels were estimated in 136 patients with IgG4-RD and 73 healthy individuals (controls) by electrochemical luminescence. HE4 expression levels and the degree of fibrosis in pancreatic tissues from 15 patients with IgG4-RD and 10 controls were compared using immunohistochemistry and Masson trichrome staining. Correlation between HE4 levels and laboratory parameters was determined, and the efficacy of HE4 as a biomarker of fibrosis and prognosis in IgG4-RD was also evaluated.Results Plasma HE4 levels were significantly higher in patients with IgG4-RD compared with controls. Optimal HE4 cut-off value for identifying patients with IgG4-RD was determined to be 50.8 pmol/L with an AUC (area under curve) of 0.791. HE4 levels were positively correlated with diverse laboratory parameters, and indicators of organ function impairment. Additionally, HE4 was highly expressed in the affected organs in patients with IgG4-RD and its plasma levels were closely correlated with degree of fibrosis, indicating the utility of HE4 in assessing internal organ damage and fibrosis. Further analysis showed that patients in the HE4 high expression group had poor prognosis.Conclusions Our results demonstrate that HE4 can be used as a biomarker for IgG4-RD as it is correlated with diverse baseline clinical features, internal organ damage and degree of fibrosis in affected organs, and can predict poor prognosis.
