REVIEW PAPER
HE4: a potential diagnostic biomarker in autoimmune diseases
1
Department of Laboratory Medicine, West China Second University Hospital, Sichuan University, Chengdu, 610041 Sichuan, PR China
2
Key Laboratory of Birth Defects and Related Diseases of Women and Children, Ministry of Education, Sichuan University, Chengdu, 610041 Sichuan, PR China
Submission date: 2025-01-22
Final revision date: 2025-05-20
Acceptance date: 2025-07-27
Online publication date: 2026-05-27
Corresponding author
Qinni Yang
Department of Laboratory Medicine, West China Second University Hospital, Sichuan University, Chengdu, 610041 Sichuan, PR China.
Department of Laboratory Medicine, West China Second University Hospital, Sichuan University, Chengdu, 610041 Sichuan, PR China.
KEYWORDS
ABSTRACT
Human epididymal protein 4 (HE4), also known as protein four-disulfide core domain 2, is a secretory protein that is highly expressed in epithelial ovarian cancer. HE4 has higher specificity and sensitivity than traditional biomarkers in ovarian cancer, making it an effective marker for monitoring the progression of ovarian cancer. Given the similarities between the pathological processes in cancer and autoimmune diseases (ADs), namely overactivation of immune cells and involvement of inflammatory responses, patients with ADs may have an increased risk of cancer. Accumulating evidence suggests that HE4 is strongly associated with ADs such as systemic lupus erythematosus, Sjögren’s syndrome, rheumatoid arthritis-associated interstitial lung disease, and immunoglobulin A nephropathy. Several studies have reported that HE4 reflects disease severity and has excellent potential as a biomarker for the diagnosis and progression monitoring of ADs. In this article, we provide a detailed overview of the research on the biological function of HE4 in ADs and provide insights into whether HE4 has the potential to serve as a candidate biomarker for chronic inflammatory ADs.
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