{"doi":"10.3389/fimmu.2024.1461987","title":"Increased serum human epididymis protein 4 is associated with disease activity and systemic involvement in pediatric-onset systemic lupus erythematosus","abstract":"<jats:sec><jats:title>Objective</jats:title><jats:p>We aimed to investigate human epididymis protein 4 (HE4) as a potential biomarker in patients with pediatric-onset systemic lupus erythematosus (pSLE), particularly on the association of serum HE4 levels with disease activity and other laboratory tests.</jats:p></jats:sec><jats:sec><jats:title>Methods</jats:title><jats:p>We included 137 patients with pSLE and 75 age- and sex-matched healthy controls (HCs). Serum HE4 level was measured by a chemiluminescent microparticle on an Abbott ARCHITECT i2000SR Immunoassay Analyzer. Comparisons between groups were performed using the independent Student t-test, Mann–Whitney U test, Chi-square test, or Fisher’s exact test, as appropriate. We also determined the relationships between HE4 and clinical parameters and evaluated disease activity using SLE Disease Activity Index (SLEDAI) and renal SLEDAI (rSLEDAI).</jats:p></jats:sec><jats:sec><jats:title>Results</jats:title><jats:p>Serum HE4 levels in patients with pSLE (44.6 pmol/L; IQR, 32.5–73.5) were significantly higher than those in HCs (38.9 pmol/L; IQR, 34–46.1). HE4 levels were significantly higher in moderate to severe disease activities (57.4 pmol/L, IQR 37.7–164.5) than in mild disease activities (38.8 pmol/L, IQR 30.1–48.5) or HCs (38.9 pmol/L, IQR 34.0–46.1), as well as in active renal disease activities (77.2 pmol/L, IQR 47.4–224.1) than in inactive renal disease activities (36.1 pmol/L, IQR 27.8–46.7). The ROC curve analysis showed that HE4 could discriminate pSLE with renal (AUC, 0.717; 95% CI, 0.632–0.801), hematological (AUC, 0.740; 95% CI, 0.648–0.831), and cardiovascular involvement (AUC:0.775, 95% CI 0.669–0.880). Serum HE4 levels significantly correlated with several indicators related to renal morbidity, such as creatinine, blood urea nitrogen, uric acid, cystatin C, urine protein/24 h, etc.</jats:p></jats:sec><jats:sec><jats:title>Conclusion</jats:title><jats:p>Serum HE4 levels in pSLE were elevated and highly associated with disease activity and systemic involvement, indicating HE4 as a potential biomarker for pSLE.</jats:p></jats:sec>","journal":"Frontiers in Immunology","year":2024,"id":679222,"datarank":0.24141568686511508,"base_score":1.6094379124341003,"endowment":1.6094379124341003,"self_citation_contribution":0.24141568686511508,"citation_network_contribution":0.0,"self_endowment_contribution":0.24141568686511508,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":4,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":null,"is_data_producer":false,"deposit_databanks":null,"is_oa":false,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":null,"fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":1774659,"name":"Lingyi Yan","orcid":null,"position":1,"is_corresponding":false},{"id":1774660,"name":"Menglan Zhang","orcid":null,"position":2,"is_corresponding":false},{"id":1081168,"name":"Yifei Duan","orcid":"0000-0001-8443-1606","position":3,"is_corresponding":false},{"id":1244909,"name":"Jie Luo","orcid":"0000-0003-1899-3111","position":4,"is_corresponding":false},{"id":228894,"name":"Zhijun Liu","orcid":"0000-0001-5533-3038","position":5,"is_corresponding":false},{"id":1362019,"name":"Ting Liu","orcid":"0009-0005-4487-2999","position":6,"is_corresponding":false},{"id":1774661,"name":"Jiyu Tong","orcid":null,"position":7,"is_corresponding":false},{"id":1583396,"name":"Yongmei Jiang","orcid":null,"position":8,"is_corresponding":false},{"id":241384,"name":"Chenxi Liu","orcid":"0000-0003-0142-553X","position":0,"is_corresponding":false}],"reference_count":0,"raw_metadata":{"has_enrichment":true,"resolved":true,"title":"Increased serum human epididymis protein 4 is associated with disease activity and systemic involvement in pediatric-onset systemic lupus erythematosus","abstract":"<jats:sec><jats:title>Objective</jats:title><jats:p>We aimed to investigate human epididymis protein 4 (HE4) as a potential biomarker in patients with pediatric-onset systemic lupus erythematosus (pSLE), particularly on the association of serum HE4 levels with disease activity and other laboratory tests.</jats:p></jats:sec><jats:sec><jats:title>Methods</jats:title><jats:p>We included 137 patients with pSLE and 75 age- and sex-matched healthy controls (HCs). Serum HE4 level was measured by a chemiluminescent microparticle on an Abbott ARCHITECT i2000SR Immunoassay Analyzer. Comparisons between groups were performed using the independent Student t-test, Mann–Whitney U test, Chi-square test, or Fisher’s exact test, as appropriate. We also determined the relationships between HE4 and clinical parameters and evaluated disease activity using SLE Disease Activity Index (SLEDAI) and renal SLEDAI (rSLEDAI).</jats:p></jats:sec><jats:sec><jats:title>Results</jats:title><jats:p>Serum HE4 levels in patients with pSLE (44.6 pmol/L; IQR, 32.5–73.5) were significantly higher than those in HCs (38.9 pmol/L; IQR, 34–46.1). HE4 levels were significantly higher in moderate to severe disease activities (57.4 pmol/L, IQR 37.7–164.5) than in mild disease activities (38.8 pmol/L, IQR 30.1–48.5) or HCs (38.9 pmol/L, IQR 34.0–46.1), as well as in active renal disease activities (77.2 pmol/L, IQR 47.4–224.1) than in inactive renal disease activities (36.1 pmol/L, IQR 27.8–46.7). The ROC curve analysis showed that HE4 could discriminate pSLE with renal (AUC, 0.717; 95% CI, 0.632–0.801), hematological (AUC, 0.740; 95% CI, 0.648–0.831), and cardiovascular involvement (AUC:0.775, 95% CI 0.669–0.880). Serum HE4 levels significantly correlated with several indicators related to renal morbidity, such as creatinine, blood urea nitrogen, uric acid, cystatin C, urine protein/24 h, etc.</jats:p></jats:sec><jats:sec><jats:title>Conclusion</jats:title><jats:p>Serum HE4 levels in pSLE were elevated and highly associated with disease activity and systemic involvement, indicating HE4 as a potential biomarker for pSLE.</jats:p></jats:sec>","is_dataset_classified":null,"base_score":1.6094379124341003,"endowment":1.6094379124341003,"datacite_reuse_total":0,"file_count":0,"downloads":0,"views":0,"has_version_chain":false,"is_dataset":false,"is_oa":false,"pmid":"39318632","pmcid":"PMC11419971","openalex_id":"https://openalex.org/W4402423033","authors":[],"funders":[],"total_grants":0,"fwci":0.8774,"citation_percentile":0.70383912,"influential_citations":0,"citation_trend":[{"year":2025,"count":3},{"year":2026,"count":1}],"oa_status":"gold","license":"cc-by","oa_locations":[{"url":"https://public-pages-files-2025.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2024.1461987/pdf","host_type":"journal"},{"url":"https://public-pages-files-2025.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2024.1461987/pdf","host_type":"publisher"},{"url":"https://www.frontiersin.org/articles/10.3389/fimmu.2024.1461987/full","host_type":"publisher"},{"url":"https://doi.org/10.3389/fimmu.2024.1461987","host_type":"journal"},{"url":"https://pubmed.ncbi.nlm.nih.gov/39318632","host_type":"repository"},{"url":"https://www.ncbi.nlm.nih.gov/pmc/articles/11419971","host_type":"repository"},{"url":"https://doaj.org/article/3cafcb9dfdcb4c3a9d8db1908a15e149","host_type":"repository"},{"url":"https://pmc.ncbi.nlm.nih.gov/articles/PMC11419971/pdf/fimmu-15-1461987.pdf","host_type":"repository"},{"url":"https://europepmc.org/articles/PMC11419971","host_type":"Europe_PMC"},{"url":"https://europepmc.org/articles/PMC11419971?pdf=render","host_type":"Europe_PMC"}],"fields_of_study":["Stress Responses and Cortisol","Hormonal and reproductive studies","Sperm and Testicular Function","Humans","WAP Four-Disulfide Core Domain Protein 2","Lupus Erythematosus, Systemic","Male","Female","Biomarkers","Child","Adolescent","Severity of Illness Index","Age of Onset","Case-Control Studies","ROC Curve"],"mesh_terms":["WAP Four-Disulfide Core Domain Protein 2","Adolescent","Child","Female","Humans","Lupus Erythematosus, Systemic","Male","ROC Curve","Severity of Illness Index","Biomarkers","Case-Control Studies","Age of Onset"],"keywords":["Systemic disease","Systemic lupus","Medicine","Epididymis","Immunology","Systemic therapy","Disease","Systemic inflammation","Systemic circulation","Internal medicine","Inflammation","Correlation","Biomarker","Lupus nephritis","Human Epididymis Protein 4","Pediatric-onset Systemic Lupus Erythematosus"],"sdg_mappings":[{"sdg_number":0,"sdg_label":"Good health and well-being"}],"linked_datasets":[],"clinical_trials":[],"software_tools":[],"database_accessions":[{"name":"doi"}],"source":"live","citation_network_status":"fetched"},"created_at":"2026-08-17T12:33:09.882366Z","pmid":null,"pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}