{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,2]],"date-time":"2026-04-02T05:39:44Z","timestamp":1775108384566,"version":"3.50.1"},"reference-count":22,"publisher":"MDPI AG","issue":"7","license":[{"start":{"date-parts":[[2026,3,31]],"date-time":"2026-03-31T00:00:00Z","timestamp":1774915200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100017950","name":"Shanghai Municipal Health Commission","doi-asserted-by":"crossref","award":["20234Y0110"],"award-info":[{"award-number":["20234Y0110"]}],"id":[{"id":"10.13039\/100017950","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Intestinal Beh\u00e7et\u2019s syndrome (BS) is a severe phenotype associated with high morbidity and mortality. Early identification of intestinal involvement in BS remains clinically challenging due to the lack of reliable biomarkers. Neutrophil gelatinase-associated lipocalin (NGAL) is abundantly secreted during intestinal inflammation and has been recognized as a promising inflammatory biomarker. This study was designed to investigate the clinical value of NGAL for predicting intestinal involvement in BS patients. BS patients who underwent colonoscopy for suspected intestinal lesions were enrolled and classified into intestinal BS and non-intestinal BS groups. Immunohistochemistry was performed to compare colonic mucosal NGAL expression among intestinal BS, non-intestinal BS, inflammatory bowel disease (IBD) patients, and healthy controls. Serum and fecal NGAL levels were also measured in intestinal BS, non-intestinal BS, and healthy controls. Intestinal mucosal NGAL expression was significantly elevated in both intestinal BS and IBD patients, with no significant difference between the two groups. Serum and fecal NGAL levels were both higher in intestinal BS patients than in healthy controls. Notably, only fecal NGAL was significantly increased in intestinal BS compared to non-intestinal BS (p &lt; 0.001). Multivariate logistic regression analysis identified fecal NGAL as an independent predictive factor for intestinal involvement in BS (OR = 1.093, 95% CI: 1.017\u20131.174, p = 0.015), with superior predictive performance over conventional inflammatory markers. In conclusion, fecal NGAL serves as a non-invasive and promising biomarker for risk stratification of intestinal involvement in BS patients. Further large-scale prospective studies are required to verify these preliminary results.<\/jats:p>","DOI":"10.3390\/ijms27073152","type":"journal-article","created":{"date-parts":[[2026,3,31]],"date-time":"2026-03-31T08:09:18Z","timestamp":1774944558000},"page":"3152","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Clinical Value of Neutrophil Gelatinase-Associated Lipocalin as a Non-Invasive Biomarker for Intestinal Ulcer in Beh\u00e7et\u2019s Syndrome: A Pilot Study"],"prefix":"10.3390","volume":"27","author":[{"given":"Jing-Fen","family":"Ye","sequence":"first","affiliation":[{"name":"Department of Rheumatology and Immunology, Huadong Hospital Affiliated to Fudan University, Shanghai 200040, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yi-Xuan","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Rheumatology and Immunology, Huadong Hospital Affiliated to Fudan University, Shanghai 200040, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Dan","family":"Hu","sequence":"additional","affiliation":[{"name":"Department of Rheumatology and Immunology, Huadong Hospital Affiliated to Fudan University, Shanghai 200040, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jian-Fei","family":"Cai","sequence":"additional","affiliation":[{"name":"Department of Rheumatology and Immunology, Huadong Hospital Affiliated to Fudan University, Shanghai 200040, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yu-Xin","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Rheumatology and Immunology, Huadong Hospital Affiliated to Fudan University, Shanghai 200040, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Li-Yang","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Rheumatology and Immunology, Huadong Hospital Affiliated to Fudan University, Shanghai 200040, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jun","family":"Zou","sequence":"additional","affiliation":[{"name":"Department of Rheumatology and Immunology, Huadong Hospital Affiliated to Fudan University, Shanghai 200040, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6481-480X","authenticated-orcid":false,"given":"Jian-Long","family":"Guan","sequence":"additional","affiliation":[{"name":"Department of Rheumatology and Immunology, Huadong Hospital Affiliated to Fudan University, Shanghai 200040, China"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2026,3,31]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"2261","DOI":"10.1007\/s10067-024-06995-4","article-title":"Clinical phenotypes of adult-onset Beh\u00e7et\u2019s syndrome: A comprehensive cross-sectional study in China","volume":"43","author":"She","year":"2024","journal-title":"Clin. Rheumatol."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"444","DOI":"10.1186\/s13023-021-02056-0","article-title":"New insight into the features of Beh\u00e7et\u2019s disease with gastrointestinal ulcer: A cross-sectional observational study","volume":"16","author":"Ye","year":"2021","journal-title":"Orphanet J. Rare Dis."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"57","DOI":"10.1016\/j.pathol.2024.07.005","article-title":"Intestinal vascular diseases misdiagnosed as Crohn disease: Analysis of 13 cases","volume":"57","author":"Chen","year":"2025","journal-title":"Pathology"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"679","DOI":"10.1007\/s00535-020-01690-y","article-title":"Evidence-based diagnosis and clinical practice guidelines for intestinal Beh\u00e7et\u2019s disease 2020 edited by Intractable Diseases, the Health and Labour Sciences Research Grants","volume":"55","author":"Watanabe","year":"2020","journal-title":"J. Gastroenterol."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"132","DOI":"10.1186\/s13023-021-01772-x","article-title":"Clinical characteristics and risk factors of intestinal involvement in Beh\u00e7et\u2019s syndrome patients: A cross-sectional study from a single center","volume":"16","author":"Hou","year":"2021","journal-title":"Orphanet J. Rare Dis."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"109318","DOI":"10.1016\/j.clim.2023.109318","article-title":"Neutrophil, NETs and Beh\u00e7et\u2019s disease: A review","volume":"250","author":"Cacoub","year":"2023","journal-title":"Clin. Immunol."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"149","DOI":"10.1080\/17520363.2025.2473312","article-title":"Novel inflammatory biomarkers for discriminating vascular involvement in Beh\u00e7et\u2019s syndrome: Evaluating SII, SIRI, and NPAR","volume":"19","author":"Ulusoy","year":"2025","journal-title":"Biomark. Med."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"206","DOI":"10.1007\/s00393-023-01412-8","article-title":"Role of neutrophil-to-lymphocyte ratio and platelet-to-lymphocyte ratio as potential biomarkers in Beh\u00e7et\u2019s disease: A meta-analysis","volume":"83","author":"Lee","year":"2023","journal-title":"Z. Rheumatol."},{"key":"ref_9","doi-asserted-by":"crossref","unstructured":"Araos, P., and Amador, C.A. (2022). Neutrophil gelatinase-associated lipocalin as an immunomodulator in endocrine hypertension. Front. Endocrinol., 13.","DOI":"10.3389\/fendo.2022.1006790"},{"key":"ref_10","doi-asserted-by":"crossref","unstructured":"Romejko, K., Markowska, M., and Niemczyk, S. (2023). The Review of Current Knowledge on Neutrophil Gelatinase-Associated Lipocalin (NGAL). Int. J. Mol. Sci., 24.","DOI":"10.3390\/ijms241310470"},{"key":"ref_11","doi-asserted-by":"crossref","unstructured":"Baker, T.M., Bird, C.A., Broyles, D.L., and Klause, U. (2025). Determination of Urinary Neutrophil Gelatinase-Associated Lipocalin (uNGAL) Reference Intervals in Healthy Adult and Pediatric Individuals Using a Particle-Enhanced Turbidimetric Immunoassay. Diagnostics, 15.","DOI":"10.3390\/diagnostics15010095"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"43","DOI":"10.1093\/ecco-jcc\/jjaa124","article-title":"Faecal Biomarkers in Inflammatory Bowel Diseases: Calprotectin Versus Lipocalin-2\u2014A Comparative Study","volume":"15","author":"Zollner","year":"2020","journal-title":"J. Crohn\u2019s Colitis"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"914","DOI":"10.1007\/s00535-021-01814-y","article-title":"Mucosal and faecal neutrophil gelatinase-associated lipocalin as potential biomarkers for collagenous colitis","volume":"56","author":"Bakke","year":"2021","journal-title":"J. Gastroenterol."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"1493","DOI":"10.4240\/wjgs.v16.i6.1493","article-title":"Intestinal Beh\u00e7et\u2019s disease: A review of clinical diagnosis and treatment","volume":"16","author":"Liu","year":"2024","journal-title":"World J. Gastrointest. Surg."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"388","DOI":"10.1016\/j.tem.2017.01.003","article-title":"Lipocalin-2: A Master Mediator of Intestinal and Metabolic Inflammation","volume":"28","author":"Moschen","year":"2017","journal-title":"Trends Endocrinol. Metab."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"502","DOI":"10.1111\/cei.12136","article-title":"Expression of Toll-like receptor-3 is enhanced in active inflammatory bowel disease and mediates the excessive release of lipocalin 2","volume":"173","author":"Granlund","year":"2013","journal-title":"Clin. Exp. Immunol."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"339","DOI":"10.1007\/s00441-018-2860-8","article-title":"Expression of neutrophil gelatinase-associated lipocalin (NGAL) in the gut in Crohn\u2019s disease","volume":"374","author":"Thorsvik","year":"2018","journal-title":"Cell Tissue Res."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"128","DOI":"10.1111\/jgh.13598","article-title":"Fecal neutrophil gelatinase-associated lipocalin as a biomarker for inflammatory bowel disease","volume":"32","author":"Thorsvik","year":"2017","journal-title":"J. Gastroenterol. Hepatol."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"3321","DOI":"10.1007\/s10792-022-02331-4","article-title":"Interleukin 18, soluble cluster of differentiation 40, platelet factor 4 variant 1, and neutrophil gelatinase-associated lipocalin can be used as biomarkers to aid activity and diagnosis in ocular Beh\u00e7et\u2019s disease","volume":"42","author":"Celik","year":"2022","journal-title":"Int. Ophthalmol."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"195","DOI":"10.1684\/ejd.2014.2490","article-title":"Changes of serum lipocalin-2 and retinol binding protein-4 levels in patients with psoriasis and Beh\u00e7et\u2019s disease","volume":"25","author":"Gul","year":"2015","journal-title":"Eur. J. Dermatol."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"51","DOI":"10.55133\/eji.330106","article-title":"Diagnostic value of serum lipocalin-2 in Egyptian patients with inflammatory bowel disease: A case-control study","volume":"33","author":"Fathi","year":"2026","journal-title":"Egypt. J. Immunol."},{"key":"ref_22","doi-asserted-by":"crossref","unstructured":"Yadav, S.K., Ito, N., Mindur, J.E., Kumar, H., Youssef, M., Suresh, S., Kulkarni, R., Rosario, Y., Balashov, K.E., and Dhib-Jalbut, S. (2022). Fecal Lcn-2 level is a sensitive biological indicator for gut dysbiosis and intestinal inflammation in multiple sclerosis. Front. Immunol., 13.","DOI":"10.3389\/fimmu.2022.1015372"}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/27\/7\/3152\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,4,2]],"date-time":"2026-04-02T04:13:42Z","timestamp":1775103222000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/27\/7\/3152"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,3,31]]},"references-count":22,"journal-issue":{"issue":"7","published-online":{"date-parts":[[2026,4]]}},"alternative-id":["ijms27073152"],"URL":"https:\/\/doi.org\/10.3390\/ijms27073152","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,3,31]]}}}