{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,16]],"date-time":"2026-07-16T12:21:58Z","timestamp":1784204518810,"version":"3.55.0"},"reference-count":48,"publisher":"MDPI AG","issue":"18","license":[{"start":{"date-parts":[[2025,9,11]],"date-time":"2025-09-11T00:00:00Z","timestamp":1757548800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Ministry of Science, Technological Development and Innovation, Republic of Serbia","award":["451-03-68\/2020-14\/200110"],"award-info":[{"award-number":["451-03-68\/2020-14\/200110"]}]},{"name":"Ministry of Science, Technological Development and Innovation, Republic of Serbia","award":["175065"],"award-info":[{"award-number":["175065"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Diagnostics"],"abstract":"<jats:p>Background\/Objectives: Binding of bactericidal\/permeability-increasing (BPI) protein to Gram-negative (GN) bacteria plays a major role in bacterial elimination. The relationship between BPI-antineutrophil cytoplasmic autoantibodies (ANCA), persistent infections and immunoinflammatory diseases has not been elucidated. Methods: In total, 193 ANCA-positive patients detected by IIF with ANCA-associated vasculitides (AAV, n-40), connective tissue diseases (CTD, n-28), drug-induced vasculitides (DIV, n-17), ulcerative colitis (UC, n-24), UC with primary sclerosing cholangitis (UC\/PSC, n-14), Crohn\u2019s disease (CD, n-10), autoimmune hepatitis (AIH, n-19) and chronic infections (n-41) were tested using the BPI-ANCA quantitative and semiquantitative ELISA (ANCA-profile: BPI, proteinase 3, myeloperoxidase, elastase, cathepsin G, lactoferrin). BPI-ANCA were analyzed in 52 healthy persons. Results: A total of 46\/193 (23.8%) patients had BPI-ANCA positivity. BPI-ANCA were more frequently present in patients with prolonged GN bacterial infections and inflammatory bowel diseases than in AAV, DIV, AIH, CTD and healthy controls (p &lt; 0.001). UC\/PSC patients more frequently had BPI-ANCA than UC and CD patients (p &lt; 0.001). GN bacterial infections more frequently had BPI-ANCA than Gram-positive bacterial infections (p &lt; 0.001). Infections caused by Pseudomonas aeruginosa and Mycobacterium tuberculosis had monospecific BPI-ANCA (sensitivity 79% and 71%, respectively). UC\/PSC and chronic GN bacterial infections caused by Klebsiella pneumoniae, Proteus mirabilis, or Escherichia coli had multispecific BPI-ANCA (sensitivity 64% and 100%, respectively). Odds ratio analysis showed that patients with IBD who were positive for multispecific BPI-ANCA had a 13.5-fold increased risk of UC\/PSC (95% CI 2.98\u201361.18). Conclusions: Monospecific BPI-ANCA may be a valuable biomarker for persistent Pseudomonas aeruginosa and Mycobacterium tuberculosis infections. In contrast, multispecific BPI-ANCA are associated with UC\/PSC and persistent infections caused by intestinal Gram-negative bacteria. Suppression of antimicrobial function by multispecific BPI-ANCA could impair the elimination of Gram-negative bacteria, sustaining the immunoinflammation. Dysregulated antimicrobial response might be the target of immunomodulatory therapy in the initial phase of BPI-ANCA-positive UC\/PSC.<\/jats:p>","DOI":"10.3390\/diagnostics15182309","type":"journal-article","created":{"date-parts":[[2025,9,11]],"date-time":"2025-09-11T10:50:04Z","timestamp":1757587804000},"page":"2309","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Antineutrophil Cytoplasmic Autoantibodies Specific to Bactericidal\/Permeability-Increasing Protein: A Cross-Road Between Prolonged Gram-Negative Bacterial Infections and Ulcerative Colitis\/Primary Sclerosing Cholangitis"],"prefix":"10.3390","volume":"15","author":[{"given":"Dragana","family":"Jovanovic","sequence":"first","affiliation":[{"name":"Clinic of Allergy and Immunology, University Clinical Center of Serbia, 11000 Belgrade, Serbia"},{"name":"Faculty of Medicine, University of Belgrade, 11000 Belgrade, Serbia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0982-2572","authenticated-orcid":false,"given":"Rada","family":"Miskovic","sequence":"additional","affiliation":[{"name":"Clinic of Allergy and Immunology, University Clinical Center of Serbia, 11000 Belgrade, Serbia"},{"name":"Faculty of Medicine, University of Belgrade, 11000 Belgrade, Serbia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aleksandra","family":"Plavsic","sequence":"additional","affiliation":[{"name":"Clinic of Allergy and Immunology, University Clinical Center of Serbia, 11000 Belgrade, Serbia"},{"name":"Faculty of Medicine, University of Belgrade, 11000 Belgrade, Serbia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0003-1508-178X","authenticated-orcid":false,"given":"Sara","family":"Radovic","sequence":"additional","affiliation":[{"name":"Clinic of Allergy and Immunology, University Clinical Center of Serbia, 11000 Belgrade, Serbia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ljudmila","family":"Nagorni-Obradovic","sequence":"additional","affiliation":[{"name":"Faculty of Medicine, University of Belgrade, 11000 Belgrade, Serbia"},{"name":"Clinic of Pulmonology, University Clinical Center of Serbia, 11000 Belgrade, Serbia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dragan","family":"Popovic","sequence":"additional","affiliation":[{"name":"Faculty of Medicine, University of Belgrade, 11000 Belgrade, Serbia"},{"name":"Clinic of Gastroenterohepatology, University Clinical Center of Serbia, 11000 Belgrade, Serbia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3926-5394","authenticated-orcid":false,"given":"Milos M.","family":"Nikolic","sequence":"additional","affiliation":[{"name":"Faculty of Medicine, University of Belgrade, 11000 Belgrade, Serbia"},{"name":"Clinic of Dermatology and Venereology, University Clinical Center of Serbia, 11000 Belgrade, Serbia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3014-4075","authenticated-orcid":false,"given":"Branka","family":"Bonaci-Nikolic","sequence":"additional","affiliation":[{"name":"Clinic of Allergy and Immunology, University Clinical Center of Serbia, 11000 Belgrade, Serbia"},{"name":"Faculty of Medicine, University of Belgrade, 11000 Belgrade, Serbia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,9,11]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"100105","DOI":"10.1016\/j.jtauto.2021.100105","article-title":"Killing three birds with one BPI: Bactericidal, opsonic, and anti-inflammatory functions","volume":"28","author":"Theprungsirikul","year":"2021","journal-title":"J. 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