{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,23]],"date-time":"2026-10-23T07:45:35Z","timestamp":1792741535084,"version":"4.5.0"},"reference-count":32,"publisher":"MDPI AG","issue":"2","license":[{"start":{"date-parts":[[2025,1,15]],"date-time":"2025-01-15T00:00:00Z","timestamp":1736899200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Tick-bite hypersensitivity encompasses a range of clinical manifestations, from localized allergic reactions to systemic conditions like alpha-gal syndrome (AGS), an IgE-mediated allergy to galactose-\u03b1-1,3-galactose (\u03b1-Gal). This study investigated the clinical, molecular, immunological, and genetic features of two hypersensitivity cases. Two cases were analyzed: a 30-year-old woman with fixed drug reaction (FDR)-like hypersensitivity and a 10-year-old girl with AGS exhibiting borderline \u03b1-Gal-specific IgE. Diagnostic methods included allergen-specific IgE quantification, HLA genotyping, histopathological examination, and the molecular detection of tick-borne pathogens using microfluidic PCR. Case I demonstrated histopathological features of chronic lymphocytic inflammation and eosinophilic infiltrates, with HLA-B13 and DRB113 alleles indicating genetic susceptibility to hypersensitivity, while histological findings suggested a localized FDR-like reaction. Case II exhibited borderline \u03b1-Gal-specific IgE, resolving completely with a mammalian-free diet. The presence of HLA-DRB101 and DQB1*05 in the second patient indicated a genetic predisposition to AGS and other atopic conditions. No infectious etiology was identified in either case. These findings emphasize the heterogeneity of tick-related hypersensitivity and the importance of HLA genotypes in susceptibility. Comprehensive molecular, immunological, and genetic profiling offers valuable insights into the mechanisms of hypersensitivity, supporting personalized approaches for the diagnosis and management of tick-induced allergic conditions.<\/jats:p>","DOI":"10.3390\/ijms26020680","type":"journal-article","created":{"date-parts":[[2025,1,15]],"date-time":"2025-01-15T05:59:42Z","timestamp":1736920782000},"page":"680","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Genetic and Immunological Insights into Tick-Bite Hypersensitivity and Alpha-Gal Syndrome: A Case Study Approach"],"prefix":"10.3390","volume":"26","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7902-6606","authenticated-orcid":false,"given":"Pavle","family":"Banovi\u0107","sequence":"first","affiliation":[{"name":"Clinic for Lyme Borreliosis and Other Tick-Borne Diseases, Department of Prevention of Rabies and Other Infectious Diseases, Pasteur Institute Novi Sad, 21000 Novi Sad, Serbia"},{"name":"Department of Microbiology with Parasitology and Immunology, Faculty of Medicine in Novi Sad, University of Novi Sad, 21000 Novi Sad, Serbia"},{"name":"Diagnostics and Laboratory Research Task Force, Balkan Association for Vector-Borne Diseases, 21000 Novi Sad, Serbia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2178-7223","authenticated-orcid":false,"given":"Dejan","family":"Jakimovski","sequence":"additional","affiliation":[{"name":"Faculty of Medicine, Ss. Cyril and Methodius University in Skopje, 1000 Skopje, North Macedonia"},{"name":"University Clinic for Infectious Diseases and Febrile Conditions, 1000 Skopje, North Macedonia"},{"name":"Clinical medicine Task Force, Balkan Association for Vector-Borne Diseases, 21000 Novi Sad, Serbia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4970-0748","authenticated-orcid":false,"given":"Dragana","family":"Mijatovi\u0107","sequence":"additional","affiliation":[{"name":"Diagnostics and Laboratory Research Task Force, Balkan Association for Vector-Borne Diseases, 21000 Novi Sad, Serbia"},{"name":"Department for Research & Monitoring of Rabies & Other Zoonoses, Pasteur Institute Novi Sad, 21000 Novi Sad, Serbia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3830-1947","authenticated-orcid":false,"given":"Ivana","family":"Bogdan","sequence":"additional","affiliation":[{"name":"Diagnostics and Laboratory Research Task Force, Balkan Association for Vector-Borne Diseases, 21000 Novi Sad, Serbia"},{"name":"Department of Microbiology, Pasteur Institute Novi Sad, 21000 Novi Sad, Serbia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Verica","family":"Simin","sequence":"additional","affiliation":[{"name":"Diagnostics and Laboratory Research Task Force, Balkan Association for Vector-Borne Diseases, 21000 Novi Sad, Serbia"},{"name":"Department of Microbiology, Pasteur Institute Novi Sad, 21000 Novi Sad, Serbia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3092-4768","authenticated-orcid":false,"given":"Jasmina","family":"Gruji\u0107","sequence":"additional","affiliation":[{"name":"Diagnostics and Laboratory Research Task Force, Balkan Association for Vector-Borne Diseases, 21000 Novi Sad, Serbia"},{"name":"Department of Transfusiology, Faculty of Medicine in Novi Sad, University of Novi Sad, 21000 Novi Sad, Serbia"},{"name":"Blood Transfusion Institute of Vojvodina, 21000 Novi Sad, Serbia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Svetlana","family":"Vojvodi\u0107","sequence":"additional","affiliation":[{"name":"Department of Transfusiology, Faculty of Medicine in Novi Sad, University of Novi Sad, 21000 Novi Sad, Serbia"},{"name":"Blood Transfusion Institute of Vojvodina, 21000 Novi Sad, Serbia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8869-4806","authenticated-orcid":false,"given":"Nada","family":"Vu\u010dkovi\u0107","sequence":"additional","affiliation":[{"name":"Pathology and Histology Centre, Clinical Centre of Vojvodina, Novi Sad, Department of Pathology, Faculty of Medicine in Novi Sad, University of Novi Sad, 21000 Novi Sad, Serbia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2651-8468","authenticated-orcid":false,"given":"Kinga","family":"Lis","sequence":"additional","affiliation":[{"name":"Department of Allergology, Clinical Immunology and Internal Diseases, Collegium Medicum in Bydgoszcz, Nicolaus Copernicus University in Toru\u0144, Ujejskiego 75, 85-168 Bydgoszcz, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2862-7182","authenticated-orcid":false,"given":"Eleftherios","family":"Meletis","sequence":"additional","affiliation":[{"name":"Faculty of Public and One Health, University of Thessaly, 43100 Karditsa, Greece"},{"name":"Epidemiology and Biostatistics Research Task Force, Balkan Association for Vector-Borne Diseases, 21000 Novi Sad, Serbia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7051-1541","authenticated-orcid":false,"given":"Polychronis","family":"Kostoulas","sequence":"additional","affiliation":[{"name":"Faculty of Public and One Health, University of Thessaly, 43100 Karditsa, Greece"},{"name":"Epidemiology and Biostatistics Research Task Force, Balkan Association for Vector-Borne Diseases, 21000 Novi Sad, Serbia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0008-4221-0301","authenticated-orcid":false,"given":"Marija","family":"Cvetkova Mladenovska","sequence":"additional","affiliation":[{"name":"Orthopedic Surgery, Anesthesiology and Intensive Care and Emergency Center, University Clinic for Traumatology, 1000 Skopje, North 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France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8660-730X","authenticated-orcid":false,"given":"Alejandro","family":"Cabezas-Cruz","sequence":"additional","affiliation":[{"name":"Agence Nationale de S\u00e9curit\u00e9 Sanitaire de l\u2019alimentation, de l\u2019environnement et du Travail, l\u2019Institut National de Recherche Pour l\u2019agriculture, l\u2019alimentation et l\u2019environnement, Ecole Nationale V\u00e9t\u00e9rinaire d\u2019Alfort, UMR Biologie Mol\u00e9culaire et Immunologie Parasitaires, Laboratoire de Sant\u00e9 Animale, F-94700 Maisons-Alfort, France"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,1,15]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1061","DOI":"10.1016\/j.jaci.2020.01.047","article-title":"On the Cause and Consequences of IgE to Galactose-\u03b1-1,3-Galactose: A Report from the National Institute of 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