{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,13]],"date-time":"2026-09-13T17:50:52Z","timestamp":1789321852663,"version":"build-2803163510"},"reference-count":43,"publisher":"MDPI AG","issue":"13","license":[{"start":{"date-parts":[[2024,7,1]],"date-time":"2024-07-01T00:00:00Z","timestamp":1719792000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Diagnostics"],"abstract":"<jats:p>Upon first exposure to cetuximab, hypersensitivity reactions can occur. We aimed to assess the utility of the basophil activation test (BAT) to alpha-gal and cetuximab for predicting severe reactions. We prospectively recruited 38 patients and evaluated sIgE to alpha-gal in all patients before the first application of cetuximab. In all alpha-gal-sensitized patients, we evaluated skin tests to meat extracts, gelatine, and cetuximab and performed BAT with alpha-gal and cetuximab. In 24% (9\/38) of patients, sIgE to alpha-gal was &gt;0.10 kUA\/L, and 8\/9 reacted to the cetuximab. Basophil activation tests with alpha-gal were positive in all sensitized patients and were higher in those with severe reactions (18.3% in grade 4 [n = 4] vs. 1.8% in grade 2 [n = 3] or no reaction [n = 1] at 3.3 ng\/mL of alpha-gal; p = 0.03). All patients with severe grade 4 reactions had a positive CD63 BAT response to cetuximab compared to patients with moderate or no reaction, who all had negative BAT (57.7% vs. 0.9% at 500 \u00b5g\/mL, 63.2% vs. 4.1% at 100 \u00b5g\/mL, 58.2% vs. 2.7% at 10 \u00b5g\/mL, and 32.1% vs. 3.3% at 1 \u00b5g\/mL of cetuximab, respectively; p \u2264 0.001). In summary, before initiating cetuximab treatment, sIgE to alpha-gal should be assessed in all patients. To predict the severity of the reaction and to assess the risk of cetuximab-induced anaphylaxis, we should perform BATs with alpha-gal or more discriminative BATs with cetuximab.<\/jats:p>","DOI":"10.3390\/diagnostics14131403","type":"journal-article","created":{"date-parts":[[2024,7,1]],"date-time":"2024-07-01T08:17:29Z","timestamp":1719821849000},"page":"1403","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":12,"title":["Basophil Activation Test Predicts Cetuximab Anaphylaxis Severity in Alpha-Gal IgE-Positive Patients"],"prefix":"10.3390","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7261-6689","authenticated-orcid":false,"given":"Peter","family":"Kopa\u010d","sequence":"first","affiliation":[{"name":"University Clinic of Respiratory and Allergic Diseases Golnik, 4204 Golnik, Slovenia"},{"name":"Medical Faculty, University of Ljubljana, 1000 Ljubljana, Slovenia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9671-1645","authenticated-orcid":false,"given":"Ana","family":"Koren","sequence":"additional","affiliation":[{"name":"University Clinic of Respiratory and Allergic Diseases Golnik, 4204 Golnik, Slovenia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8978-6887","authenticated-orcid":false,"given":"Ur\u0161ka","family":"Bidovec-Stojkovi\u010d","sequence":"additional","affiliation":[{"name":"University Clinic of Respiratory and Allergic Diseases Golnik, 4204 Golnik, Slovenia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4701-7374","authenticated-orcid":false,"given":"Mitja","family":"Ko\u0161nik","sequence":"additional","affiliation":[{"name":"University Clinic of Respiratory and Allergic Diseases Golnik, 4204 Golnik, Slovenia"},{"name":"Medical Faculty, University of Ljubljana, 1000 Ljubljana, Slovenia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0002-1973-1869","authenticated-orcid":false,"given":"Luka","family":"Dejanovi\u0107","sequence":"additional","affiliation":[{"name":"University Clinic of Respiratory and Allergic Diseases Golnik, 4204 Golnik, Slovenia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6129-532X","authenticated-orcid":false,"given":"Tanja","family":"Mesti","sequence":"additional","affiliation":[{"name":"Medical Faculty, University of Ljubljana, 1000 Ljubljana, Slovenia"},{"name":"Institute of Oncology, 1000 Ljubljana, Slovenia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0445-112X","authenticated-orcid":false,"given":"Primo\u017e","family":"Strojan","sequence":"additional","affiliation":[{"name":"Medical Faculty, University of Ljubljana, 1000 Ljubljana, Slovenia"},{"name":"Institute of Oncology, 1000 Ljubljana, Slovenia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter","family":"Koro\u0161ec","sequence":"additional","affiliation":[{"name":"University Clinic of Respiratory and Allergic Diseases Golnik, 4204 Golnik, Slovenia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Janja","family":"Ocvirk","sequence":"additional","affiliation":[{"name":"Medical Faculty, University of Ljubljana, 1000 Ljubljana, Slovenia"},{"name":"Institute of Oncology, 1000 Ljubljana, Slovenia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,7,1]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"97","DOI":"10.1007\/s40629-020-00126-6","article-title":"Hypersensitivity Reactions to Biologics (Part I): Allergy as an Important Differential Diagnosis in Complex Immune-Derived Adverse Events","volume":"29","author":"Wedi","year":"2020","journal-title":"Allergo J. Int."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"175","DOI":"10.1016\/j.jaip.2014.12.006","article-title":"Hypersensitivity to Biological Agents-Updated Diagnosis, Management, and Treatment","volume":"3","author":"Castells","year":"2015","journal-title":"J. Allergy Clin. Immunol. Pract."},{"key":"ref_3","doi-asserted-by":"crossref","unstructured":"Castells, M. (2017). Drug Hypersensitivity and Anaphylaxis in Cancer and Chronic Inflammatory Diseases: The Role of Desensitizations. Front. Immunol., 8.","DOI":"10.3389\/fimmu.2017.01472"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"39","DOI":"10.1111\/all.14984","article-title":"Hypersensitivity Reactions to Biologicals: An EAACI Position Paper","volume":"77","author":"Bavbek","year":"2022","journal-title":"Allergy"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"139","DOI":"10.1007\/s40629-020-00127-5","article-title":"Hypersensitivity Reactions to Biologics (Part II): Classifications and Current Diagnostic and Treatment Approaches","volume":"29","author":"Wedi","year":"2020","journal-title":"Allergo J. Int."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"55","DOI":"10.1586\/eci.10.90","article-title":"Acute Infusion Reactions Induced by Monoclonal Antibody Therapy","volume":"7","author":"Maggi","year":"2011","journal-title":"Expert Rev. Clin. Immunol."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"600","DOI":"10.1016\/j.jaip.2016.12.001","article-title":"Current Knowledge and Management of Hypersensitivity Reactions to Monoclonal Antibodies","volume":"5","author":"Picard","year":"2017","journal-title":"J. Allergy Clin. Immunol. Pract."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"396","DOI":"10.4161\/mabs.3.4.16293","article-title":"Anti-Cetuximab IgE ELISA for Identification of Patients at a High Risk of Cetuximab-Induced Anaphylaxis","volume":"3","author":"Mariotte","year":"2011","journal-title":"mAbs"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"5","DOI":"10.1186\/1476-7961-10-5","article-title":"Anaphylactic Reactions to Oligosaccharides in Red Meat: A Syndrome in Evolution","volume":"10","author":"Saleh","year":"2012","journal-title":"Clin. Mol. Allergy"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"21355","DOI":"10.1038\/s41598-020-78497-7","article-title":"The Role of IgE Specific for Galactose-\u03b1-1,3-Galactose in Predicting Cetuximab Induced Hypersensitivity Reaction: A Systematic Review and a Diagnostic Meta-Analysis","volume":"10","author":"Lungulescu","year":"2020","journal-title":"Sci. Rep."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"2133","DOI":"10.2217\/fon.14.153","article-title":"Risk Factors Associated with Hypersensitivity Reactions to Cetuximab: Anti-Cetuximab IgE Detection as Screening Test","volume":"10","author":"Dupont","year":"2014","journal-title":"Future Oncol."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"693","DOI":"10.1038\/nm.2755","article-title":"IgE and Mast Cells in Allergic Disease","volume":"18","author":"Galli","year":"2012","journal-title":"Nat. Med."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"265","DOI":"10.1111\/all.12317","article-title":"Serum Basal Tryptase May Be a Good Marker for Predicting the Risk of Anaphylaxis in Children with Food Allergy","volume":"69","author":"Sahiner","year":"2014","journal-title":"Allergy Eur. J. Allergy Clin. Immunol."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"180","DOI":"10.2500\/aap.2019.40.4211","article-title":"Factors Predicting Anaphylaxis in Children with Tree Nut Allergies","volume":"40","author":"Cetinkaya","year":"2019","journal-title":"Allergy Asthma Proc."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"1047","DOI":"10.1016\/j.jaci.2009.08.027","article-title":"Predictors of Severe Systemic Anaphylactic Reactions in Patients with Hymenoptera Venom Allergy: Importance of Baseline Serum Tryptase\u2014A Study of the European Academy of Allergology and Clinical Immunology Interest Group on Insect Venom Hypersensitivity","volume":"124","author":"Przybilla","year":"2009","journal-title":"J. Allergy Clin. Immunol."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"105","DOI":"10.1016\/j.jaci.2010.04.025","article-title":"Predictors of Side Effects during the Buildup Phase of Venom Immunotherapy for Hymenoptera Venom Allergy: The Importance of Baseline Serum Tryptase","volume":"126","author":"Przybilla","year":"2010","journal-title":"J. Allergy Clin. Immunol."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"3157","DOI":"10.1016\/j.jaip.2021.04.045","article-title":"Biomarkers of the Severity of Honeybee Sting Reactions and the Severity and Threshold of Systemic Adverse Events During Immunotherapy","volume":"9","author":"Custovic","year":"2021","journal-title":"J. Allergy Clin. Immunol. Pract."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"182","DOI":"10.1016\/j.jaci.2018.06.049","article-title":"The Basophil Activation Test Differentiates between Patients with Alpha-Gal Syndrome and Asymptomatic Alpha-Gal Sensitization","volume":"143","author":"Mehlich","year":"2019","journal-title":"J. Allergy Clin. Immunol."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"1393","DOI":"10.1111\/all.12698","article-title":"The Clinical Utility of Basophil Activation Testing in Diagnosis and Monitoring of Allergic Disease","volume":"70","author":"Hoffmann","year":"2015","journal-title":"Allergy"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"344","DOI":"10.1016\/j.jaci.2020.03.035","article-title":"Biomarkers of Severity and Threshold of Allergic Reactions during Oral Peanut Challenges","volume":"146","author":"Santos","year":"2020","journal-title":"J. Allergy Clin. Immunol."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"179","DOI":"10.1016\/j.jaci.2014.09.001","article-title":"Distinct Parameters of the Basophil Activation Test Reflect the Severity and Threshold of Allergic Reactions to Peanut","volume":"135","author":"Santos","year":"2015","journal-title":"J. Allergy Clin. Immunol."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"1579","DOI":"10.1111\/cea.12582","article-title":"Immunological and Clinical Factors Associated with Adverse Systemic Reactions during the Build-up Phase of Honeybee Venom Immunotherapy","volume":"45","author":"Rijavec","year":"2015","journal-title":"Clin. Exp. Allergy"},{"key":"ref_23","first-page":"263","article-title":"Unsuccessful Desensitization to Paclitaxel in a Patient with High Basophil Sensitivity","volume":"31","author":"Koren","year":"2020","journal-title":"J. Investig. Allergol. Clin. Immunol."},{"key":"ref_24","doi-asserted-by":"crossref","unstructured":"La Sorda, M., Fossati, M., Graffeo, R., Ferraironi, M., De Rosa, M.C., Buzzonetti, A., Righino, B., Zampetti, N., Fattorossi, A., and Nucera, E. (2023). A Modified Basophil Activation Test for the Clinical Management of Immediate Hypersensitivity Reactions to Paclitaxel: A Proof-of-Concept Study. Cancers, 15.","DOI":"10.3390\/cancers15245818"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"e1265","DOI":"10.1002\/iid3.1265","article-title":"Basophil Allergen Threshold Sensitivity to Casein (Casein-specific CD-sens) Predicts Allergic Reactions at a Milk Challenge in Most but Not All Patients","volume":"12","author":"Nopp","year":"2024","journal-title":"Immun. Inflamm. Dis."},{"key":"ref_26","unstructured":"National Cancer Institute (2017). Common Terminology Criteria for Adverse Events (CTCAE) v5.0, National Cancer Institute."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"1730","DOI":"10.1111\/j.1365-2222.2009.03347.x","article-title":"Basophil Responsiveness in Patients with Insect Sting Allergies and Negative Venom-Specific Immunoglobulin E and Skin Prick Test Results","volume":"39","author":"Korosec","year":"2009","journal-title":"Clin. Exp. Allergy"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"1753","DOI":"10.1111\/all.14185","article-title":"Fluorescent Labeling of Major Honeybee Allergens Api m 1 and Api m 2 with Quantum Dots and the Development of a Multiplex Basophil Activation Test","volume":"75","author":"Koren","year":"2020","journal-title":"Allergy"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"92","DOI":"10.1111\/j.1398-9995.2010.02432.x","article-title":"Benefit of the Basophil Activation Test in Deciding When to Reintroduce Cow\u2019s Milk in Allergic Children","volume":"66","author":"Rubio","year":"2011","journal-title":"Allergy"},{"key":"ref_30","first-page":"212","article-title":"Hypersensitivity Reactions to Biological Drugs","volume":"24","author":"Corominas","year":"2014","journal-title":"J. Investig. Allergol. Clin. Immunol."},{"key":"ref_31","doi-asserted-by":"crossref","unstructured":"Serrier, J., Davy, J.-B., Dupont, B., Clarisse, B., Parienti, J.-J., Petit, G., Khoy, K., Ollivier, Y., Gervais, R., and Mariotte, D. (2023). Validation of an Anti-\u03b1-Gal IgE Fluoroenzyme-Immunoassay for the Screening of Patients at Risk of Severe Anaphylaxis to Cetuximab. BMC Cancer, 23.","DOI":"10.1186\/s12885-023-10501-5"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"1540","DOI":"10.1111\/all.13156","article-title":"Prevalence of Type I Sensitization to Alpha-Gal in Forest Service Employees and Hunters","volume":"72","author":"Fischer","year":"2017","journal-title":"Allergy"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"377","DOI":"10.1111\/cea.12655","article-title":"High Prevalence of SIgE to Galactose-\u03b1-1,3-Galactose in Rural Pre-Alps Area: A Cross-Sectional Study","volume":"46","author":"Villalta","year":"2016","journal-title":"Clin. Exp. Allergy"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"430","DOI":"10.12998\/wjcc.v3.i5.430","article-title":"Tick-Borne Encephalitis: A Review of Epidemiology, Clinical Characteristics, and Management","volume":"3","author":"Bogovic","year":"2015","journal-title":"World J. Clin. Cases"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"156","DOI":"10.1089\/vbz.2022.0071","article-title":"Incidence of Lyme Borreliosis in Europe from National Surveillance Systems (2005\u20132020)","volume":"23","author":"Burn","year":"2023","journal-title":"Vector Borne Zoonotic Dis."},{"key":"ref_36","first-page":"2200543","article-title":"Spatiotemporal Spread of Tick-Borne Encephalitis in the EU\/EEA, 2012 to 2020","volume":"28","author":"Haussig","year":"2023","journal-title":"Euro Surveill."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"197","DOI":"10.1111\/cea.14054","article-title":"Delayed Reaction in Alpha-Gal Allergy Is Reflected in Serum Levels after Ingestion of Pork Kidney, and Absorption Is Dependent on Food Processing","volume":"52","author":"Eller","year":"2022","journal-title":"Clin. Exp. Allergy"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"574","DOI":"10.1038\/nbt.1912","article-title":"Anti-Galactose-\u03b1-1,3-Galactose IgE from Allergic Patients Does Not Bind \u03b1-Galactosylated Glycans on Intact Therapeutic Antibody Fc Domains","volume":"29","author":"Rispens","year":"2011","journal-title":"Nat. Biotechnol."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"350","DOI":"10.1111\/cea.13307","article-title":"The Basophil Activation Test Reduces the Need for a Food Challenge Test in Children Suspected of IgE-Mediated Cow\u2019s Milk Allergy","volume":"49","author":"Jansen","year":"2019","journal-title":"Clin. Exp. Allergy"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"645","DOI":"10.1016\/j.jaci.2014.04.039","article-title":"Basophil Activation Test Discriminates between Allergy and Tolerance in Peanut-Sensitized Children","volume":"134","author":"Santos","year":"2014","journal-title":"J. Allergy Clin. Immunol."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"1322","DOI":"10.1111\/all.13380","article-title":"Factors Increasing the Risk for a Severe Reaction in Anaphylaxis: An Analysis of Data from The European Anaphylaxis Registry","volume":"73","author":"Worm","year":"2018","journal-title":"Allergy Eur. J. Allergy Clin. Immunol."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"653","DOI":"10.1016\/j.jaci.2020.06.008","article-title":"Phenotype and Risk Factors of Venom-Induced Anaphylaxis: A Case-Control Study of the European Anaphylaxis Registry","volume":"147","author":"Francuzik","year":"2020","journal-title":"J. Allergy Clin. Immunol."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"1061","DOI":"10.1111\/cea.12326","article-title":"IgE Antibodies to Alpha-Gal in the General Adult Population: Relationship with Tick Bites, Atopy, and Cat Ownership","volume":"44","author":"Vidal","year":"2014","journal-title":"Clin. Exp. Allergy"}],"container-title":["Diagnostics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2075-4418\/14\/13\/1403\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T15:08:40Z","timestamp":1760108920000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2075-4418\/14\/13\/1403"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,7,1]]},"references-count":43,"journal-issue":{"issue":"13","published-online":{"date-parts":[[2024,7]]}},"alternative-id":["diagnostics14131403"],"URL":"https:\/\/doi.org\/10.3390\/diagnostics14131403","relation":{},"ISSN":["2075-4418"],"issn-type":[{"value":"2075-4418","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,7,1]]}}}