{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,14]],"date-time":"2026-08-14T13:27:37Z","timestamp":1786714057185,"version":"build-2736575974"},"reference-count":30,"publisher":"Wiley","license":[{"start":{"date-parts":[[2026,8,14]],"date-time":"2026-08-14T00:00:00Z","timestamp":1786665600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2026,8,14]],"date-time":"2026-08-14T00:00:00Z","timestamp":1786665600000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Allergy"],"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Navigating the more than 550 inborn errors of immunity (IEI) requires efficient diagnostic reasoning. Information theory suggests questions should be prioritized by their capacity to reduce diagnostic uncertainty (entropy); yet whether experts or large language models (LLMs) optimize for information gain remains unquantified.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>We compared expert clinician and LLM diagnostic prioritization strategies using an information\u2010theoretic framework.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Fifteen immunologists and six LLMs (ChatGPT, Claude, Gemini, Grok, DeepSeek, and Llama) ranked 35 diagnostic questions by efficiency. Shannon's entropy was used to estimate expected information gain (EIG) for each question. Agreement was assessed via Spearman correlations, consensus ranking, and principal components analysis (PCA).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Clinician consensus rankings strongly correlated with estimated information gain (Spearman\n                      <jats:italic>\u03c1<\/jats:italic>\n                      \u2009=\u2009\u22120.71,\n                      <jats:italic>p<\/jats:italic>\n                      \u2009&lt;\u20090.001). \u201cAge at onset?\u201d ranked first by clinicians, provided the highest information gain (2.29 bits), reducing diagnostic uncertainty by 80%. Clinicians and LLMs showed strong agreement on top\u2010tier discriminators (Spearman\n                      <jats:italic>\u03c1<\/jats:italic>\n                      \u2009=\u20090.73,\n                      <jats:italic>p<\/jats:italic>\n                      \u2009&lt;\u20090.001). However, PCA revealed a distinct LLM cluster; clinicians prioritized bedside\/history questions, whereas LLMs favored syndromic and laboratory features. Optimal questioning reached diagnostic confidence in 4\u20135 steps, approaching the theoretical minimum.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Expert clinicians implicitly approximate information\u2010theoretic optimization in IEI diagnostics. While LLMs share a core heuristic for high\u2010yield questions, divergence in mid\u2010sequence reasoning suggests a shift from experiential heuristics to probabilistic data\u2010matching. This framework provides a principled basis for training AI\u2010assisted tools that mirror expert diagnostic logic.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/all.70483","type":"journal-article","created":{"date-parts":[[2026,8,14]],"date-time":"2026-08-14T12:31:31Z","timestamp":1786710691000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["How to Train Your Chatbot: Information\u2010Theoretic Foundations of Diagnostic Questioning in Inborn Errors of Immunity"],"prefix":"10.1111","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3730-4150","authenticated-orcid":false,"given":"Saul O.","family":"Lugo Reyes","sequence":"first","affiliation":[{"name":"Immune Deficiencies Research Laboratory National Institute of Pediatrics, Health Secretariat  Mexico City Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Estefan\u00eda","family":"V\u00e1squez Echeverri","sequence":"additional","affiliation":[{"name":"Unidad M\u00e9dica Quir\u00fargica Otorrinolaringolog\u00eda\u2010UNIMEQ\u2010ORL  Bogot\u00e1 Colombia"},{"name":"Facultad de Medicina Universidad EIA  Medell\u00edn Colombia"},{"name":"Inborn Errors of Immunity Group, Department of Microbiology and Parasitology, School of Medicine University of Antioquia UdeA  Medellin Colombia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Juan Carlos","family":"Bustamante Ogando","sequence":"additional","affiliation":[{"name":"Immune Deficiencies Research Laboratory National Institute of Pediatrics, Health Secretariat  Mexico City Mexico"},{"name":"Clinical Immunology Service National Institute of Pediatrics, Health Secretariat  Mexico City Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1478-8401","authenticated-orcid":false,"given":"Lina M.","family":"Castano\u2010Jaramillo","sequence":"additional","affiliation":[{"name":"Pediatric Allergy and Clinical Immunology HOMI Hospital Pedi\u00e1trico la Misericordia  Bogot\u00e1 Colombia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2936-3679","authenticated-orcid":false,"given":"Natalia","family":"V\u00e9lez Tirado","sequence":"additional","affiliation":[{"name":"Pediatric Allergy and Clinical Immunology HOMI Hospital Pedi\u00e1trico la Misericordia  Bogot\u00e1 Colombia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Edna","family":"Venegas Montoya","sequence":"additional","affiliation":[{"name":"Immunology Service, Hospital General Regional No. 1 Instituto Mexicano del Seguro Social (IMSS)  Culiac\u00e1n M\u00e9xico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alejandro","family":"Tarango Garc\u00eda","sequence":"additional","affiliation":[{"name":"Immune Deficiencies Research Laboratory National Institute of Pediatrics, Health Secretariat  Mexico City Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"H\u00e9ctor","family":"G\u00f3mez Tello","sequence":"additional","affiliation":[{"name":"Allergology Department Hospital de la Ni\u00f1ez Poblana  Puebla Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alejandro","family":"Palma","sequence":"additional","affiliation":[{"name":"Division of Immunology IWK Health Centre, Dalhousie University  Halifax Nova Scotia Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mat\u00edas","family":"Oleastro","sequence":"additional","affiliation":[{"name":"Clinical Immunology Service Hospital de Pediatr\u00eda SAMIC \u2018Prof. Dr. Juan P. Garrahan\u2019  Buenos Aires Argentina"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Selma Cecilia","family":"Scheffler Mendoza","sequence":"additional","affiliation":[{"name":"Clinical Immunology Service National Institute of Pediatrics, Health Secretariat  Mexico City Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sara Elva","family":"Espinosa\u2010Padilla","sequence":"additional","affiliation":[{"name":"Immune Deficiencies Research Laboratory National Institute of Pediatrics, Health Secretariat  Mexico City Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eduardo","family":"Guan\u00ed Guerra","sequence":"additional","affiliation":[{"name":"Department of Medicine University of Guanajuato  Guanajuato Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hanadys","family":"Ale","sequence":"additional","affiliation":[{"name":"Division of Immunology, Allergy, and Rheumatology Joe DiMaggio Children's Hospital, Memorial Healthcare System  Hollywood Florida USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7609-3923","authenticated-orcid":false,"given":"Marco A.","family":"Yamazaki\u2010Nakashimada","sequence":"additional","affiliation":[{"name":"Clinical Immunology Service National Institute of Pediatrics, Health Secretariat  Mexico City Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kathleen E.","family":"Sullivan","sequence":"additional","affiliation":[{"name":"Division of Allergy and Immunology, Children's Hospital of Philadelphia Perelman School of Medicine at the University of Pennsylvania  Philadelphia Pennsylvania USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3144-1864","authenticated-orcid":false,"given":"Chiharu","family":"Murata","sequence":"additional","affiliation":[{"name":"Research Methodology Department National Institute of Pediatrics, Health Secretariat  Mexico City Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,8,14]]},"reference":[{"key":"e_1_2_12_2_1","doi-asserted-by":"publisher","DOI":"10.70962\/JHI.20250002"},{"key":"e_1_2_12_3_1","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2015.00142"},{"issue":"5","key":"e_1_2_12_4_1","doi-asserted-by":"crossref","first-page":"1186","DOI":"10.1016\/j.jaci.2015.04.049","article-title":"Practice Parameter for the Diagnosis and Management of Primary Immunodeficiency","volume":"136","author":"Bonilla F. 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