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Therefore, we detected allergen\u2010specific IgE and IgG4 levels in patients with IgG4\u2010RD to clarify their contribution to IgG4\u2010RD pathogenesis.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>In total, 826 plasma samples from 370 patients with IgG4\u2010RD and 354 healthy controls were used to perform Phage Immunoprecipitation Sequencing. Follow\u2010up samples from 102 patients (median 3\u2009years) captured temporal dynamics. Machine learning (XGBoost) was used to identify key allergen peptides. ELISA was used for validation in 51 IgG4\u2010RD patients and 24 healthy controls, including an independent cohort of 20 treatment\u2010na\u00efve patients.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Abnormal IgE and IgG4 allergen reactivity was observed in IgG4\u2010RD patients. Enhanced responses to\n                      <jats:styled-content style=\"fixed-case\">\n                        <jats:italic>Apis mellifera<\/jats:italic>\n                      <\/jats:styled-content>\n                      and\n                      <jats:styled-content style=\"fixed-case\">\n                        <jats:italic>Arachis hypogaea<\/jats:italic>\n                      <\/jats:styled-content>\n                      were particularly prominent and correlated with lacrimal gland, parotid gland, paranasal, pulmonary, renal (\n                      <jats:styled-content style=\"fixed-case\">\n                        <jats:italic>A. mellifera<\/jats:italic>\n                      <\/jats:styled-content>\n                      ) and pancreatic (\n                      <jats:styled-content style=\"fixed-case\">\n                        <jats:italic>A. hypogaea<\/jats:italic>\n                      <\/jats:styled-content>\n                      ) involvement. XGBoost achieved an AUC of 0.91\u20130.96 and consistently ranked 10 peptides, mainly from bee, peanut, vespid\u2010venom and fish allergens. ELISA confirmed significantly elevated Ara h 1\u2010specific IgG4 in IgG4\u2010RD. Follow\u2010up sampling showed a global decline in reactivity to most top allergens and an IgE\u2010to\u2010IgG4 shift to\n                      <jats:styled-content style=\"fixed-case\">\n                        <jats:italic>Staphylococcus aureus<\/jats:italic>\n                      <\/jats:styled-content>\n                      peptides, suggesting therapy\u2010associated modulation and emerging tolerance.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Comprehensive pan\u2010allergen profiling suggests distinct IgE and IgG4 signatures in IgG4\u2010RD and links specific environmental antigens to organ\u2010selective disease patterns. These findings support a contributory role for aberrant allergen responses in IgG4\u2010RD pathogenesis and provide a foundation for biomarker development and targeted allergen\u2010based interventions, especially for future mechanistic investigations.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/all.70162","type":"journal-article","created":{"date-parts":[[2025,11,21]],"date-time":"2025-11-21T08:39:27Z","timestamp":1763714367000},"page":"1472-1486","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Allergen\u2010Specific\n                    <scp>IgE<\/scp>\n                    and\n                    <scp>IgG4<\/scp>\n                    Signatures in\n                    <scp>IgG4<\/scp>\n                    \u2010Related Disease Revealed by a Large\u2010Scale\n                    <scp>PhIP<\/scp>\n                    \u2010Seq Study"],"prefix":"10.1111","volume":"81","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9624-9545","authenticated-orcid":false,"given":"Zhan","family":"Li","sequence":"first","affiliation":[{"name":"Department of Clinical Laboratory, State Key Laboratory of Complex, Severe and Rare Diseases, Peking Union Medical College Hospital Chinese Academy of Medical Science and Peking Union Medical College  Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Songxin","family":"Yan","sequence":"additional","affiliation":[{"name":"Department of Clinical Laboratory, State Key Laboratory of Complex, Severe and Rare Diseases, Peking Union Medical College Hospital Chinese Academy of Medical Science and Peking Union Medical College  Beijing China"},{"name":"Department of Laboratory Medicine, Gene Diagnosis Research Center, the First Affiliated Hospital Fujian Medical University  Fuzhou 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Peking Union Medical College Hospital Chinese Academy of Medical Science and Peking Union Medical College  Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jingdi","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Clinical Laboratory, State Key Laboratory of Complex, Severe and Rare Diseases, Peking Union Medical College Hospital Chinese Academy of Medical Science and Peking Union Medical College  Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Siyu","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Clinical Laboratory, State Key Laboratory of Complex, Severe and Rare Diseases, Peking Union Medical College Hospital Chinese Academy of Medical Science and Peking Union Medical College  Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xinxin","family":"Feng","sequence":"additional","affiliation":[{"name":"Department of Clinical Laboratory, 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