{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T05:58:06Z","timestamp":1785391086764,"version":"3.55.0"},"reference-count":55,"publisher":"Wiley","license":[{"start":{"date-parts":[[2026,7,29]],"date-time":"2026-07-29T00:00:00Z","timestamp":1785283200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,7,29]],"date-time":"2026-07-29T00:00:00Z","timestamp":1785283200000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/100012545","name":"Foundation for Research in Science and the Humanities","doi-asserted-by":"publisher","award":["STEP\u20102022\u2010002"],"award-info":[{"award-number":["STEP\u20102022\u2010002"]}],"id":[{"id":"10.13039\/100012545","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100012774","name":"Innovationsfonden","doi-asserted-by":"publisher","award":["909000065B"],"award-info":[{"award-number":["909000065B"]}],"id":[{"id":"10.13039\/100012774","id-type":"DOI","asserted-by":"publisher"}]}],"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>Intralymphatic immunotherapy (ILIT) has been investigated for two decades in small clinical trials, typically using native allergens adsorbed to aluminium hydroxide (alum). This randomised, double\u2010blind, placebo\u2010controlled study evaluated the safety and efficacy of ILIT with a grass pollen allergoid formulated with microcrystalline tyrosine (MCT).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      Sixty adults with grass pollen\u2013induced allergic rhinoconjunctivitis (ARC) were randomised to receive ILIT with grass allergoid (equivalent to 60\u2009ng Phl p 5;\n                      <jats:italic>n<\/jats:italic>\n                      \u2009=\u200931) or placebo (\n                      <jats:italic>n<\/jats:italic>\n                      \u2009=\u200929). Three ultrasound\u2010guided injections (100\u2009\u03bcL) were administered into inguinal lymph nodes at 4\u2010week intervals in early 2022. The primary endpoint was the combined symptom and medication score (cSMS), recorded daily during the 2022 and 2023 grass pollen seasons. Secondary endpoints included safety, Rhinitis Quality of Life Questionnaire (RQLQ), serology, spirometry, fractional exhaled nitric oxide (FeNO), and skin\u2010prick testing (SPT). An open\u2010label extension, in which the placebo participants received active ILIT, was conducted in 2024.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      ILIT was well tolerated, with no severe adverse events (SAEs). Mild local reactions (wheal, erythema, swelling) occurred after 50 of 93 active injections (53.8%), and three moderate reactions (3.2%) were reported. In the placebo group, one mild and no moderate reactions occurred. No allergen\u2010specific systemic reactions were observed. Compared with placebo, ILIT reduced cSMS by 33% in 2022 (\n                      <jats:italic>p<\/jats:italic>\n                      \u2009&gt;\u20090.05) and 50% in 2023 (\n                      <jats:italic>p<\/jats:italic>\n                      \u2009&lt;\u20090.05). RQLQ improved with relative reductions of 22% and 13% (\n                      <jats:italic>p<\/jats:italic>\n                      \u2009&gt;\u20090.05), respectively.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>ILIT with a grass pollen allergoid formulated with MCT was well tolerated and associated with clinically relevant reductions in symptom and medication use in grass pollen\u2013induced ARC. In this small study cohort, ILIT proved to be efficient and safe, but further optimisation of dosing regimens should follow.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/all.70463","type":"journal-article","created":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T05:00:45Z","timestamp":1785387645000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Efficacy and Safety of Intralymphatic Immunotherapy With Grass Allergoid and Microcrystalline Tyrosine: A Double\u2010Blind Randomised Placebo\u2010Controlled Trial"],"prefix":"10.1111","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9464-3562","authenticated-orcid":false,"given":"Lara","family":"\u0160o\u0161i\u0107","sequence":"first","affiliation":[{"name":"Department of Dermatology University of Zurich  Zurich Switzerland"},{"name":"Department of Dermatology University Hospital Zurich  Zurich Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stephan C.","family":"Flory","sequence":"additional","affiliation":[{"name":"Department of Dermatology University of Zurich  Zurich Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0469-7661","authenticated-orcid":false,"given":"Claudia C. V.","family":"Lang","sequence":"additional","affiliation":[{"name":"Department of Dermatology University of Zurich  Zurich Switzerland"},{"name":"Department of Dermatology University Hospital Zurich  Zurich Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Emma C.","family":"Widmer","sequence":"additional","affiliation":[{"name":"Department of Dermatology University of Zurich  Zurich Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexandra","family":"Chabot","sequence":"additional","affiliation":[{"name":"Department of Dermatology University of Zurich  Zurich Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4558-2943","authenticated-orcid":false,"given":"Johannes M.","family":"Schmid","sequence":"additional","affiliation":[{"name":"Department of Clinical Medicine Aarhus University  Aarhus Denmark"},{"name":"Department of Respiratory Diseases and Allergy Aarhus University  Aarhus Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tobias","family":"Andermatt","sequence":"additional","affiliation":[{"name":"Department of Dermatology University of Zurich  Zurich Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0002-8086-3713","authenticated-orcid":false,"given":"David","family":"Melillo","sequence":"additional","affiliation":[{"name":"Department of Dermatology University of Zurich  Zurich Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8835-2523","authenticated-orcid":false,"given":"Bjarke","family":"Hviid\u2010Vyff","sequence":"additional","affiliation":[{"name":"Department of Clinical Medicine Aarhus University  Aarhus Denmark"},{"name":"Department of Respiratory Diseases and Allergy Aarhus University  Aarhus Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4581-7335","authenticated-orcid":false,"given":"Maibritt","family":"Mardahl","sequence":"additional","affiliation":[{"name":"Data\u2010Set\u2010Go ApS  Silkeborg Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3215-3370","authenticated-orcid":false,"given":"Peter","family":"Schmid\u2010Grendelmeier","sequence":"additional","affiliation":[{"name":"Department of Dermatology University of Zurich  Zurich Switzerland"},{"name":"Department of Dermatology University Hospital Zurich  Zurich Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3863-8766","authenticated-orcid":false,"given":"Thomas M.","family":"K\u00fcndig","sequence":"additional","affiliation":[{"name":"Department of Dermatology University of Zurich  Zurich Switzerland"},{"name":"Department of Dermatology University Hospital Zurich  Zurich Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6743-7931","authenticated-orcid":false,"given":"Hans J\u00fcrgen","family":"Hoffmann","sequence":"additional","affiliation":[{"name":"Department of Clinical Medicine Aarhus University  Aarhus Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5055-6299","authenticated-orcid":false,"given":"P\u00e5l","family":"Johansen","sequence":"additional","affiliation":[{"name":"Department of Dermatology University of Zurich  Zurich Switzerland"},{"name":"Department of Dermatology University Hospital Zurich  Zurich Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,7,29]]},"reference":[{"key":"e_1_2_10_2_1","doi-asserted-by":"publisher","DOI":"10.1097\/ACI.0b013e3283310ff7"},{"key":"e_1_2_10_3_1","doi-asserted-by":"publisher","DOI":"10.1111\/all.16138"},{"key":"e_1_2_10_4_1","doi-asserted-by":"publisher","DOI":"10.1111\/all.16325"},{"key":"e_1_2_10_5_1","doi-asserted-by":"publisher","DOI":"10.1097\/aci.0000000000000857"},{"key":"e_1_2_10_6_1","doi-asserted-by":"publisher","DOI":"10.1159\/000531332"},{"key":"e_1_2_10_7_1","doi-asserted-by":"publisher","DOI":"10.1111\/cea.14138"},{"key":"e_1_2_10_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.anai.2018.07.010"},{"key":"e_1_2_10_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaci.2018.05.030"},{"key":"e_1_2_10_10_1","doi-asserted-by":"publisher","DOI":"10.1111\/all.15042"},{"key":"e_1_2_10_11_1","doi-asserted-by":"publisher","DOI":"10.1111\/all.15042"},{"key":"e_1_2_10_12_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12931\u2010016\u20100324\u20109"},{"key":"e_1_2_10_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaci.2012.10.056"},{"key":"e_1_2_10_14_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaci.2019.11.017"},{"key":"e_1_2_10_15_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13601\u2010016\u20100107\u2010x"},{"key":"e_1_2_10_16_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0803725105"},{"key":"e_1_2_10_17_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaci.2020.07.002"},{"key":"e_1_2_10_18_1","doi-asserted-by":"publisher","DOI":"10.1111\/all.14642"},{"key":"e_1_2_10_19_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.anai.2020.04.030"},{"key":"e_1_2_10_20_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13223\u2010020\u201000427\u2010z"},{"key":"e_1_2_10_21_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaci.2013.07.033"},{"key":"e_1_2_10_22_1","doi-asserted-by":"publisher","DOI":"10.1111\/cea.14307"},{"key":"e_1_2_10_23_1","doi-asserted-by":"publisher","DOI":"10.1111\/all.70148"},{"key":"e_1_2_10_24_1","doi-asserted-by":"publisher","DOI":"10.3389\/fmed.2025.1709531"},{"key":"e_1_2_10_25_1","doi-asserted-by":"publisher","DOI":"10.1097\/md.0000000000040589"},{"key":"e_1_2_10_26_1","doi-asserted-by":"publisher","DOI":"10.4193\/Rhin20.572"},{"key":"e_1_2_10_27_1","doi-asserted-by":"publisher","DOI":"10.1155\/2023\/9377518"},{"key":"e_1_2_10_28_1","doi-asserted-by":"publisher","DOI":"10.2500\/aap.2021.42.210028"},{"key":"e_1_2_10_29_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaci.2013.11.036"},{"key":"e_1_2_10_30_1","doi-asserted-by":"publisher","DOI":"10.1111\/cea.12657"},{"key":"e_1_2_10_31_1","doi-asserted-by":"publisher","DOI":"10.23822\/EurAnnACI.1764\u20101489.142"},{"key":"e_1_2_10_32_1","doi-asserted-by":"publisher","DOI":"10.23822\/EurAnnACI.1764\u20101489.100"},{"key":"e_1_2_10_33_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaip.2020.12.008"},{"key":"e_1_2_10_34_1","doi-asserted-by":"publisher","DOI":"10.4161\/hv.24631"},{"key":"e_1_2_10_35_1","doi-asserted-by":"publisher","DOI":"10.1159\/000503684"},{"key":"e_1_2_10_36_1","doi-asserted-by":"publisher","DOI":"10.2217\/imt\u20102018\u20100143"},{"key":"e_1_2_10_37_1","doi-asserted-by":"publisher","DOI":"10.1159\/000343026"},{"key":"e_1_2_10_38_1","doi-asserted-by":"publisher","DOI":"10.1111\/all.12860"},{"key":"e_1_2_10_39_1","doi-asserted-by":"publisher","DOI":"10.2217\/imt\u20102019\u20100086"},{"key":"e_1_2_10_40_1","doi-asserted-by":"publisher","DOI":"10.1002\/clt2.12037"},{"key":"e_1_2_10_41_1","doi-asserted-by":"publisher","DOI":"10.1159\/000233157"},{"key":"e_1_2_10_42_1","doi-asserted-by":"publisher","DOI":"10.1002\/jat.869"},{"key":"e_1_2_10_43_1","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2020.594911"},{"key":"e_1_2_10_44_1","doi-asserted-by":"publisher","DOI":"10.18176\/jiaci.0349"},{"key":"e_1_2_10_45_1","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.1800035"},{"key":"e_1_2_10_46_1","doi-asserted-by":"publisher","DOI":"10.1111\/all.16640"},{"key":"e_1_2_10_47_1","doi-asserted-by":"publisher","DOI":"10.1111\/all.15788"},{"key":"e_1_2_10_48_1","doi-asserted-by":"publisher","DOI":"10.1002\/iid3.585"},{"key":"e_1_2_10_49_1","doi-asserted-by":"publisher","DOI":"10.1111\/all.12518"},{"key":"e_1_2_10_50_1","doi-asserted-by":"publisher","DOI":"10.1186\/1471\u20102466\u201014\u201063"},{"key":"e_1_2_10_51_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaci.2003.09.008"},{"key":"e_1_2_10_52_1","doi-asserted-by":"publisher","DOI":"10.1097\/WOX.0b013e31826a10cf"},{"key":"e_1_2_10_53_1","doi-asserted-by":"publisher","DOI":"10.1111\/all.12383"},{"key":"e_1_2_10_54_1","doi-asserted-by":"publisher","DOI":"10.1111\/pai.12660"},{"key":"e_1_2_10_55_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12931\u2010021\u201001766\u20100"},{"key":"e_1_2_10_56_1","doi-asserted-by":"publisher","DOI":"10.1111\/all.16491"}],"container-title":["Allergy"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/all.70463","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1111\/all.70463","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/all.70463","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T05:00:47Z","timestamp":1785387647000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/all.70463"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,7,29]]},"references-count":55,"alternative-id":["10.1111\/all.70463"],"URL":"https:\/\/doi.org\/10.1111\/all.70463","archive":["Portico"],"relation":{},"ISSN":["0105-4538","1398-9995"],"issn-type":[{"value":"0105-4538","type":"print"},{"value":"1398-9995","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,7,29]]},"assertion":[{"value":"2026-03-13","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-07-21","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-07-29","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"all.70463"}}