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Currently, systemic therapy is recommended to patients with an Eczema Area and Severity Index (EASI)\u2009\u2265\u200916. Previous studies have demonstrated an improved treatment response to the anti\u2010interleukin (IL)\u201013 antibody tralokinumab in AD subgroups with elevated levels of the IL\u201013\u2010related biomarkers dipeptidyl\u2010peptidase (DPP)\u20104 and periostin.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      Herein, 373 AD patients aged \u226512\u2009years were stratified by IL\u201013\n                      <jats:sup>high<\/jats:sup>\n                      , periostin\n                      <jats:sup>high<\/jats:sup>\n                      and DPP\u20104\n                      <jats:sup>high<\/jats:sup>\n                      endotypes using cross\u2010sectional data from the ProRaD cohort Bonn. \u201cHigh\u201d was defined as &gt;80th quantile of 47 non\u2010atopic controls. We analyzed endotype\u2010phenotype associations using machine\u2010learning gradient boosting compared to logistic regression.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Atopic dermatitis severity and eosinophils correlated with IL\u201013 and periostin levels. Correlations of IL\u201013 with EASI were stronger in patients with increased (rs\u00a0=\u00a00.482) than with normal (rs\u00a0=\u00a00.342) periostin levels. We identified eosinophilia &gt;6% and an EASI range of 5.5\u201317 dependent on the biomarker combination to be associated with increasing probabilities of biomarker\n                      <jats:sup>high<\/jats:sup>\n                      endotypes. Also patients with mild\u2010to\u2010low\u2010moderate severity (EASI\u2009&lt;\u200916) featured increased biomarkers (IL\u201013\n                      <jats:sup>high<\/jats:sup>\n                      : 41%, periostin\n                      <jats:sup>high<\/jats:sup>\n                      : 48.4%, DPP\u20104\n                      <jats:sup>high<\/jats:sup>\n                      : 22.3%). Herthoge sign (adjusted Odds Ratio (aOR)\u00a0=\u00a01.89, 95% Confidence Interval (CI) [1.14\u20133.14]) and maternal allergic rhinitis (aOR\u00a0=\u00a02.79\u20134.47) increased the probability of an IL\u201013\n                      <jats:sup>high<\/jats:sup>\n                      \u2010endotype, \u201cdirty neck\u201d (aOR\u00a0=\u00a02.83 [1.32\u20136.07]), orbital darkening (aOR\u00a0=\u00a02.43 [1.08\u20135.50]), keratosis pilaris (aOR\u00a0=\u00a02.21 [1.1\u20134.42]) and perleche (aOR\u00a0=\u00a03.44 [1.72\u20136.86]) of a DPP\u20104\n                      <jats:sup>high<\/jats:sup>\n                      \u2010endotype.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>A substantial proportion of patients with EASI\u2009&lt;\u200916 featured high biomarker levels suggesting systemic impact of skin inflammation already below the current cut\u2010off for systemic therapy. Our findings facilitate the identification of patients with distinct endotypes potentially linked to response to IL\u201013\u2010targeted therapy.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/all.15647","type":"journal-article","created":{"date-parts":[[2023,1,17]],"date-time":"2023-01-17T06:12:32Z","timestamp":1673935952000},"page":"1554-1569","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":33,"title":["IL\u201013, periostin and dipeptidyl\u2010peptidase\u20104 reveal endotype\u2010phenotype associations in atopic dermatitis"],"prefix":"10.1111","volume":"78","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6053-1530","authenticated-orcid":false,"given":"Laura","family":"Maintz","sequence":"first","affiliation":[{"name":"Department of Dermatology and Allergy University Hospital Bonn  Bonn Germany"},{"name":"Christine K\u00fchne Center for Allergy Research and Education Davos (CK\u2010CARE)  Davos 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