185 High-dimensional analysis identifies variably persistent skin-homing Th2/Tc2 populations in AD patients under remission with dupilumab

Background: Dupilumab is an effective treatment in patients with atopic dermatitis (AD), yet certain pathogenic CRTH2+ThA cells are reported to resist skin. High-dimensional analysis of FACS may provide novel insights into disease pathogenesis. Objectives: To study the effects dupilumab ex vivo on circulating effector CD4 and CD8 moderate-to-severe AD. Materials Methods: We used multiparametric analyze PBMCs from two patient cohorts (untreated versus treated AD remission) healthy subjects, applying high-dimensional T identify subsets elevated (multiple Mann-Whitney, Dunn's multiple comparisons), then compared between 3 groups (one-way ANOVA). Results: profiled 18 meta-clusters cells. found 6 1 sub-populations significantly subjects. In under remission, only one cluster skin-homing among these was persistently above subjects memory CLAhighestGATA3int-hiCRTH2- HLADRlo-int. The remaining cell clusters were statistically comparable during including activated CLAhighest (GATA3loCRTH2v.loCCR6lo) (GATA3int-hiCRTH2loCCR6v.lo) cells, as well naïve CLA- populations. CXCR3 negative clusters. A trend for increased GATA3v.loCRTH2hiCCR6v.lo patients, while other CRTH2hi not different groups. Conclusion: remission dupilumab, persistent Th2 GATA3int-hi but CRTH2- highlighting centrality this master transcription factor a need further elucidate role CRTH2+Th2A pathogenesis