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Omalizumab normalizes the gene expression signature of lesional skin in patients with chronic spontaneous urticaria: A randomized, double‐blind, placebo‐controlled study
Author(s) -
Metz Martin,
Torene Rebecca,
Kaiser Sergio,
Beste Michael T.,
Staubach Petra,
Bauer Andrea,
Brehler Randolf,
Gericke Janine,
Letzkus Martin,
Hartmann Nicole,
Erpenbeck Veit J.,
Maurer Marcus
Publication year - 2019
Publication title -
allergy
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 3.363
H-Index - 173
eISSN - 1398-9995
pISSN - 0105-4538
DOI - 10.1111/all.13547
Subject(s) - omalizumab , medicine , placebo , double blind , chronic urticaria , randomized controlled trial , dermatology , immunology , pathology , immunoglobulin e , antibody , alternative medicine
Background Omalizumab, a humanized recombinant monoclonal anti‐IgE antibody, proved to be effective in patients with chronic spontaneous urticaria ( CSU ), including severe and treatment‐refractory CSU . Here, we report omalizumab's effect on gene expression in skin biopsies from CSU patients enrolled in a double‐blind, placebo‐controlled study. Methods Chronic spontaneous urticaria patients (18‐75 years) were randomized to either 300 mg omalizumab (n = 20) or placebo (n = 10) administered s.c. every 4 weeks for 12 weeks ( NCT 01599637). Lesional and nonlesional skin biopsies were collected from the same area of consenting patients and assessed at baseline and on Day 85 compared with skin biopsies from the same area of 10 untreated healthy volunteers ( HV s). Gene expression data were generated using Affymetrix HG ‐U133Plus2.0 microarrays. Statistical analyses were performed using R packages. Results At baseline, 63 transcripts were differentially expressed between lesional and nonlesional skin. Two‐thirds of these lesional signatures were also differentially expressed between lesional and HV skin. Upon treatment with omalizumab, >75% of lesional signatures changed to reflect nonlesional skin expression levels (different vs placebo, P < 0.01). Transcripts upregulated in lesional skin (vs nonlesional and/or HV skin) suggested increased mast cell/leukocyte infiltration ( FCER 1G, C3 AR 1, CD 93, S100A8, and S100A9), increased oxidative stress, vascularization ( CYR 61), and skin repair events ( KRT 6A, KRT 16). Lesional signatures were not modulated by treatment in nonresponders (defined based on UAS 7 longitudinal changes ≥16). Conclusion Omalizumab, in treatment responders, reverted transcriptional signatures associated with CSU lesion phenotype to reflect nonlesional/ HV expression levels; this is consistent with observed omalizumab‐mediated clinical improvement observed in patients with CSU .