title: Post-therapeutic relapse of psoriasis after CD11a blockade is associated with T cells and inflammatory myeloid DCs.
abstract: To understand the development of new psoriasis lesions, we studied a group of moderate-to-severe psoriasis patients who experienced a relapse after ceasing efalizumab (anti-CD11a, Raptiva, Genentech). There were increased CD3(+) T cells, neutrophils, CD11c(+) and CD83(+) myeloid dendritic cells (DCs), but no increase in CD1c(+) resident myeloid DCs. In relapsed lesions, there were many CD11c(+)CD1c(-), inflammatory myeloid DCs identified by TNFSF10/TRAIL, TNF, and iNOS. CD11c(+) cells in relapsed lesions co-expressed CD14 and CD16 in situ. Efalizumab induced an improvement in many psoriasis genes, and during relapse, the majority of these genes reversed back to a lesional state. Gene Set Enrichment Analysis (GSEA) of the transcriptome of relapsed tissue showed that many of the gene sets known to be present in psoriasis were also highly enriched in relapse. Hence, on ceasing efalizumab, T cells and myeloid cells rapidly enter the skin to cause classic psoriasis.
  
  
  BACKGROUND
  Clinicaltrials.gov NCT00115076.
authors.affiliation: Laboratory for Investigative Dermatology, The Rockefeller University, New York, New York, United States of America.
authors.forename: Leanne M
authors.initials: LM
authors.lastname: Johnson-Huang
authors.forename: Cara A
authors.initials: CA
authors.lastname: Pensabene
authors.forename: Kejal R
authors.initials: KR
authors.lastname: Shah
authors.forename: Katherine C
authors.initials: KC
authors.lastname: Pierson
authors.forename: Toyoko
authors.initials: T
authors.lastname: Kikuchi
authors.forename: Tim
authors.initials: T
authors.lastname: Lentini
authors.forename: Patricia
authors.initials: P
authors.lastname: Gilleaudeau
authors.forename: Mary
authors.initials: M
authors.lastname: Sullivan-Whalen
authors.forename: Inna
authors.initials: I
authors.lastname: Cueto
authors.forename: Artemis
authors.initials: A
authors.lastname: Khatcherian
authors.forename: Luke A
authors.initials: LA
authors.lastname: Hyder
authors.forename: Mayte
authors.initials: M
authors.lastname: Suárez-Fariñas
authors.forename: James G
authors.initials: JG
authors.lastname: Krueger
authors.forename: Michelle A
authors.initials: MA
authors.lastname: Lowes
mesh_terms: D000911:Antibodies, Monoclonal / Q000627:therapeutic use*; D061067:Antibodies, Monoclonal, Humanized; D040881:CD11a Antigen / Q000187:drug effects*; D002464:Cell Migration Inhibition; D002465:Cell Movement; D003713:Dendritic Cells / Q000276:immunology / Q000473:pathology; D005260:Female; D006801:Humans; D016130:Immunophenotyping; D007249:Inflammation / Q000473:pathology; D008297:Male; D022423:Myeloid Cells; D011565:Psoriasis / Q000188:drug therapy / Q000235:genetics / Q000473:pathology; D012008:Recurrence; D013601:T-Lymphocytes / Q000276:immunology / Q000473:pathology; D059467:Transcriptome
chemical_list: D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D040881:CD11a Antigen; C472181:efalizumab