HOMEPRODUCTSCOMPANYCONTACTFAQResearchDictionaryPharmaSign Up FREE or Login

Post-therapeutic relapse of psoriasis after CD11a blockade is associated with T cells and inflammatory myeloid DCs.

AbstractUNLABELLED:
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.
TRIAL REGISTRATION:
Clinicaltrials.gov NCT00115076.
AuthorsLeanne M Johnson-Huang, Cara A Pensabene, Kejal R Shah, Katherine C Pierson, Toyoko Kikuchi, Tim Lentini, Patricia Gilleaudeau, Mary Sullivan-Whalen, Inna Cueto, Artemis Khatcherian, Luke A Hyder, Mayte Suárez-Fariñas, James G Krueger, Michelle A Lowes
JournalPloS one (PLoS One) Vol. 7 Issue 2 Pg. e30308 ( 2012) ISSN: 1932-6203 [Electronic] United States
PMID22348003 (Publication Type: Clinical Trial, Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)
Chemical References
  • Antibodies, Monoclonal
  • Antibodies, Monoclonal, Humanized
  • CD11a Antigen
  • efalizumab
Topics
  • Antibodies, Monoclonal (therapeutic use)
  • Antibodies, Monoclonal, Humanized
  • CD11a Antigen (drug effects)
  • Cell Migration Inhibition
  • Cell Movement
  • Dendritic Cells (immunology, pathology)
  • Female
  • Humans
  • Immunophenotyping
  • Inflammation (pathology)
  • Male
  • Myeloid Cells
  • Psoriasis (drug therapy, genetics, pathology)
  • Recurrence
  • T-Lymphocytes (immunology, pathology)
  • Transcriptome

Join CureHunter, for free Research Interface BASIC access!

Take advantage of free CureHunter research engine access to explore the best drug and treatment options for any disease. Find out why thousands of doctors, pharma researchers and patient activists around the world use CureHunter every day.
Realize the full power of the drug-disease research graph!


Choose Username:
Email:
Password:
Verify Password:
Enter Code Shown: