Post-therapeutic relapse of psoriasis after CD11a blockade is associated with T cells and inflammatory myeloid DCs
| Autor: | Luke A. Hyder, Michelle A. Lowes, Leanne M. Johnson-Huang, Katherine C. Pierson, Cara A. Pensabene, Mayte Suárez-Fariñas, Mary Sullivan-Whalen, Inna Cueto, Tim Lentini, James G. Krueger, Patricia Gilleaudeau, Kejal R. Shah, Toyoko Kikuchi, Artemis Khatcherian |
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| Jazyk: | angličtina |
| Rok vydání: | 2012 |
| Předmět: |
Male
Myeloid T-Lymphocytes Efalizumab 030207 dermatology & venereal diseases 0302 clinical medicine Immunophenotyping Cell Movement Recurrence Cytotoxic T cell Myeloid Cells CD11a Antigen 0303 health sciences Multidisciplinary Antibodies Monoclonal hemic and immune systems Genomics 3. Good health medicine.anatomical_structure Medicine Tumor necrosis factor alpha Female medicine.drug Research Article CD14 Immune Cells Science Immunology chemical and pharmacologic phenomena CD11a Biology Antibodies Monoclonal Humanized Autoimmune Diseases 03 medical and health sciences Genome Analysis Tools Psoriasis medicine Humans 030304 developmental biology Inflammation Computational Biology Dendritic Cells medicine.disease Immune System Cell Migration Inhibition Immunologic Techniques Clinical Immunology Transcriptome |
| Zdroj: | PLoS ONE, Vol 7, Iss 2, p e30308 (2012) PLoS ONE |
| ISSN: | 1932-6203 |
| Popis: | UnlabelledTo 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 registrationClinicaltrials.gov NCT00115076. |
| Databáze: | OpenAIRE |
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