TY - JOUR
T1 - Resolved psoriasis lesions retain expression of a subset of disease-related genes
AU - Suárez-Farĩas, Mayte
AU - Fuentes-Duculan, Judilyn
AU - Lowes, Michelle A.
AU - Krueger, James G.
N1 - Funding Information:
This research was supported by the National Institutes of Health (NIH) Grant UL1 RR024143 from the National Center for Research Resources (NCRR) and the Milstein Program in Medical Research. MSF is partially supported by NIH Grant UL1 RR024143; MAL is supported by 1 K23 AR052404-01A1 and The Doris Duke Charitable Foundation. We thank Inna Novitskaya for technical assistance during the revision of the paper and Kristine Nograles for critical reading of the paper.
PY - 2011/2
Y1 - 2011/2
N2 - Psoriasis is a complex inflammatory disease that usually heals without visible scarring. Histological evaluation often suggests complete resolution, but reversal of genomic disease-associated alterations has not yet been defined. Gene expression profiling was used to determine the extent to which the psoriasis genes were reversed after 3 months of etanercept treatment in patients who responded to treatment. We reviewed the histology, leukocyte counts, and PCR data for inflammatory genes, to compare recovery of these parameters and the genomic studies. Many cellular markers do return close to nonlesional levels, although five inflammatory genes did not improve by 75% (IL-12p35, MX1, IL-22, IL-17, and IFNγ). Psoriasis-related genes with 75% improvement were defined as comprising a residual disease genomic profile, composed of 248 probe sets. Genes of interest in psoriasis tissue that did not return to baseline included LYVE-1, WNT5A, RAB31, and AQP9. It appears that even when the epidermal reaction in psoriasis is fully resolved, inflammation, as defined by expression of key cytokines and chemokines, is not completely resolved in treated lesions. We also found that structural cells of the skin continued to express molecular alterations, and that some subtle features of skin structure, for example, lymphatics, were not fully normalized with treatment.
AB - Psoriasis is a complex inflammatory disease that usually heals without visible scarring. Histological evaluation often suggests complete resolution, but reversal of genomic disease-associated alterations has not yet been defined. Gene expression profiling was used to determine the extent to which the psoriasis genes were reversed after 3 months of etanercept treatment in patients who responded to treatment. We reviewed the histology, leukocyte counts, and PCR data for inflammatory genes, to compare recovery of these parameters and the genomic studies. Many cellular markers do return close to nonlesional levels, although five inflammatory genes did not improve by 75% (IL-12p35, MX1, IL-22, IL-17, and IFNγ). Psoriasis-related genes with 75% improvement were defined as comprising a residual disease genomic profile, composed of 248 probe sets. Genes of interest in psoriasis tissue that did not return to baseline included LYVE-1, WNT5A, RAB31, and AQP9. It appears that even when the epidermal reaction in psoriasis is fully resolved, inflammation, as defined by expression of key cytokines and chemokines, is not completely resolved in treated lesions. We also found that structural cells of the skin continued to express molecular alterations, and that some subtle features of skin structure, for example, lymphatics, were not fully normalized with treatment.
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U2 - 10.1038/jid.2010.280
DO - 10.1038/jid.2010.280
M3 - Article
C2 - 20861854
AN - SCOPUS:78651401370
SN - 0022-202X
VL - 131
SP - 391
EP - 400
JO - Journal of Investigative Dermatology
JF - Journal of Investigative Dermatology
IS - 2
ER -