Resolved psoriasis lesions retain expression of a subset of disease-related genes.
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.
Suárez-Fariñas
Mayte
M
The Laboratory for Investigative Dermatology, The Rockefeller University, New York, New York 10065, USA.
Fuentes-Duculan
Judilyn
J
Lowes
Michelle A
MA
Krueger
James G
JG
D000328:Adult; D020346:Aquaporins / Q000235:genetics / Q000378:metabolism; D001706:Biopsy; D000068800:Etanercept; D020869:Gene Expression Profiling; D006801:Humans; D007074:Immunoglobulin G / Q000627:therapeutic use*; D011518:Proto-Oncogene Proteins / Q000235:genetics / Q000378:metabolism; D011565:Psoriasis / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism*; D018124:Receptors, Tumor Necrosis Factor / Q000627:therapeutic use*; D012867:Skin / Q000378:metabolism* / Q000473:pathology; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors; D033921:Vesicular Transport Proteins / Q000235:genetics / Q000378:metabolism; D051153:Wnt Proteins / Q000235:genetics / Q000378:metabolism; D000071818:Wnt-5a Protein; D020691:rab GTP-Binding Proteins / Q000235:genetics / Q000378:metabolism
C109669:AQP9 protein, human; D020346:Aquaporins; D007074:Immunoglobulin G; C119248:LYVE1 protein, human; D011518:Proto-Oncogene Proteins; C484190:RAB31 protein, human; D018124:Receptors, Tumor Necrosis Factor; D014409:Tumor Necrosis Factor-alpha; D033921:Vesicular Transport Proteins; C085389:WNT5A protein, human; D051153:Wnt Proteins; D000071818:Wnt-5a Protein; D020691:rab GTP-Binding Proteins; D000068800:Etanercept