title: Histological Stratification of Thick and Thin Plaque Psoriasis Explores Molecular Phenotypes with Clinical Implications.
abstract: Psoriasis, which presents as red, scaly patches on the body, is a common, autoimmune skin disease that affects 2 to 3 percent of the world population. To leverage recent molecular findings into the personalized treatment of psoriasis, we need a strategy that integrates clinical stratification with molecular phenotyping. In this study, we sought to stratify psoriasis patients by histological measurements of epidermal thickness, and to compare their molecular characterizations by gene expression, serum cytokines, and response to biologics. We obtained histological measures of epidermal thickness in a cohort of 609 psoriasis patients, and identified a mixture of two subpopulations-thick and thin plaque psoriasis-from which they were derived. This stratification was verified in a subcohort of 65 patients from a previously published study with significant differences in inflammatory cell infiltrates in the psoriatic skin. Thick and thin plaque psoriasis shared 84.8% of the meta-analysis-derived psoriasis transcriptome, but a stronger dysregulation of the meta-analysis-derived psoriasis transcriptome was seen in thick plaque psoriasis on microarray. RT-PCR revealed that gene expression in thick and thin plaque psoriasis was different not only within psoriatic lesional skin but also in peripheral non-lesional skin. Additionally, differences in circulating cytokines and their changes in response to biologic treatments were found between the two subgroups. All together, we were able to integrate histological stratification with molecular phenotyping as a way of exploring clinical phenotypes with different expression levels of the psoriasis transcriptome and circulating cytokines.
authors.affiliation: Laboratory for Investigative Dermatology, The Rockefeller University, New York, New York, United States of America.
authors.forename: Jaehwan
authors.initials: J
authors.lastname: Kim
authors.affiliation: Laboratory for Investigative Dermatology, The Rockefeller University, New York, New York, United States of America; Harvard University, Cambridge, Massachusetts, United States of America.
authors.forename: Pranay
authors.initials: P
authors.lastname: Nadella
authors.affiliation: Laboratory for Investigative Dermatology, The Rockefeller University, New York, New York, United States of America; School of Medicine, Stony Brook University, Stony Brook, New York, United States of America.
authors.forename: Dong Joo
authors.initials: DJ
authors.lastname: Kim
authors.affiliation: Immunology & Biomarkers, Janssen Research & Development, Radnor, Pennsylvania, United States of America.
authors.forename: Carrie
authors.initials: C
authors.lastname: Brodmerkel
authors.affiliation: The Center for Clinical and Translational Science, The Rockefeller University, New York, New York, United States of America.
authors.forename: Joel
authors.initials: J
authors.lastname: Correa da Rosa
authors.affiliation: Laboratory for Investigative Dermatology, The Rockefeller University, New York, New York, United States of America.
authors.forename: James G
authors.initials: JG
authors.lastname: Krueger
authors.affiliation: The Center for Clinical and Translational Science, The Rockefeller University, New York, New York, United States of America; Icahn School of Medicine at Mount Sinai, New York, New York, United States of America.
authors.forename: Mayte
authors.initials: M
authors.lastname: Suárez-Fariñas
mesh_terms: D000328:Adult; D016207:Cytokines / Q000097:blood; D004817:Epidermis / Q000378:metabolism / Q000473:pathology; D005260:Female; D020869:Gene Expression Profiling; D006801:Humans; D008297:Male; D008875:Middle Aged; D010641:Phenotype; D011565:Psoriasis / Q000378:metabolism / Q000473:pathology*; D012097:Repressor Proteins / Q000235:genetics / Q000378:metabolism; D059467:Transcriptome
chemical_list: D016207:Cytokines; C543450:MXD3 protein, human; D012097:Repressor Proteins