Abstract
BackgroundPrevious studies of epidermal kinetics in psoriasis have relied on invasive biopsy procedures or the use of radioactive labels. We previously developed a non-invasive method for measuring keratin synthesis in human skin using deuterated water labeling, serial collection of tape strips and measurement of deuterium enrichment in protein by mass spectrometry. This powerful method can be applied to measure other skin proteins and lipids collected by tape stripping. Here, for the first time, we apply this technique to investigate the epidermal kinetics of psoriasis, the first step in defining a kinetic profile for normal skin versus activated or quiescent psoriatic skin.MethodsPsoriatic subjects were given 2H2O orally as twice-daily doses for 16–38 days. Affected and unaffected skin was sampled by tape stripping and washing (modified Pachtman method). Proteins were isolated from the tape strips by a method that enriches for keratin. Turnover times were determined by gas chromatography/mass spectrometry. Kinetic data were compared to transepidermal water loss (TEWL).ResultsDeuterium-labeled protein from lesional psoriatic skin appeared at the skin surface within 3–8 days of label administration, whereas labeled protein from non-lesional skin requires 10–20 days to appear. Psoriatic skin had similar rate of growth despite varying anatomic location. Proteins recovered from tape strips were identified by nanoscale liquid chromatography/tandem mass spectrometry. Isolated peptides were >98% from keratin in uninvolved skin and >72% keratin in psoriatic skin. Revealing that one-quarter of all newly synthesized proteins in psoriatic skin are antimicrobial defense and other immune-related proteins. TEWL values were greater in lesional than non-lesional skin, suggesting barrier compromise in psoriatic skin despite increased clinical thickness.ConclusionsThis simple, elegant, and non-invasive method for measuring epidermal protein synthesis, which can also be adapted to measure epidermal lipids, provides a metric that may reveal new insights into the mechanisms and dynamic processes underlying psoriasis and may also provide an objective scale for determining response to therapeutic agents in pre-clinical and clinical trials. This opens a pathway to the non-invasive study of kinetics of protein formation in psoriasis or other skin diseases.
Highlights
Previous studies of epidermal kinetics in psoriasis have relied on invasive biopsy procedures or the use of radioactive labels
We have previously developed methods to measure the kinetics of keratin [3,4], triglycerides, fatty acids and cholesterol [5] using heavy water in human tissue and have measured kinetics of complex lipids from brain myelin [6]
Psoriasis is considered a systemic disease, these results indicate that the kinetics of uninvolved skin in psoriasis patients were comparable to normal skin and did not exhibit an increased basal turnover rate
Summary
Previous studies of epidermal kinetics in psoriasis have relied on invasive biopsy procedures or the use of radioactive labels. We previously developed a non-invasive method for measuring keratin synthesis in human skin using deuterated water labeling, serial collection of tape strips and measurement of deuterium enrichment in protein by mass spectrometry. This powerful method can be applied to measure other skin proteins and lipids collected by tape stripping. Abnormal epidermal turnover can impair skin barrier function and tissue repair; keratinocyte or keratin turnover may be critical in disorders of the skin as well as in response to therapy [1]. Skin lipid content is critical for maintaining skin barrier function and regulating water loss. There may be significant changes in lipid kinetics in psoriatic individuals reflecting this defect in lipid homeostasis
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