Podium Presentation in Room 2 on Wednesday at 11:40 (Chair: Elizabeth Want)
Authors: Evgeny Berdyshev, Irina Bronova, Elena Goleva, and Donald YM Leung
INTRODUCTION: Skin tape stripping (STS) methodology offers a possibility to look non-invasively at the components of the top skin layer called stratum corneum. In spite of its rising popularity, STS methodology has limited clinical applicability due to its intrinsic difficulties in linking classical lipidomics or metabolomics with the need for absolute normalized quantitation of analytes. Major obstacles are the need to remove acrylamide glue from the sample and the need to normalize mass spectrometric data as material content per STS varies substantially between individuals as well as between layers of the skin. Recently, the demand by clinical studies focusing at atopic skin diseases resulted in the development by us of an approach that allows removal of stratum corneum material from D-Squame™ STS and processing in a way that permits the LC-MS/MS analysis of lipids and polar components with parallel measurement of protein content in the same sample from just two STS.
OBJECTIVES AND METHODS: The developed approach was applied to several clinical trials to gain insight into the mechanisms leading to the shift in fatty acid length in skin lipids in adult subjects with atopic dermatitis (AD) and to see if STS metabolomics/lipidomics can identify AD endotypes.
RESULTS: We found that AD-linked hyperactivation of type 2 immune response leads to the inhibition of expression of skin fatty acid elongases ELOVL3 and ELOVL6 with a concomitant increase in the expression of ELOVL1 and ELOVL4 that altogether results in reduced synthesis of very long-chain fatty acids and accumulation of short-chain fatty acids. Importantly, those changes are identifiable not only in the lesional but also in normal looking non-lesional skin. This knowledge is now being used to characterize lipidomic outcomes of IL4/IL13-receptor inhibition in moderate to severe AD patients with biologic (Dupilumab™) in a large NIH-guided clinical trial. Next, our methodology was instrumental in characterizing children with AD and food allergy to peanut as a separate AD endotype based in part on stratum corneum content of components of natural moisturizing factor urocanic acid (UCA), pyroglutamic acid (PCA), and the ceramide absolute amounts as well as ceramide species composition. Additional mass spectrometric work focused at children with allergy to peanut but not having AD identified them as additional unique endotype.
CONCLUSIONS: Targeted LC-MS/MS analysis of non-lesional stratum corneum components separates food allergy only, AD with food allergy, and AD only subjects into separate subphenotypes. As the so-called “atopic march” is thought to be initiated by the loss of skin barrier function and allergen penetration through the skin in early childhood, it is possible that mass spectrometric STS analysis early in life can identify children at risk of developing AD and food allergy. Several NIH-guided clinical trials are in preparation to answer this question.
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