Jeroen van Smeden, Michelle Janssens, Walter A

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Presentation transcript:

Intercellular Skin Barrier Lipid Composition and Organization in Netherton Syndrome Patients  Jeroen van Smeden, Michelle Janssens, Walter A. Boiten, Vincent van Drongelen, Laetitia Furio, Rob J. Vreeken, Alain Hovnanian, Joke A. Bouwstra  Journal of Investigative Dermatology  Volume 134, Issue 5, Pages 1238-1245 (May 2014) DOI: 10.1038/jid.2013.517 Copyright © 2014 The Society for Investigative Dermatology, Inc Terms and Conditions

Figure 1 Relative chain length distribution of stratum corneum (SC) free fatty acids (FFAs). (a, b) Present bar graphs showing the relative abundance of, respectively, saturated FFAs and monounsaturated fatty acids (MUFAs). The total abundance of saturated FFAs and MUFAs together was set to 100%. Controls (n=5) and Netherton syndrome (NTS) patients (n=8) are presented as gray and black bars, respectively. Error bars represent SD values; ND means ‘not detected’. No odd chain length MUFAs were detected from either NTS or controls. The large SD of the NTS patients are caused by intersubject variation and are not due to methodological variation. Journal of Investigative Dermatology 2014 134, 1238-1245DOI: (10.1038/jid.2013.517) Copyright © 2014 The Society for Investigative Dermatology, Inc Terms and Conditions

Figure 2 Three-dimensional (3D) ion chromatograms showing all stratum corneum (SC) ceramide (CER) subclasses and chain lengths. (a) Control SC and (b, c) Netherton syndrome (NTS) patients. Retention time (3.6–8.3min), mass (480–1200a.m.u.), and relative intensity of each peak are shown on the x, y, and z axis, respectively. Chromatograms are normalized to their most abundant peak. The chromatograms of the NTS patients show a decreased chain length of the CERs. In addition, in c there is a decrease in acyl-CERs ([EO] CERs) and a narrower distribution of total number of carbons in all other CER subclasses. NTS patients also show an increase in short-chain CERs, in particular CERs with a chain length of 34 carbon atoms (C34 CERs), which are indicated in the chromatograms by red peaks. The 3D ion chromatograms of all controls and NTS patients are listed in Supplementary Figure S5 online. Journal of Investigative Dermatology 2014 134, 1238-1245DOI: (10.1038/jid.2013.517) Copyright © 2014 The Society for Investigative Dermatology, Inc Terms and Conditions

Figure 3 Relative abundance of specific ceramides (CERs). Dot plots showing the relative abundance of (a) CERs, (b) short-chain CERs (C32-C38), and (c) the ratio of acyl-glucosylceramides (GlcCERs)/acyl-CERs. Black horizontal lines and the corresponding values indicate mean values (±SD). Gray dotted lines indicate averages for two different cohorts observed: five Netherton syndrome (NTS) patients with normal acyl-CER levels and three NTS patients with reduced acyl-CER levels. Individual NTS patients are labeled ①–⑧. Journal of Investigative Dermatology 2014 134, 1238-1245DOI: (10.1038/jid.2013.517) Copyright © 2014 The Society for Investigative Dermatology, Inc Terms and Conditions

Figure 4 Small angle X-ray diffraction (SAXD) patterns. (a) Controls and (b, c) Netherton syndrome (NTS) patients. The positions of the peaks (q) are indicative for the periodicity of the lipid lamellae (illustrated by the inset in the upper right corner of a. Panel b shows NTS patients with a normal level of acyl-ceramides (CERs), whereas panel c presents diffraction patterns of NTS patients with a reduced level of acyl-CERs. From the scattering angle, the scattering vector (q) was calculated by q=4π sinθ/λ, in which λ is the wavelength of the X-rays at the sample position and θ is the scattering angle. Individual NTS patients are labeled ①–⑧. Journal of Investigative Dermatology 2014 134, 1238-1245DOI: (10.1038/jid.2013.517) Copyright © 2014 The Society for Investigative Dermatology, Inc Terms and Conditions

Figure 5 CH2 symmetric stretching peak position in stratum corneum (SC) of controls (gray dots) and Netherton syndrome (NTS) patients (black dots). A higher peak position indicates a higher degree of conformational disordering of the lipid chains. Individual NTS patients are labeled ①–⑧. Journal of Investigative Dermatology 2014 134, 1238-1245DOI: (10.1038/jid.2013.517) Copyright © 2014 The Society for Investigative Dermatology, Inc Terms and Conditions

Figure 6 Immunofluorescent staining of skin sections of a control and two Netherton syndrome (NTS) patients. The highlighted area in the control is magnified for better visualization of the epidermis. All images were taken at original magnification × 20 and the scale bar = 100μm. Journal of Investigative Dermatology 2014 134, 1238-1245DOI: (10.1038/jid.2013.517) Copyright © 2014 The Society for Investigative Dermatology, Inc Terms and Conditions