Cellular basis of secondary infections and impaired desquamation in certain inherited ichthyoses.
Abstract | IMPORTANCE: OBJECTIVE: DESIGN, SETTING, AND PARTICIPANTS: Samples from library material were taken from patients with HI, EI, NS, and other ichthyoses, but with a normal LB secretory system, and in healthy controls and were evaluated by electron microscopy and immunohistochemical analysis from July 1, 2010, through March 31, 2013. MAIN OUTCOME AND MEASURES: RESULTS: In healthy controls and patients with X-linked ichthyosis, neutral lipid storage disease with ichthyosis, and Gaucher disease, LB secretion is normal, and delivery of LB-derived proteins and LL-37 immunostaining persists high into the SC. In contrast, proteins loaded into nascent LBs and their delivery to the SC interstices decrease markedly in patients with HI, paralleled by reduced immunostaining for LL-37, HBD2, and KLK7 in the SC. In patients with EI, the cytoskeletal abnormality impairs the exocytosis of LB contents and thus results in decreased LL-37, HBD2, and KLK7 secretion, causing substantial entombment of these proteins within the corneocyte cytosol. Finally, in patients with NS, although abundant enzyme proteins loaded in parallel with accelerated LB production, LL-37 disappears, whereas KLK7 levels increase markedly in the SC. CONCLUSIONS AND RELEVANCE: Together, these results suggest that diverse abnormalities in the LB secretory system account for the increased risk of secondary infections and impaired desquamation in patients with HI, EI, and NS.
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Authors | Aegean Chan, Elena Godoy-Gijon, Almudena Nuno-Gonzalez, Debra Crumrine, Melanie Hupe, Eung-Ho Choi, Robert Gruber, Mary L Williams, Keith Choate, Philip H Fleckman, Peter M Elias |
Journal | JAMA dermatology
(JAMA Dermatol)
Vol. 151
Issue 3
Pg. 285-92
(Mar 2015)
ISSN: 2168-6084 [Electronic] United States |
PMID | 25565224
(Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, U.S. Gov't, Non-P.H.S.)
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Chemical References |
- Antimicrobial Cationic Peptides
- DEFB4A protein, human
- beta-Defensins
- KLK7 protein, human
- Kallikreins
- Cathelicidins
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Topics |
- Antimicrobial Cationic Peptides
(metabolism)
- Case-Control Studies
- Exocytosis
- Humans
- Ichthyosis
(complications, genetics, pathology)
- Immunohistochemistry
- Kallikreins
(metabolism)
- Microscopy, Electron
- Skin
(pathology)
- Skin Diseases, Infectious
(etiology, pathology)
- beta-Defensins
(metabolism)
- Cathelicidins
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