Ethnic endotypes in paediatric atopic dermatitis depend on immunotype, lipid composition and microbiota of the skin.

BACKGROUND: Atopic dermatitis (AD) endotypes differ with ethnicity. We examined the skin microbiota, cytokine and lipid profiles in Greenlandic Inuit and Danish children with AD. METHODS: Twenty-five Inuit children with AD and 25 Inuit control children were clinically examined and compared to previously collected data from 25 Danish children with AD. Skin tape strips and skin swabs were collected from lesional and non-lesional skin. Levels of cutaneous immune biomarkers, free sphingoid bases and their (glycosyl)ceramides were analysed. Skin swabs were analysed with 16S rRNA and tuf gene for characterization of bacterial species communities. RESULTS: Bacterial ß-diversity was significantly different between Inuit and Danish AD skin, in both lesional (p < 0.001) and non-lesional (p < 0.001) AD skin, and there was a higher relative abundance of Staphylococcus aureus in Danish compared to Inuit lesional (53% vs. 8%, p < 0.01) and non-lesional skin (55% vs. 5%, p < 0.001). Danish AD children had a higher α-diversity than Inuit children in non-lesional (p < 0.05) but not in lesional skin. Significantly higher levels of type 2 immunity cytokine interleukin (IL)-4 (p < 0.05) and IL-5 (p < 0.01) were identified in Inuit compared to Danish AD children. In contrast, IL-33 (p < 0.01) was higher in Danish lesional and non-lesional AD skin. Higher levels of long-chain glucosylceramide (GlcCER)[S](d26:1) were found in lesional (p < 0.001) and non-lesional (p < 0.001) Inuit skin compared with Danish AD skin. NMF levels were similar in Inuit and Danish AD skin. CONCLUSION: Skin microbiota, cytokine and lipid composition differed significantly between Inuit and Danish children with AD and showed a stronger type 2 immune signature in Inuit children.

Identification of a novel acidic mammalian chitinase distinct from chitotriosidase.

Chitinases are ubiquitous chitin-fragmenting hydrolases. Recently we discovered the first human chitinase, named chitotriosidase, that is specifically expressed by phagocytes. We here report the identification, purification, and subsequent cloning of a second mammalian chitinase. This enzyme is characterized by an acidic isoelectric point and therefore named acidic mammalian chitinase (AMCase). In rodents and man the enzyme is relatively abundant in the gastrointestinal tract and is found to a lesser extent in the lung. Like chitotriosidase, AMCase is synthesized as a 50-kDa protein containing a 39-kDa N-terminal catalytic domain, a hinge region, and a C-terminal chitin-binding domain. In contrast to chitotriosidase, the enzyme is extremely acid stable and shows a distinct second pH optimum around pH 2. AMCase is capable of cleaving artificial chitin-like substrates as well as crab shell chitin and chitin as present in the fungal cell wall. Our study has revealed the existence of a chitinolytic enzyme in the gastrointestinal tract and lung that may play a role in digestion and/or defense.