Naslov
Sphingolipids in atopic dermatitis

Autori
Jakasa I, Jurakic Toncic R, McAleer MA, Irvine AD, Kezic S

Vrsta, podvrsta i kategorija rada
Sažeci sa skupova, sažetak, znanstveni

Skup
EAACI SUMMER SYMPOSIUM ON EPITHELIAL BARRIERS AND MICROBIOME

Mjesto i datum
Davos, Švicarska, 28-30.07.2022

Vrsta sudjelovanja
Poster

Vrsta recenzije
Međunarodna recenzija

Ključne riječi
sphingolipids, atopic dermatitis, skin barrier, GBA

Sažetak
Dysfunctional skin barrier plays a key role in the pathophysiology of atopic dermatitis (AD), a common inflammatory skin disease. Altered composition of ceramides is regarded as a major cause of skin barrier dysfunction, however it is not clear whether these changes are intrinsic or initiated by inflammation and aberrant immune response in AD. In our study we investigated the levels of free sphingoid bases (SBs) of different chain length and their ceramides (CER) and glucosylceramide (GlcCER) in the stratum corneum (SC) of adult AD patients and healthy controls and related them to skin barrier function, disease severity and local cytokine milieu. The results demonstrated difference in the levels of SBs as well as their ceramides and GlcCER between healthy and AD skin. The alterations in the investigated lipid markers were more prominent in lesional skin, and that their levels were strongly associated with skin barrier function, disease severity and SC cytokine concentrations. The second study, performed in a cohort of children with AD focused on the activity of epidermal β-glucocerebrosidase (GBA), an important enzyme for biosynthesis of CER in the SC. Next to the GBA activity, we measured the SC levels of GBA substrate (GlcCER) and enzymatic product (Glucosylcholesterol, GlcCHOL). These lipid biomarkers were measured before and after local corticosteroid therapy. This study showed that SC of patients with AD has increased GBA activity. Consistently, increased GBA activity is paralleled by elevated levels of GlcChol. Activity of GBA activity and levels of GlcChol correlated strongly with skin barrier function and levels of multiple cytokines, especially interleukin-1α and interleukin-18. Local anti-inflammatory therapy corrected increased GBA activity and GlcChol levels. Taken together, our studies demonstrate a broad range of lipid abnormalities in AD and important role of immune/inflammatory response in metabolism of ceramides in AD.

Izvorni jezik
Engleski

Znanstvena područja
Kemija, Temeljne medicinske znanosti

POVEZANOST RADA