126 The selective serotonin reuptake inhibitor fluoxetine exerts anti-inflammatory actions on human epidermal keratinocytes

Abstract

A neonatal boy presented with ichthyosiform erythroderma, hypotrichosis, recurrent sepsis and skin infections, failure to thrive, constant vomiting and brain abnormalities. He had persistent thrombocytosis, hypoalbunemia and hypernatremia. IgE levels rose at age 0.6 years (985 kU/l) without eosinophilia. Cow milk allergy was diagnosed at 0.7 years. IVIG treatment from 0.6 years reduced infections and acitretin from age 0.7 years reduced scaling. Skin biopsy showed a psoriformic reaction with normal LEKTI but absent filaggrin staining. Vast immunological and metabolic analyses and ichtyosis and immunodeficiency gene panels were normal. Whole exome sequencing showed a heterozygous Desmoplakin missense variant c. 1756C>T, p.(His586Tyr). A heterozygous mutation in the neighboring nucleotide c.1757C>T, p.(His586Pro) with a similar phenotype was reported in one patient. The phenotype is typical for severe dermatitis, multiple allergies and metabolic wasting (SAM) syndrome to date reported in five other patients with homozygous Desmoglein 1 mutations. Desmoplakins and desmogleins are key molecules in desmosomes, which are adhesive intercellular junctions crucial in tissues prone to mechanical stress (e.g. skin, heart, gastrointestinal mucosa). Desmosomal proteins play a role in cell signalling and skin barrier function. Reported SAM patients developed dermatitis and erythroderma neonatally with failure to thrive (86%, 6/7), recurrent infections (86%, 6/7), elevated IgE (86%, 6/7), hypotrichosis (71%, 5/7), food allergy (71%, 5/7), developmental delay (71%, 5/7), variable gastrointestinal features (57%, 4/7), hypoalbuminemia (57%, 4/7) and hyper-/hyponatremia (43%, 3/7). The SAM syndrome is clinically similar to Netherton syndrome caused by SPINK5 mutations leading to a severe epidermal barrier defect. Desmoplakin mutations should be included in the differential diagnosis of erythrodermic, allergy and infection prone infants with skin barrier defects. 125Characterization of TSG-6 protein in healthy and inflammatory models of reconstructed human epidermis C Evrard, E De Vuyst, E Faway, C Lambert de Rouvroit, B Flamion and Y Poumay University of Namur, Namur, Belgium TSG-6 is an anti-inflammatory hyaluronan-binding protein involved in extracellular matrix remodelling whose functions have never been studied in skin. Characterization of TSG-6 was carried out in vivo in healthy human epidermis and in vitro using keratinocyte monolayers and reconstructed human epidermis (RHE). Distribution of TSG-6 protein was highlighted by immunofluorescence and levels of relative mRNA and protein expression were respectively measured by RT-qPCR and ELISA. The immunofluorescent signal of TSG-6 protein was located in the living layers of epidermis in vivo and in vitro, mostly in basal keratinocytes, and was restricted to the intracellular compartment. Because the localization of hyaluronan (HA) is in the extracellular matrix, no colocalization of TSG-6 and HA could thus be detected. ELISA assay shows that TSG-6 is abundant in the intracellula...