Monocytes form a significant component of the inflammatory reaction taking place in the skin of atopic dermatitis and psoriasis. Chemokines are pivotal in mediating the attraction of leucocytes to sites of inflammation. The CC-chemokine, monocyte chemotactic protein 1 (MCP-1/CCL2), is expressed by keratinocytes in both atopic dermatitis and psoriasis. MCP-1 binds to the chemokine receptor CCR2 which is known to be expressed on monocytes and macrophages. We examined the expression of CCR2 on peripheral blood monocytes from patients with psoriasis (n=8) and atopic dermatitis (n=7) and found it to be expressed on approximately 90% of the cells, whereas monocytes from healthy donors had a significantly lower CCR2 expression (p<0.05). Skin biopsies from patients suffering from atopic dermatitis and psoriasis revealed that CCR2-positive cells expressed CD163, a marker for monocytes/macrophages. However, not all CD163-positive cells expressed CCR2, which could be interpreted as a mechanism for retaining the macrophages in the skin. Furthermore, we found that keratinocytes are able to express MCP-1, when stimulated with tumour necrosis factor-alpha and/or interferon-gamma in a dose-dependent manner. Thus MCP-1 and CCR2 interaction is likely of importance for the monocyte/macrophage trafficking of inflammatory skin disorders.

Desmoglein 3 (Dsg3), encoded by DSG3 gene, is the major component of desmosomes which contribute to cell-cell adhesion in epidermis. Dsg3-deficient mice show erosions in the mucosa and hypotrichosis, caused by loss of cell-cell adhesion. Autoantibodies against human Dsg3, called as mucosal pemphigus vulgaris, lead to suprabasal acantholysis histologically and blister formation limited to the mucosa clinically. A patient with Dsg3 deficiency, however, has never been reported. A 1 year-old female baby presented with recurrent erosions in the oral and laryngeal mucosa after birth. Her conjunctival and genital mucosa is spared and her hair was normally growing. Histological examination of skin biopsy showed suprabasal acantholytic blisters, but direct and indirect immunofluorescences were negative. Whole genome sequencing from her DNA identified a novel homozygous nonsense mutation in desmoglein 3. Using direct sequencing and restriction fragment length polymorphism assays, we found that her parents harbor the heterozygous mutations in DSG3. Immunofluorescence and immunoblotting showed that Dsg3 was not observed in keratinocytes from her skin as well as oral mucosa. Electron microscopy of her skin biopsy shows mature desmosomes in the basal layer. In conclusion, we describe a new hereditary disease featuring recurrent mucosal erosions caused by homozygous mutation in DSG3. 740 Chromosomal microarray analysis for the molecular diagnosis of nevoid basal cell carcinoma syndrome and X-linked ichthyosis