Genetic Linkage Between the Collagen Type VII Gene COL7A1 and Pretibial Epidermolysis Bullosa with Lichenoid Features

Pretibial epidermolysis bullosa is a rare form of dominant dystrophic epidermolysis bullosa. The disease was diagnosed after considerable delay in a large Belgian family and was remarkable for its late age at onset and its misleading clinical presentation in the proband, which strongly resembled keratosis lichenoides chronica. Both recessively and dominantly inherited forms of dystrophic epidermolysis bullosa have been shown to be linked to the collagen type VII gene, COL7A1. Two-point linkage analysis with two intragenic polymorphisms (PvuII, AluI) in COL7A1 was performed. Strong genetic linkage between the disease in this family and COL7AI was demonstrated by a lod score of 44.5 (theta = 0) for the AluI polymorphism. The observed intrafamilial variability of clinical phenotypes contradicts the presently proposed classification of dominantly inherited dystrophic epidermolysis bullosa

Expression of the chemokine receptor CCR5 in psoriasis and results of a randomized placebo controlled trial with a CCR5 inhibitor

Several reports have indicated that the chemokine receptor CCR5 and its ligands, especially CCL5 (formerly known as RANTES), may play a role in the pathogenesis of psoriasis. The purpose of this investigation was to examine the expression of CCR5 and its ligands in chronic plaque psoriasis and to evaluate the clinical and immunohistochemical effect of a CCR5 receptor inhibitor. Immunohistochemical analysis showed low but significant increased total numbers of CCR5 positive cells in epidermis and dermis of lesional skin in comparison to non-lesional skin. However, relative expression of CCR5 proportional to the cells observed revealed that the difference between lesional and non-lesional skin was only statistically significant in the epidermis for CD3 positive cells and in the dermis for CD68 positive cells. Quantification of mRNA by reverse transcriptase-polymerase chain reaction only showed an increased expression of CCL5 (RANTES) in lesional skin. A randomized placebo-controlled clinical trial in 32 psoriasis patients revealed no significant clinical effect and no changes at the immunohistochemical level comparing patients treated with placebo or a CCR5 inhibitor SCH351125. We conclude that although CCR5 expression is increased in psoriatic lesions, this receptor does not play a crucial role in the pathogenesis of psoriasis