IMMUNOHISTOCHEMICAL ANALYSIS OF THE SKIN IN JUNCTIONAL EPIDERMOLYSIS-BULLOSA USING LAMININ-5 CHAIN SPECIFIC ANTIBODIES IS OF LIMITED VALUE IN PREDICTING THE UNDERLYING GENE MUTATION

The anchoring filament protein laminin 5 is composed of three polypept ide chains (alpha 3, beta 3 and gamma 2) each encoded by separate gene s (LAMA3, LAMB3 and LAMC2, respectively). Mutations in any of these th ree genes may give rise to the autosomal recessive blistering skin dis ease, junctional epidermolysis bullosa, At present, there is no easy w ay of predicting which of these three genes might harbour the pathogen etic laminin 5 mutations in a case of junctional epidermolysis bullosa . In this study, we assessed whether immunohistochemistry might be hel pful in this regard. We performed immunohistochemical labelling of the dermal-epidermal junction using alpha 3, beta 3 and gamma 2 chain-spe cific antibodies in 11 patients with junctional epidermolysis bullosa, in whom the laminin 5 mutations had been previously delineated. Altho ugh, labelling for the laminin 5 chain bearing the mutations was atten uated or undetectable in all cases, a complete absence of labelling or a reduction in the staining intensity for the other two chains was al so seen in all cases. The results showed that immunohistochemical labe lling of the dermal-epidermal junction using alpha 3, beta 3 and gamma 2 chain-specific antibodies is not a specific indicator for which of the laminin 5 chain genes contains the pathogenetic mutations, and is therefore unreliable in screening for individual laminin 5 gene mutati ons in cases of junctional epidermolysis bullosa.