While the transition from basic life science research to clinical applications is often much more cumbersome than promised, Gosty nski et al. took the opposite approach and demonstrated how a scholarly, biology-guided perspective on human skin disease can reveal basic principles of human biology. Hereditary blistering diseases represent not only a disastrous fate for affected patients, but also an opportunity for understanding human molecular physiology and pathophysiology. On the basis of their clinical expertise, Gosty nski et al. have elegantly used differences between lesional and non-lesional as a unique opportunity to dissect the role of structural skin proteinsnamely type XVII collagen, laminin b3 and type VII collagen -in melanocyte biology, thus elucidating a new concept in melanocyte biology by transferring knowledge in reverse direction from bedside to bench.Key words: bullous pemphigoid -melanocyte -melanoma -skin -type XVII collagen
Accepted for publication 16 June 2014In the study presented by Gosty nski et al.(1), the clinical skin phenotype of patients with three different gene defects of structural proteins of the skin were compared: type XVII collagen, type VII collagen and laminin b3 (part of laminin 332). Intriguingly, patients with these gene defects were found to have healthy patches in the midst of a fragile, erosive and blistering skin. In these patches, the genetic defects were repaired or inactivated, leading to a phenomenon termed revertant mosaicism (2). On the basis of their long-standing experience with the management of patient with hereditary blistering dermatoses (3,4), the authors made a simple, but striking observation: they found hyperpigmentations in revertant skin of patients with non-Herlitz type junctional epidermolysis bullosa, bearing a defect in type XVII collagen, while the affected skin showed reduced or no pigmentation.Interestingly, reversion of type VII collagen or laminin b3 in keratinocytes did not influence the pigmentation. With type VII collagen, the melanocyte density was equal to healthy skin, indicating that this molecule is not relevant for melanocyte proliferation and homeostasis. In contrast, laminin b3 defects led to a reduced melanocyte density, which was not improved in revertant skin patches (1). The clue here might be that the laminin b3 expressed by melanocytes is essential for their proliferation, survival and organization. As the authors explain, the gene defect is not repaired in melanocytes residing in revertant skin patches. This invites the conclusion that it is only type XVII collagen which connects keratinocytes and melanocytes (1).If we contemplate on this further, the question arises whether melanocytes also have the ability to correct their genetic defect and whether they exist in patients with laminin b3 defects? If so, what will be the clinical presentation of revertant melanocytes? Do they appear as atypical naevi? Several clinical reports describe atypical melanocytic naevi in patients with epidermolysis bullosa, which are ...
