Arch Dermatol Res (1991) 283:1-4 Archives of 9 Springer-Verlag 1991 Very late antigen (VLA) expression in various forms of epidermolysis bullosa simplex V. Nazzaro, E. Berti, R. Cavalli, A. Brusasco, and R. Caputo I. Clinica Dermatologica, University of Milan IRCCS, Ospedale Maggiore, Via Pace 9, 1-20122Milan, Italy ReceivedJune 16, 1990 Summary. The very late antigen (VLA) glycoproteins are a family of adhesion membrane receptors involved in cell- cell and cell-matrix interactions. In order to investigate the expression of these molecules in inherited epidermolysis bullosa (EB), we studied the reactivity of monoclonal anti- bodies directed against VLA-1, -2, -3, -4, -5, and -6, and VLAjO receptors in skin sections from patients affected by several types of EB simplex (EBs) using indirect immuno- fluorescence. Skin samples were obtained from six patients with generalized type (Koebner), one patient with localized type (Weber-Cockayne) and one patient with DoMing- Meara EBs type and also from two normal controls. No significant modification of the expression of these adhesion receptors was observed. Anti-VLA-2 and anti-VLA-3 stained the whole cytoplasmic membrane of basal kera- tinocytes and allowed the detection of focal areas of cytoly- sis in unblistered skin from the Koebner and DoMing- Meara type. In Koebner type blisters anti-VLA-3 stained the cell remnants at the roof of the blister with a linear staining along the epidermal basement membrane on the dermal side. In Dowling-Meara type blisters anti-VLA-3 also stained cell remnants at the bottom of the cavity. Anti- VLA-6 stained the bottom of the blister cavity with the same distribution of bullous pemphigoid serum but with a stronger and more constant reactivity. Our data show that anti:VLA-3 and anti-VLA-6 can usefully be utilized in diagnostic immunomapping studies of EBs. Key words: Epidermolysis bullosa simplex - Integrins - Very late antigens Epidermolysis bullosa simplex (EBs) represents a hetero- geneous group of inherited mechanobullous diseases in Offprint requests to. R. Caputo which blister formation takes place above the basement membrane zone. At least five types of EBs have been described including the generalized type (Koebner), the localized type (Weber-Cockayne), the EBs with mottled pigmentation, the Ogna type and the Dowling-Meara type [6, 7]. All the types are characterized ultrastruc- turally by an intraepidermal separation occurring by lysis of epidermal basal cells. In the Dowling-Meara type the basal cell cytolysis is accompanied by typical clumping of tonofilaments [1]. The pathogenesis of EBs is unknown although several mechanisms of blister formation have been postulated, such as the involvement of temperature- sensitive cytolytic enzymes or defective cytoskeletal or- ganization [15]. Recently, some monoclonal antibodies have been raised against a family of adhesion cell surface receptors known as integrins. The integrins are a set of heterodimeric receptors consisting of a common/~-chain and different e-chains that confer selective affinity toward extracellular matrix glycoproteins carrying the amino acid sequence Arg-Gly-Asp [2, 10, 13]. The VLA glyco- proteins are a subgroup of this important adhesion recep- tor family which comprises at least six heterodimers, mainly involved in cell binding with collagen (VLA-2, -3), laminin (VLA-3, -6), and fibronectin (VLA-3, -4, -5) [11, 14, 19-22]. The VLA receptors appear to be almost ubiquitous and at least three of them (VLA-2, -3, -6) have been identified on the cytoplasmic membrane of epidermal basal cells where they may play a role in kera- tinocyte cohesion and anchorage to the basement mem- brane [17]. We have questioned whether these com- ponents might be reduced or absent in various forms of inherited EB. In a previous study we investigated the VLA ex- pression in junctional and dystrophic EB [18]. In the present study we report on the expression of VLA cell surface receptors in various forms of EBs including the generalized type (Koebner), the localized type (Weber- Cockayne) and the Dowling-Meara type.