Anchoring fibrils, collagen VII, and neutral metalloproteases in recessive dystrophic epidermolysis bullosa inversa

Structure of the anchoring fibrils, expression of collagen VII, and gelatinolytic activity in skit fibroblasts were assessed in six patients with epidermolysis bullosa dystrophica (EBD) inversa and in control groups consisting of probands with other EBD subtypes and healthy individuals. Ali six patients with EBD inversa, as well as the patients with generalized ocalized EBD, showed positive staining with antibodies to collagen VII, the major anchoring fibril protein. Four patients with severe generalized mutilating EBD exhibited negative staining. Ultrastructurally, normal anchoring fibrils were demonstrable in uninvolved skin of patients with localized, inversa, and generalized non-multilating subtypes. At the same time, a and high degree of variability was observed in the amount and quality of anchoring fibrils in the various stages of lesional skin, including co-existence of normal and partially degraded anchoring fibrils. Of all 12 patients only one localized and two inversa cases showed an increased gelatinolytic activity in vitro. However, the high activity was associated with neither the severity of the disease nor the inversa subtype. In addition, intact collagen VII could be extracted from the dermis of one inversa patient. The present data show no correlation between increased in vitro geletinolytic activity and abnormalities of the anchoring fibrils or collagen VII in skin of patients with recessive EBD, and therefore suggest molecular heterogeneity of the causative pathogenetic mechanism.