Characterization of the changes in matrix molecules at the dermoepidermal junction in lupus erythematosus

Abstract

Electron microscopy has revealed that the deposition of immunoglobulin in the skin of lupus erythematosus (LE) patients occurs on and below the basal lamina of the basement membrane (BM). The composition of the BM is now to some extent known, and antibodies have been developed against several of its individual components. In this study, we attempt to elucidate the status of some matrix molecules in the dermoepidermal junction in LE. Lesional and nonlesional skin from LE patients was examined using immunofluoresence microscopy with monoclonal and polyclonal antibodies against 6 matrix molecules. Immunoelectron microscopy using monoclonal antibodies was used to discern changes in type IV and type VII collagen. By immunofluorescence microscopy, type IV collagen, type VII collagen, and fibronectin were altered in lesional skin. There was a statistically significant correlation between the presence of immunoglobulin and alteration of type IV collagen and type VII collagen in lesional skin. The alterations in type IV and type VII collagens were confirmed on immune‐electron microscopy which showed fragmentation of staining of both antigenic components, particularly type IV collagen.

Granzyme B is elevated in autoimmune blistering diseases and cleaves key anchoring proteins of the dermal-epidermal junction

“…Mooney et al . have previously shown fragmented collagen VII in the DEJ of patients with discoid lupus erythematosus 22 . While normal skin displayed a continuous, strong staining for collagen VII lining the interface between epidermis and dermis (Fig.…”

Matrix metalloproteinases as mediators of tissue injury in different forms of cutaneous lupus erythematosus

“…Collagen types IV and VII are fragmented and disrupted in lesional LE skin, and changes in fibronectin have been reported 34 . In fact, MMP‐3 degrades collagens IV, VII and fibronectin at least in vitro , while MMP‐7, ‐10 and ‐26 cleave collagen IV and fibronectin 32 .…”

“…24,27,31,33 Collagen types IV and VII are fragmented and disrupted in lesional LE skin, and changes in fibronectin have been reported. 34 In fact, MMP-3 degrades collagens IV, VII and fibronectin at least in vitro, while MMP-7, -10 and -26 cleave collagen IV and fibronectin. 32 Thus, we cannot rule out the contribution of some of these MMPs to basement membrane changes observed in lupus.…”

Dermatopathologic Manifestations of Rheumatologic Diseases

“…They appear to damage type IV and VII collagens. 29,30 Approximately 60% of SCLE lesional skin biopsies have a positive lupus band test displaying deposits of IgM, IgG and IgA. A particular pattern of "dust-like particles" of IgG in and around the epidermal basal keratinocytes and subepidermal regions has been described in SCLE patients.…”