230‐kDa and 190‐kDa proteins in addition to desmoglein 1 as immunological targets in a subset of pemphigus foliaceus with a combined cell‐surface and basement membrane zone immune staining pattern

Abstract

Pemphigus erythematosus, initially described as a combination of pemphigus with lupus erythematosus, and pemphigus foliaceus are now frequently considered localized and generalized variants of superficial pemphigus. Yet diagnostic criteria for pemphigus erythematosus remain controversial. Distinct from pemphigus foliaceus, pemphigus erythematosus displays immune depositions at the dermal-epidermal junction, which suggests additional immunopathological mechanisms. We present three patients with clinical and histopathologic signs of superficial pemphigus, who all exhibited an immunomorphology characteristic of pemphigus erythematosus. Complement depositions in a granular-linear fashion were consistently found at the dermal-epidermal junction besides in vivo bound and circulating antikeratinocyte cell-surface autoantibodies. Histopathology showed subcorneal acantholysis, and all sera contained antidesmoglein 1 but not antidesmoglein 3 autoantibodies detected by enzyme-linked immunosorbent assays (ELISA). Additional autoantibodies against a 230-kDa protein and against a 190-kDa protein comigrating with bullous pemphigoid antigen 1 (BP230) and periplakin, respectively, were present in all the patients' sera. As two sera specifically reacted with BP230 by ELISA, the presence of BP230-specific autoantibodies could be associated with dermal-epidermal immune staining in these patients. In pemphigus erythematosus, dermal-epidermal immune staining is generally attributed to the deposition of immune complexes, while the presence of BP230-specific autoantibodies has not been reported in this disease previously. Perhaps, the unique autoantibody profile of the patients in the study permits discrimination between patients with superficial pemphigus that display additional dermal-epidermal immune staining from those with conventional pemphigus foliaceus on a molecular basis. Further studies will be required to substantiate the frequency of this occurrence and to unravel its pathogenic significance.

IgA pemphigus – Occurrence of anti‐Desmocollin 1 and anti‐Desmoglein 1 antibody reactivity in an individual patient

“…Skin biopsy specimens were processed for routine histologic and immunomor‐phologic examinations [17]. Direct immunofluorescence microscopy using 6‐μm cryostat sections from perilesional skin and indirect immunofluorescence microscopy using rhesus monkey esophagus and normal human skin was performed according to standard procedures [17].…”

“…Skin biopsy specimens were processed for routine histologic and immunomor‐phologic examinations [17]. Direct immunofluorescence microscopy using 6‐μm cryostat sections from perilesional skin and indirect immunofluorescence microscopy using rhesus monkey esophagus and normal human skin was performed according to standard procedures [17]. Sodium dodecyl sulfate‐polyacry‐lamide gel (SDS‐PAGE) electrophoresis and immunoblotting of normal human epidermal and dermal extracts were performed as described previously [17].…”

“…Direct immunofluorescence microscopy using 6‐μm cryostat sections from perilesional skin and indirect immunofluorescence microscopy using rhesus monkey esophagus and normal human skin was performed according to standard procedures [17]. Sodium dodecyl sulfate‐polyacry‐lamide gel (SDS‐PAGE) electrophoresis and immunoblotting of normal human epidermal and dermal extracts were performed as described previously [17]. ELISA for IgG autoantibodies to Dsg1 and Dsg3 were performed using commercially available ELISA kits (MBL, Nagoya, Japan) following the manufacturer's instructions [17].…”

“…Sodium dodecyl sulfate‐polyacry‐lamide gel (SDS‐PAGE) electrophoresis and immunoblotting of normal human epidermal and dermal extracts were performed as described previously [17]. ELISA for IgG autoantibodies to Dsg1 and Dsg3 were performed using commercially available ELISA kits (MBL, Nagoya, Japan) following the manufacturer's instructions [17]. To detect IgA anti‐Dsg autoantibodies these ELISA kits were modified applying peroxidase‐conjugated rabbit anti‐human IgA and peroxidase‐conjugated rabbit anti‐human IgG/IgA/IgM/kappa/lambda as second step antibodies, respectively (Dako, Colorado, USA).…”

Internalization of Non-Clustered Desmoglein 1 without Depletion of Desmoglein 1 from Adhesion Complexes in An Experimental Model of the Autoimmune Disease Pemphigus Foliaceus

“…Subcorneal acantholysis is a common finding of both PF and its localized form, pemphigus erythemathosus (PE); nevertheless, some aspects of PE immunopathology, including immune depositions along the basement membrane zone, differentiate this abortive variant from generalized PF (11)(12). For this reason, and also to reproduce physiological conditions, cellular responses were triggered by using whole sera.…”