ABSTRACT
Desmogleins (Dsgs), cadherin-type cell adhesion molecules, are targeted in skin-blistering diseases such as pemphigus and staphylococcal scalded skin syndrome (SSSS). The role of Dsg4, a new isoform, was investigated in these diseases. Dsg4 was recognized by 30 (77%) of 39 pemphigus sera containing anti-Dsg1 IgG but not by 16 pemphigus sera containing no anti-Dsg1 IgG or by 34 normal control sera. The Dsg4 immunoreactivity of these sera was abolished by removal of anti-Dsg1 IgG. Conversely, the removal of anti-Dsg4 IgG from pemphigus sera reduced the immunoreactivity against Dsg1 only 13.8% +/- 8.8% (n = 23) and did not affect its ability to induce blisters in neonatal mice. IgG that was affinity-purified on Dsg4 recognized Dsg1 but failed to induce blisters, while IgG purified on Dsg1 from the same pemphigus foliaceus sera induced blisters. Thus, pemphigus sera show Dsg4 reactivity due to cross-reactivity of a subset of anti-Dsg1 IgG, and the Dsg4/Dsg1-cross-reacting IgG has no demonstrable pathogenic effect. In addition, Dsg4 was not cleaved by exfoliative toxins that induce blisters in SSSS. These findings suggest that Dsg4 may play a role other than adhesion and that the cross-reactivity of desmoglein autoantibodies should be factored into the framework of future studies of autoimmune mechanisms in pemphigus.
Subject(s)
Cadherins/physiology , Cytoskeletal Proteins/physiology , Pemphigus/immunology , Staphylococcal Scalded Skin Syndrome/immunology , Amino Acid Sequence , Animals , Animals, Newborn , Autoantibodies/immunology , Cadherins/immunology , Conserved Sequence , Cricetinae , Cross Reactions , Cytoskeletal Proteins/immunology , Desmogleins , Desmosomes/immunology , Epidermis/metabolism , Humans , Immunoglobulin G/immunology , Immunoglobulin G/isolation & purification , Mice , Mice, Inbred ICR , Molecular Sequence Data , Pemphigus/blood , Pemphigus/pathology , Recombinant Fusion Proteins/chemistry , Recombinant Fusion Proteins/immunology , Sequence Homology, Amino Acid , Staphylococcal Scalded Skin Syndrome/blood , Staphylococcal Scalded Skin Syndrome/pathologyABSTRACT
In order to study the differences between staphylococcal scalded skin syndrome (SSSS) and bullous impetigo, the anti exfoliatin level was assessed in the sera from both groups of patients, and no significant difference in the level was found. However a significant difference was noted in the anti alpha-toxin levels in sera from both group of patients; that of SSSS patients was much lower than that of impetigo patients and of children in a control group. Five out of 6 patients with SSSS showed an unchaged level of anti alpha-toxin at the second examination, while an increased anti exfoliatin level was noted in 4 out of 6 SSSS patients.
