A subset of pemphigus foliaceus patients exhibits pathogenic autoantibodies against both desmoglein-1 and desmoglein-3.
In pemphigus vulgaris the major pathogenic antibody binds desmoglein-3, and mediates mucosal disease. Development of cutaneous disease is associated with acquisition of antibodies to desmoglein-1. In pemphigus foliaceus, and its endemic form, fogo selvagem by contrast, the major pathogenic antibody recognizes desmoglein-1 and mediates cutaneous disease only. In this study, we sought to determine the prevalence of antibodies to desmoglein-3 in patients with pemphigus foliaceus and fogo selvagem. We produced recombinant desmoglein-1 and desmoglein-3, and used them in highly sensitive and specific enzyme-linked immunosorbent assays, as well as immunoprecipitation assays. We detected antibodies to desmoglein-3 in 19 of 276 patients with pemphigus foliaceus and fogo selvagem, who had cutaneous disease only. We showed that these antibodies to desmoglein-3 could be absorbed in a concentration-dependent manner by desmoglein-3 but not by desmoglein-1. Also antibodies to desmoglein-1 could be absorbed in a concentration-dependent manner by desmoglein-1 but not desmoglein-3. This suggests that two separate species of antibody are present rather than one antibody capable of cross-reacting with both desmoglein-1 and desmoglein-3. Finally, it was shown that affinity-purified antibodies to desmoglein-3 from patients with pemphigus foliaceus and fogo selvagem induced a pemphigus vulgaris-like skin disease in mice by passive transfer. These results suggest that a subset of patients with pemphigus foliaceus and fogo selvagem have antibodies to desmoglein-3 that may be involved in the pathogenesis of their cutaneous disease.
Arteaga
Luis A
LA
Department of Dermatology, University of North Carolina at Chapel Hill, 27599, USA.
Prisayanh
Philip S
PS
Warren
Simon J P
SJ
Liu
Zhi
Z
Diaz
Luis A
LA
Lin
Mong-Shang
MS
D000818:Animals; D000831:Animals, Newborn; D001323:Autoantibodies / Q000097:blood* / Q000494:pharmacology; D015820:Cadherins / Q000276:immunology*; D051183:Desmoglein 1; D051184:Desmoglein 3; D004797:Enzyme-Linked Immunosorbent Assay; D006801:Humans; D051379:Mice; D008807:Mice, Inbred BALB C; D010392:Pemphigus / Q000276:immunology*; D012680:Sensitivity and Specificity; D012867:Skin / Q000276:immunology
D001323:Autoantibodies; D015820:Cadherins; C071894:DSG3 protein, human; D051183:Desmoglein 1; D051184:Desmoglein 3