Antibodies against keratinocyte antigens other than desmogleins 1 and 3 can induce pemphigus vulgaris-like lesions.
Pemphigus is an autoimmune disease of skin adhesion associated with autoantibodies against a number of keratinocyte antigens, such as the adhesion molecules desmoglein (Dsg) 1 and 3 and acetylcholine receptors. The notion that anti-Dsg antibodies alone are responsible for blisters in patients with pemphigus vulgaris (PV) stems from the ability of rDsg1 and rDsg3 to absorb antibodies that cause PV-like skin blisters in neonatal mice. Here, we demonstrate that PV IgGs eluted from rDsg1-Ig-His and rDsg3-Ig-His show similar antigenic profiles, including the 38-, 43-, 115-, and 190-kDa keratinocyte proteins and a non-Dsg 3 130-kDa polypeptide present in keratinocytes from Dsg 3 knockout mouse. We injected into Dsg 3-lacking mice the PV IgGs that did not cross-react with the 160-kDa Dsg 1 or its 45-kDa immunoreactive fragment and that showed no reactivity with recombinant Dsg 1. We used both the Dsg3(null) mice with a targeted mutation of the Dsg3 gene and the "balding" Dsg3(bal)/Dsg3(bal) mice that carry a spontaneous null mutation in Dsg3. These PV IgGs caused gross skin blisters with PV-like suprabasal acantholysis and stained perilesional epidermis in a fishnet-like pattern, indicating that the PV phenotype can be induced without anti-Dsg 3 antibody. The anti-Dsg 1 antibody also was not required, as its presence in PV IgG does not alter the PV-like phenotype in skin organ cultures and because pemphigus foliaceus IgGs produce a distinct phenotype in Dsg3(null) mice. Therefore, mucocutaneous lesions in PV patients could be caused by non-Dsg antibodies.
Nguyen
V T
VT
Department of Dermatology, University of California at Davis, School of Medicine, Davis, California, USA.
Ndoye
A
A
Shultz
L D
LD
Pittelkow
M R
MR
Grando
S A
SA
D000051:Acantholysis / Q000276:immunology; D000818:Animals; D000831:Animals, Newborn; D001323:Autoantibodies / Q000097:blood / Q000276:immunology*; D016367:Baculoviridae / Q000235:genetics; D001768:Blister / Q000276:immunology / Q000473:pathology; D015820:Cadherins / Q000235:genetics* / Q000276:immunology*; D051183:Desmoglein 1; D051184:Desmoglein 3; D017353:Gene Deletion; D006651:Histocytochemistry; D006801:Humans; D007116:Immunization, Passive; D007074:Immunoglobulin G / Q000097:blood / Q000276:immunology; D015603:Keratinocytes / Q000276:immunology*; D051379:Mice; D018345:Mice, Knockout; D010392:Pemphigus / Q000097:blood / Q000235:genetics / Q000276:immunology* / Q000473:pathology*; D010641:Phenotype; D011993:Recombinant Fusion Proteins / Q000276:immunology; D012867:Skin / Q000276:immunology / Q000473:pathology
D001323:Autoantibodies; D015820:Cadherins; C071894:DSG3 protein, human; D051183:Desmoglein 1; D051184:Desmoglein 3; D007074:Immunoglobulin G; D011993:Recombinant Fusion Proteins