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Br J Dermatol. 2011 Sep;165(3):552-62. doi: 10.1111/j.1365-2133.2011.10463.x.

IgG-induced clustering of desmogleins 1 and 3 in skin of patients with pemphigus fits with the desmoglein nonassembly depletion hypothesis.

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1
Department of Dermatology, Centre for Blistering Diseases, University Medical Centre Groningen, University of Groningen, Hanzeplein 1, 9713 GZ Groningen, The Netherlands.

Abstract

BACKGROUND:

In pemphigus circulating IgG is present with the desmosomal cadherins desmoglein (Dsg) 1 and 3. In the epidermis of patients, this IgG deposits in a pattern that is often partly granular and does not reflect the normal Dsg distribution.

OBJECTIVE:

To understand why the IgG deposits in a granular pattern in the skin of patients with pemphigus.

PATIENTS/METHODS:

We analysed the distribution of IgG and desmosomal adhesion molecules in skin biopsies of 18 patients with pemphigus vulgaris (PV) and 10 with pemphigus foliaceus (PF) by double staining immunofluorescence. The effect of IgG on desmosomal proteins was studied in an in vitro skin model.

RESULTS:

In PF skin Dsg1, but not Dsg3, was aberrantly distributed in the same partly granular pattern as the IgG. Vice versa, in skin of PV patients with anti-Dsg3 antibodies, Dsg3, but not Dsg1, colocalized with the granular IgG. Plakoglobin also coclustered with IgG and Dsg, but this was far more prominent with Dsg1 than with Dsg3. In areas of heavy Dsg1 clustering, but not in areas of heavy Dsg3 clustering, intercellular widening between keratinocytes was present. Patient IgG, but not Fab fragments, induced the same Dsg clustering in vitro.

CONCLUSIONS:

The IgG-induced clustering of the Dsg autoantigens underlies the granular IgG deposition in patient skin. In PF and in mucocutaneous PV, Dsg1 clustering, but not Dsg3 clustering, correlates with nonacantholytic intercellular widening between desmosomes. In the patient the Dsg becomes sequestered from desmosomal components which fits in with the desmoglein nonassembly depletion hypothesis, indicating that targeted nonjunctional Dsg is no longer available to be incorporated into desmosomes and this leads to disturbed assembly, and Dsg-depleted desmosomes.

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