The humanized SCID mouse model to study HLA class II-linked autoimmunity to desmoglein 3 in pemphigus vulgaris.

Abstract

BACKGROUND:

Pemphigus vulgaris (PV) is a severe autoimmmune skin disorder induced by antibodies against desmoglein (Dsg) 3 on epidermal keratinocytes.

OBJECTIVES:

To establish an active animal model of PV to analyse the T-cell-regulated production of pathogenic antibodies in vivo.

METHODS:

Immunodeficient SCID mice were injected with peripheral blood lymphocytes (PBL) from an HLA-DRB1*0402/DQ8+ patient with PV or a DRB1*0402/DQ8+ healthy donor, with or without subsequent injections of human Dsg3 or preincubation of PBL with Dsg3.

RESULTS:

Human immunoglobulins (2.7-18.5 mg mL-1) were detected in all the mice after 8 weeks. Only one of 30 PBL-treated mice developed IgM against Dsg3 and showed intercellular IgM deposits in skin, nostrils and tongue. In contrast, in a previous study, 41% of SCID mice injected with PBL from patients with PV developed anti-Dsg3 antibodies in vivo.

CONCLUSIONS:

Our inability to reproduce these findings may be due to the transfer of slightly lower numbers of PBL (20 x 10(6) vs. 25-30 x 10(6)).

• Authors: T Rädisch, R Riechers, M Hertl
• Journal: The British journal of dermatology (Br J Dermatol) Vol. 146 Issue 2 Pg. 189-93 (Feb 2002) ISSN: 0007-0963 [Print] England
• PMID: 11903226 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Cadherins
• DSG3 protein, human
• Desmoglein 3
• HLA-DR Antigens
• HLA-DRB1 Chains
• HLA-DRB1*04:02 antigen
• Immunoglobulin M

Topics

• Animals
• Autoimmunity
• Cadherins (immunology)
• Desmoglein 3
• Disease Models, Animal
• Female
• HLA-DR Antigens (immunology)
• HLA-DRB1 Chains
• Humans
• Immunoglobulin M (biosynthesis)
• Lymphocyte Transfusion
• Mice
• Mice, SCID
• Models, Animal
• Pemphigus (immunology)