Faculty Collaboration Database

Sequential intramolecular epitope spreading of humoral responses to human BPAG2 in a transgenic model. J Invest Dermatol 2010 Apr;130(4):1040-7

Date

10/09/2009

Pubmed ID

19812601

DOI

10.1038/jid.2009.309

Scopus ID

2-s2.0-77949538894 (requires institutional sign-in at Scopus site)   25 Citations

Abstract

Bullous pemphigoid (BP) is a subepidermal autoimmune disease characterized by a humoral response to an epidermal basement membrane (BM) component, BP antigen 2 (BPAG2). BP patients have IgG autoantibodies against an immunodominant BPAG2 extracellular domain termed NC16A as well as additional epitopes located both in the intracellular and extracellular domains (ICD and ECD, respectively) of this autoantigen. To study the evolution of humoral responses to BPAG2, sequential serum samples obtained from C57BL/6Ncr mice grafted with otherwise syngeneic skin from transgenic mice expressing human BPAG2 (hBPAG2) in epidermal BM were studied for IgG reactivity to seven ECD and ICD hBPAG2 epitopes. All grafted mice developed specific IgG against hBPAG2 ECD and ICD epitopes. In seven of eight mice, anti-hBPAG2 IgG was initially directed against ECD epitopes; in six mice, humoral responses subsequently targeted additional ECD and ICD BPAG2 epitopes. In contrast to IgG specific for ECD epitopes, IgG against ICD epitopes was present at lower levels, detectable for shorter periods, and non-complement fixing. Interestingly, the appearance of IgG directed against ICD epitopes correlated with the development of graft loss in this experimental model. These studies provide a comprehensive and prospective characterization of the evolution of humoral immune responses to hBPAG2 in vivo.

Author List

Di Zenzo G, Calabresi V, Olasz EB, Zambruno G, Yancey KB

Author

Edit Olasz MD, PhD Associate Professor in the Dermatology department at Medical College of Wisconsin

MESH terms used to index this publication - Major topics in bold

Animals
Autoantigens
Cytoplasm
Epidermis
Epitopes
Extracellular Space
Female
Humans
Immunity, Humoral
Immunoglobulin G
Male
Mice
Mice, Inbred C57BL
Mice, Transgenic
Non-Fibrillar Collagens
Pemphigoid, Bullous
Protein Structure, Tertiary
Skin Transplantation