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Logo of arthrestherBioMed Centralbiomed central web sitesearchsubmit a manuscriptregisterthis articleArthritis Research & Therapy
 
Arthritis Res Ther. 2006; 8(4): R134.
Published online Jul 27, 2006. doi:  10.1186/ar2023
PMCID: PMC1779388
Mice expressing HLA-DQ6α8β transgenes develop polychondritis spontaneously
Jennifer L Lamoureux,1 Jane Hoyt Buckner,2 Chella S David,3 and David S Bradleycorresponding author1
1Department of Microbiology and Immunology, University of North Dakota School of Medicine and Health Sciences, Grand Forks, North Dakota, USA
2Benaroya Research Institute, Virginia Mason Medical Center, Seattle, Washington, USA
3Department of Immunology, Mayo Clinic College of Medicine, Rochester, Minnesota, USA
corresponding authorCorresponding author.
Jennifer L Lamoureux: jlamoure/at/medicine.nodak.edu; Jane Hoyt Buckner: jbuckner/at/vmresearch.org; Chella S David: chella.david/at/mayo.edu; David S Bradley: dbradley/at/medicine.nodak.edu
Received April 2, 2006; Revisions requested May 10, 2006; Revised July 20, 2006; Accepted July 27, 2006.
Abstract
Relapsing polychondritis (RP) is a human autoimmune disease of unknown etiology in which cartilaginous sites are destroyed by cyclic inflammatory episodes beginning, most commonly, during the fourth or fifth decade of life. We have previously described collagen-induced polychondritis that closely mirrors RP occurring in young (6–8 weeks old) HLA-DQ6αβ8αβ transgenic Aβ0 mice, following immunization with heterologous type II collagen (CII).
We present evidence here that transgenic strains expressing the DQ6α8β transgene develop spontaneous polychondritis (SP) at the mouse equivalent of human middle age (4.5–6 months and 40–50 years old, respectively) and display polyarthritis, auricular chondritis and nasal chondritis – three of the most common sites affected in RP. Auricular chondritis in SP, like RP but unlike CII-induced polychondritis, exhibited a relapsing/remitting phenotype, requiring several inflammatory cycles before the cartilage is destroyed. Elevated serum levels of total IgG corresponded with the onset of disease in SP, as in RP and CII-induced polychondritis. No CII-specific immune response was detected in SP, however – more closely mirroring RP, in which as few as 30% of RP patients have been reported to have CII-specific IgG. CII-induced polychondritis displays a strong CII-specific immune response. SP also demonstrated a strong female preponderance, as some workers have reported in RP but has not observed in CII-induced polychondritis. These characteristics of SP allow for the examination of the immunopathogenesis of polychondritis in the absence of an overwhelming CII-specific immune response and the strong adjuvant-induced immunostimulatory influence in CII-induced polychondritis.
This spontaneous model of polychondritis provides a new and unique tool to investigate both the initiatory events as well as the immunopathogenic mechanisms occurring at cartilaginous sites during the cyclic inflammatory assaults of polychondritis.
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