Mice expressing HLA-DQ6α8β transgenes develop polychondritis spontaneouslyReportar como inadecuado




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Arthritis Research and Therapy

, 8:R134

First Online: 27 July 2006Received: 02 April 2006Revised: 20 July 2006Accepted: 27 July 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.

AbbreviationsBSAbovine serum albumin

CIItype II collagen

ELISAenzyme-linked immunosorbent assay

G6PIglucose-6-phosphate-isomerase

PBSphosphate-buffered saline

RPrelapsing polychondritis

SPspontaneous polychondritis

tgtransgenic

TGF-βtransforming growth factor beta.

Electronic supplementary materialThe online version of this article doi:10.1186-ar2023 contains supplementary material, which is available to authorized users.

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Autor: Jennifer L Lamoureux - Jane Hoyt Buckner - Chella S David - David S Bradley

Fuente: https://link.springer.com/







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