The role of MHC class I heterodimer expression in mouse ankylosing enthesopathy

Abstract

The role of MHC class I heterodimer expression in mouse ankylosing enthesopathy Weinreich, S.S.; Hoebe-Hewryk, B.; van der Horst, A.R.; Boog, C.J.P.; Ivanyi, P.

Development of spontaneous arthritis in β2-microglobulin-deficient mice without expression of HLA-B27: Association with deficiency of endogenous major histocompatibility complex class I expression

“…Although the ankle lesions of SA bear some resemblance to ANKENT, particularly in later stages when ankylosis may occur, ANKENT has not been reported to involve IP and MTP joints, does not require ␤ 2 m deficiency or an environmental trigger, and is very uncommon in mice younger than 4 months (3,4). SA appears clinically similar to a spontaneous arthropathy described in DBA/1 mice (16).…”

“…In contrast, SA has been reported in only B27-tg mice that are genetically deficient in endogenous ␤ 2 m (␤ 2 m 0 ), and its development requires that animals be exposed to a non-SPF environment (5). Surprisingly, although a ␤ 2 m 0 background is required for SA, it actually reduces the incidence of ANKENT (3). Differences in age at onset, phenotypic and pathologic characteristics, dependence on mouse ␤ 2 m, and the need for an environmental trigger suggest that ANKENT and SA are distinct processes.…”

“…Transgenic (tg) rodent models with HLA-B27-associated arthropathy have provided strong evidence that this major histocompatibility complex (MHC) class I protein can have a direct role in the pathogenesis of arthritis (1)(2)(3). However, phenotypic differences between the models and variations in the requirements for expression of B27 and ␤ 2 -microglobulin (␤ 2 m) are not yet fully understood.…”

Cytokines and the immunopathology of the spondyloarthropathies

“…The same author has now published the histologic work [122] on ankylosing enthesopathy mice (ANKENT) that have been extensively studied by Weinreich and Ivanyi [123]. This model, which seems to be relatively independent of HLA B27, might be useful to further study the link between inflammation, new bone formation and ankylosis.…”

Pathogenicity of Misfolded and Dimeric HLA-B27 Molecules

“…ANKENT, a spontaneous and progressive ankylosing enthesopathy affecting ankle/tarsal joints of ageing mice, demonstrates both MHC and non-MHC linked predisposition, male predominance, and histological enthesitis. The mouse H-2 k haplotype appears to be an important risk factor, and the introduction of HLA-B*2702 increased the incidence of joint tarsal ankylosis [47–49]. Also, disrupting the MHC class I pathway either by knocking out the light chain β 2m or TAP (which actively transports peptides into the ER lumen for MHC class I presentation) can lead to the spontaneous development of a mild arthritis on some mouse genetic backgrounds.…”