Animal Models of Spondyloarthritis

Taurog, Joel D.

doi:10.1007/978-1-4419-0298-6_18

Cited by 20 publications

(13 citation statements)

References 67 publications

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“…The lack of a robust disease-associated B27 transgenic mouse model was noted 100 , and it was suggested by Dr. Sartor and others that effort be made to identify a combination of genetic background and gene knockouts that might allow penetrance of a SpA phenotype in mice. It was also noted that technology now exists, and systematic efforts are now being made, to produce gene knockouts in rats 101 .…”

Section: Hla-b27 Transgenic Ratsmentioning

confidence: 98%

The Role of HLA-B27 in Spondyloarthritis

Taurog¹

2010

J Rheumatol

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This article summarizes the proceedings of a one-day international workshop held in July 2009 on the role of HLA-B27 in the pathogenesis of ankylosing spondylitis (AS) and related disorders. HLA-B27 is found in about 90% of patients with AS, with an odds ratio of about 100, but the mechanism underlying this association is not known. There are currently 3 major mechanistic hypotheses for this association: (1) T cell recognition of one or more B27 presented peptides; (2) B27 heavy-chain misfolding that induces an unfolded protein response; and (3) innate immune recognition of cell-surface expressed B27 heavy-chain dimers. None of these hypotheses accounts for the tissue specificity of the inflammation characteristic of AS. These hypotheses were discussed in the context of known epidemiologic, biochemical, structural, and immunologic differences among HLA-B27 subtypes; data from the HLA-B27 transgenic rat model of spondyloarthritis; the growing list of other genes that have been found to be associated with AS; and other data on the pathogenesis of spondyloarthritis. Proposed directions for future research include expanded efforts to define similarities and differences among the B27 subtypes; further development of animal models; identifying the interactions of B27 with the products of other genes associated with AS; and continued investigation into the pathogenesis of spondyloarthritis.

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Section: Hla-b27 Transgenic Ratsmentioning

confidence: 98%

The Role of HLA-B27 in Spondyloarthritis

Taurog¹

2010

J Rheumatol

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“…For this reason, SpA appears as one of the best examples of the diseases related to the HLA marker. Human and transgenic animal model link and relation studies have proven the role of B27 in AS (Taurog, 2009;Thomas and Brown, 2010).…”

Section: Introductionmentioning

confidence: 99%

Distribution of HLA-B27 and CYP2D6*4 mutations in the middle Black Sea area (Tokat) of Turkey

Şahín¹,

Aydoğan²,

Benli³

et al. 2011

Genet. Mol. Res.

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ABSTRACT. We analyzed distribution of HLA-B27 and CYP2D6*4 mutations in 249 patients from Tokat province in Turkey with symptoms of arthritis, sacroiliac, joint and back pain, using a LightCycler 480 II Real-Time PCR thermal cycler. The Genes-4U was applied for studying HLA-B27 mutation, and the Tib-Molbiol commercial kit was used to examine the CYP2D6*4 mutation. Among the 249 patients, 18.5% had the HLA-B27 mutation. The CYP2D6*4 mutation was found in 22.0% (six homozygotes). Ten patients had both mutations. These frequencies are similar to what has been reported from other populations.

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“…Noteworthy, some of these alleles such as the B*2709 in Sardinia (12,13) and the B*2706 in Asia (14), are not associated with AS since they have not been reported, except anecdotically, in patients, and therefore have become a powerful tool to gain insights into disease association. Functional differences between AS-associated and non-AS-associated B27 subtypes (15), B27 transgenic animal models (16) and a recent report showing an association between AS and ERAP1 (17), an ER aminopeptidase trimming the peptides presented by the HLA-class I molecules, strongly suggest a direct role for the HLA-B27 molecules in disease pathogenesis, possibly presenting tissue-specific peptides (18).…”

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confidence: 99%

Characterization of a Proteasome and TAP-independent Presentation of Intracellular Epitopes by HLA-B27 Molecules

Magnacca

Persiconi

Nurzia

et al. 2012

Journal of Biological Chemistry

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Nascent HLA-class I molecules are stabilized by proteasome-derived peptides in the ER and the new complexes proceed to the cell surface through the post-ER vesicles. It has been shown, however, that less stable complexes can exchange peptides in the Trans Golgi Network (TGN). HLA-B27 are the most studied HLA-class I molecules due to their association with Ankylosing Spondylitis (AS). Chimeric proteins driven by TAT of HIV have been exploited by us to deliver viral epitopes, whose cross-presentation by the HLA-B27 molecules was proteasome and TAP-independent and not restricted to Antigen-Presenting Cells (APC). Here, using these chimeric proteins as epitope suppliers, we compared with each other and with the HLA-A2 molecules, the two HLA-B*2705 and B*2709 alleles differing at residue 116 (D116H) and differentially associated with AS. We found that the antigen presentation by the two HLA-B27 molecules was proteasome-, TAP-, and APC-independent whereas the presentation by the HLA-A2 molecules required proteasome, TAP and professional APC. Assuming that such difference could be due to the unpaired, highly reactive Cys-67 distinguishing the HLA-B27 molecules, C67S mutants in HLA-B*2705 and B*2709 and V67C mutant in HLA-A*0201 were also analyzed. The results showed that this mutation did not influence the HLA-A2-restricted antigen presentation while it drastically affected the HLA-B27-restricted presentation with, however, remarkable differences between B*2705 and B*2709. The data, together with the occurrence on the cell surface of unfolded molecules in the case of C67S-B*2705 mutant but not in that of C67SB*2709 mutant, indicates that Cys-67 has a more critical role in stabilizing the B*2705 rather than the B*2709 complexes

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Animal Models of Spondyloarthritis

Cited by 20 publications

References 67 publications

The Role of HLA-B27 in Spondyloarthritis

The Role of HLA-B27 in Spondyloarthritis

Distribution of HLA-B27 and CYP2D6*4 mutations in the middle Black Sea area (Tokat) of Turkey

Characterization of a Proteasome and TAP-independent Presentation of Intracellular Epitopes by HLA-B27 Molecules

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