HLA–B27 Subtype Oligomerization and Intracellular Accumulation Patterns Correlate With Predisposition to Spondyloarthritis

@article{Jeanty2014HLAB27SO,
  title={HLA–B27 Subtype Oligomerization and Intracellular Accumulation Patterns Correlate With Predisposition to Spondyloarthritis},
  author={C Jeanty and Ad{\`e}le Sourisce and Aur{\'e}lie Noteuil and Nad{\`e}ge Jah and Aurore Wielgosik and Ingrid Fert and Maxime Breban and Claudine Andr{\'e}},
  journal={Arthritis \& Rheumatology},
  year={2014},
  volume={66}
}
Mechanisms underlying the striking association of spondyloarthritis (SpA) with the class I major histocompatibility complex molecule HLA–B27 remain poorly understood. SpA‐like disease develops spontaneously in B*2705‐transgenic rats, in conjunction with high HLA–B27 expression levels. This study was undertaken to examine the effects of increased expression of HLA–B27 alleles that are differentially associated with SpA on oligomerization and intracellular redistribution. 

HLA–B27 Subtypes Predisposing to Ankylosing Spondylitis Accumulate in an Endoplasmic Reticulum–Derived Compartment Apart From the Peptide‐Loading Complex

This study was undertaken to characterize the nature and content of HLA–B–containing vesicles and to further examine their relevance to SpA predisposition.

Differences in Cellular Clearing Mechanisms of Aggregates of Two Subtypes of HLA-B27

A clear difference was observed in protein clearance mechanisms: whereas unfolded protein response, autophagy, and aggresomes were involved in the degradation of B*2704, the endosome–lysosome machinery was primarily involved in B* 2709 degradation.

Revisiting MHC Genes in Spondyloarthritis

Candidate-gene approaches and genome-wide studies have recently allowed identification of several new loci residing outside of the MHC region that are involved in the predisposition to SpA, and some of those new genes code for aminopeptidases that were involved in MHC class I presentation and were shown to interact with HLA-B27.

Ankylosing Spondylitis: A Multi-Factorial Autoimmune Disease. MHC Class I, Antigen Presentation and others to Blame

This review highlights the different HLA -B27 hypotheses, as well as the roles of some of the other factors in determining AS susceptibility, and concludes that, individually, none of these factors can take complete credit for causing AS since it is a multi-factorial autoimmune disease.

Editorial: HLA–B27: The Story Continues to Unfold

Aberrant folding and unfolding of HLA–B27 have been linked to the IL-23–IL-17 axis through UPR-mediated increases in IL- 23 production, and triggering of CD41 Th17 T cells that express KIR3DL2, respectively.

Polymorphisms in the F Pocket of HLA–B27 Subtypes Strongly Affect Assembly, Chaperone Interactions, and Heavy‐Chain Misfolding

The purpose of this study was to investigate the factors that influence differences in dimerization between disease‐associated and non–disease‐associated HLA–B27 alleles.

The enigmatic role of HLA-B*27 in spondyloarthritis pathogenesis

High-throughput TCR (T cell receptor) sequencing has provided evidence for reduced clonal expansion and increased TCR diversity in ankylosing spondylitis and two common CD8+ TCR sequences identified in one study, similar CD8 and CD4 TCR motifs were found in another study.

The role of the unfolded protein response in axial spondyloarthritis

A major outcome of ER stress, the unfolded protein response (UPR), as well as consequences of the UPR for inflammation and autophagy are described, particularly intriguing given the centrality of cytokines in spondyloarthritis.

HLA-B27 alters BMP/TGFβ signalling in Drosophila, revealing putative pathogenic mechanism for spondyloarthritis

Antagonistic interaction of HLA-B27 with ALK2, which exerts inhibitory functions on the TGFβ/BMP signalling pathway at the cross-road between inflammation and ossification, could adequately explain SpA development.

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