HLA-B27 and Human β2-Microglobulin Affect the Gut Microbiota of Transgenic Rats
Phoebe Lin,Mary Bach,Mark Asquith,Aaron Y. Lee,Lakshmi Akileswaran,Patrick Stauffer,Sean Davin,Yuzhen Pan,Eric D. Cambronne,Martha L. Dorris,Justine W. Debelius,Christian L. Lauber,Gail Ackermann,Yoshiki Vazquez Baeza,Tejpal Gill,Rob Knight,Robert A. Colbert,Joel D. Taurog,Russell N. Van Gelder,James T. Rosenbaum +19 more
TL;DR: The finding that HLA-B27 is associated with altered cecal microbiota has not been shown before and can potentially provide a better understanding of the clinical diseases associated with this gene.
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Abstract: The HLA-B27 gene is a major risk factor for clinical diseases including ankylosing spondylitis, acute anterior uveitis, reactive arthritis, and psoriatic arthritis, but its mechanism of risk enhancement is not completely understood. The gut microbiome has recently been shown to influence several HLA-linked diseases. However, the role of HLA-B27 in shaping the gut microbiome has not been previously investigated. In this study, we characterize the differences in the gut microbiota mediated by the presence of the HLA-B27 gene. We identified differences in the cecal microbiota of Lewis rats transgenic for HLA-B27 and human β2-microglobulin (hβ2m), compared with wild-type Lewis rats, using biome representational in situ karyotyping (BRISK) and 16S rRNA gene sequencing. 16S sequencing revealed significant differences between transgenic animals and wild type animals by principal coordinates analysis. Further analysis of the data set revealed an increase in Prevotella spp. and a decrease in Rikenellaceae relative abundance in the transgenic animals compared to the wild type animals. By BRISK analysis, species-specific differences included an increase in Bacteroides vulgatus abundance in HLA-B27/hβ2m and hβ2m compared to wild type rats. The finding that HLA-B27 is associated with altered cecal microbiota has not been shown before and can potentially provide a better understanding of the clinical diseases associated with this gene.
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Citations
Ankylosing Spondylitis and Axial Spondyloarthritis
TL;DR: The clinical definition of ankylosing spONDylitis and axial spondyloarthritis is summarized, the pathogenesis of these conditions is discussed, and approaches to management are reviewed.
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The role of the gut microbiome in systemic inflammatory disease
TL;DR: This review summarizes the preclinical and clinical evidence on how dietary, probiotic, prebiotic, and microbiome based therapeutics affect the understanding of wellness and disease, particularly in autoimmunity.
502
The Gut Microbiota in Immune-Mediated Inflammatory Diseases.
Jessica D. Forbes,Jessica D. Forbes,Gary Van Domselaar,Gary Van Domselaar,Charles N. Bernstein +4 more
TL;DR: The main challenge now is to determine if alterations of gut flora are common between IMID or, if particular changes in the gut community are in fact specific to a single disease.
Brief Report: Intestinal Dysbiosis in Ankylosing Spondylitis
Mary-Ellen Costello,Francesco Ciccia,Dana Willner,Nicole M. Warrington,Philip Robinson,Brooke Gardiner,Mhairi Marshall,Tony J. Kenna,Giovanni Triolo,Matthew A. Brown +9 more
TL;DR: In this article, the authors show evidence for a discrete microbial signature in the terminal ileum of patients with ankylosing spondylitis compared with healthy control subjects.
Quantitative metagenomics reveals unique gut microbiome biomarkers in ankylosing spondylitis
Chengping Wen,Zhijun Zheng,Tiejuan Shao,Lin Liu,Zhijun Xie,Zhixing He,Wendi Zhong,Yongsheng Fan,Linshuang Zhang,Haichang Li,Chunyan Wu,Changfeng Hu,Qian Xu,Jia Zhou,Shunfeng Cai,Dawei Wang,Yun Huang,Maxime Breban,Nan Qin,Stanislav D Ehrlich,Stanislav D Ehrlich +20 more
TL;DR: The data suggest biomarkers identified in this study might participate in the pathogenesis or development process of ankylosing spondylitis, providing new leads for the development of new diagnostic tools and potential treatments.
References
CD8αβ T Cells Are Not Essential to the Pathogenesis of Arthritis or Colitis in HLA-B27 Transgenic Rats
Ekkehard May,Martha L. Dorris,Nimman Satumtira,Imran Iqbal,Muhammad I. Rehman,Ellis Lightfoot,Joel D. Taurog +6 more
TL;DR: The data indicate that HLA-B27-retricted CD8+ T cells are unlikely to serve as effector cells in the transgenic rat model of HLA, B27-associated disease, in opposition to a commonly invoked hypothesis concerning the role of B27 in the spondyloarthropathies.
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Additional human β2-microglobulin curbs HLA–B27 misfolding and promotes arthritis and spondylitis without colitis in male HLA–B27–transgenic rats
Tri M. Tran,Martha L. Dorris,Nimman Satumtira,James A. Richardson,Robert E. Hammer,Jie Shang,Joel D. Taurog +6 more
TL;DR: The results suggest that B27 misfolding is associated with intestinal inflammation, but that neither B27Misfolding nor intestinal inflammation is critical to the development of B27-associated arthropathy.
164
Spondylarthritis in HLA–B27/human β2‐microglobulin–transgenic rats is not prevented by lack of CD8
Joel D. Taurog,Martha L. Dorris,Nimman Satumtira,Tri M. Tran,Rohit Sharma,Ralf Dressel,Jens van den Brandt,Holger M. Reichardt +7 more
TL;DR: All of the previously described disease manifestations in HLA-B27/Hubeta(2)m-transgenic rats arise in the absence of any functional CD8+ T cells, so it seems unlikely that classic T cell recognition of HLA -B27 is of primary importance in this animal model.
148
HLA‐B27 modulates intracellular survival of Salmonella enteritidis in human monocytic cells
TL;DR: It is demonstrated that the expression of the HLA‐B27 antigen does not influence the uptake of S. enteritidis into U937 cells in vitro, and Interestingly, HLA•B27 remarkably impairs the elimination of S.'s enter itidis within the Hla‐B 27 transfected U9 37 cells.
116
A hypothesis for the HLA-B27 immune dysregulation in spondyloarthropathy: contributions from enteric organisms, B27 structure, peptides bound by B27, and convergent evolution
TL;DR: It is concluded that HLA-B27 and enteric Gram-negative bacteria have undergone a previously unappreciated form of convergent evolution which may be important in the process leading to these rheumatic diseases.
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