The microbiome and HLA-B27-associated acute anterior uveitis

Rosenbaum, James T.; Asquith, Mark

doi:10.1038/s41584-018-0097-2

Cited by 128 publications

(116 citation statements)

References 114 publications

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“…Strong cofamiliality (14) and the extensive sharing of genetic factors between AS and inflammatory bowel disease (IBD) (15,16) suggests a shared etiopathogenesis. This is consistent with the hypothesis that gut-derived immune cells or microbial products may contribute to spondyloarthritic inflammation (17)(18)(19).…”

Section: Introductionsupporting

confidence: 91%

HLA alleles associated with risk of ankylosing spondylitis and rheumatoid arthritis influence the gut microbiome

Asquith

Sternes

Costello

et al. 2019

Preprint

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Objective. HLA alleles affect susceptibility to more than 100 diseases, but the mechanisms that account for these genotype-disease associations are largely unknown. HLA alleles strongly influence predisposition to ankylosing spondylitis (AS) and rheumatoid arthritis (RA). Both AS and RA patients have discrete intestinal and fecal microbiome signatures. Whether these changes are the cause or consequence of the diseases themselves is unclear. To distinguish these possibilities, we examined the effect of HLA-B27 and HLA-DRB1 RA risk alleles on the composition of the intestinal microbiome in healthy individuals.Methods. Five hundred sixty-eight stool and biopsy samples from 6 intestinal sites were collected from 107 healthy unrelated subjects, and stool samples were collected from 696 twin pairs from the TwinsUK cohort. Microbiome profiling was performed using sequencing of the 16S ribosomal RNA bacterial marker gene. All subjects were genotyped using the Illumina CoreExome SNP microarray, and HLA genotypes were imputed from these data.Results. Associations were observed between the overall microbial composition and both the HLA-B27 genotype and the HLA-DRB1 RA risk allele (P = 0.0002 and P = 0.00001, respectively). These associations were replicated using the stool samples from the TwinsUK cohort (P = 0.023 and P = 0.033, respectively).Conclusion. This study shows that the changes in intestinal microbiome composition seen in AS and RA are at least partially due to effects of HLA-B27 and HLA-DRB1 on the gut microbiome. These findings support the hypothesis that HLA alleles operate to cause or increase the risk of these diseases through interaction with the intestinal microbiome and suggest that therapies targeting the microbiome may be effective in preventing or treating these diseases.

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Section: Introductionsupporting

confidence: 91%

HLA alleles associated with risk of ankylosing spondylitis and rheumatoid arthritis influence the gut microbiome

Asquith

Sternes

Costello

et al. 2019

Preprint

Self Cite

View full text Add to dashboard Cite

show abstract

“…Strong cofamiliality and the extensive sharing of genetic factors between AS and inflammatory bowel disease (IBD) suggests a shared etiopathogenesis. This is consistent with the hypothesis that gut‐derived immune cells or microbial products may contribute to spondyloarthritic inflammation .…”

Section: Introductionsupporting

confidence: 91%

HLA Alleles Associated With Risk of Ankylosing Spondylitis and Rheumatoid Arthritis Influence the Gut Microbiome

Asquith¹,

Sternes

Costello

et al. 2019

Arthritis & Rheumatology

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135

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Objective HLA alleles affect susceptibility to more than 100 diseases, but the mechanisms that account for these genotype–disease associations are largely unknown. HLA alleles strongly influence predisposition to ankylosing spondylitis (AS) and rheumatoid arthritis (RA). Both AS and RA patients have discrete intestinal and fecal microbiome signatures. Whether these changes are the cause or consequence of the diseases themselves is unclear. To distinguish these possibilities, we examined the effect of HLA–B27 and HLA–DRB1 RA risk alleles on the composition of the intestinal microbiome in healthy individuals. Methods Five hundred sixty‐eight stool and biopsy samples from 6 intestinal sites were collected from 107 healthy unrelated subjects, and stool samples were collected from 696 twin pairs from the TwinsUK cohort. Microbiome profiling was performed using sequencing of the 16S ribosomal RNA bacterial marker gene. All subjects were genotyped using the Illumina CoreExome SNP microarray, and HLA genotypes were imputed from these data. Results Associations were observed between the overall microbial composition and both the HLA–B27 genotype and the HLA–DRB1 RA risk allele (P = 0.0002 and P = 0.00001, respectively). These associations were replicated using the stool samples from the TwinsUK cohort (P = 0.023 and P = 0.033, respectively). Conclusion This study shows that the changes in intestinal microbiome composition seen in AS and RA are at least partially due to effects of HLA‐B27 and HLA–DRB1 on the gut microbiome. These findings support the hypothesis that HLA alleles operate to cause or increase the risk of these diseases through interaction with the intestinal microbiome and suggest that therapies targeting the microbiome may be effective in preventing or treating these diseases.

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“…This observation led us to hypothesize that there is an opposing interaction between uveitis and radiographic progression. The uvea is the vascular middle layer of the eye, composed of the iris, ciliary body, and choroid [37]. The ciliary body includes the ciliary muscle and is connected to the lens through the zonular fiber, which is the suspensory ligament of the lens [38].…”

Section: Discussionmentioning

confidence: 99%

Association of Uveitis with Radiographic Progression in Patients with Axial Spondyloarthritis: A Propensity Score Matching Analysis

2019

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Objective. Acute anterior uveitis (AAU) is the most common extra-articular manifestation in patients with axial spondyloarthritis (axSpA). However, the relationship between AAU and radiographic progression in axSpA remains unclear. Hence, we investigated whether the presence of AAU is associated with radiographic structural damage in patients with axSpA. Methods. Clinical and radiographic data were obtained from 253 patients with axSpA. Radiographic progression over 2 years was assessed using the modified Stoke Ankylosing Spondylitis Spine Score (mSASSS). Progression was defined as mSASSS worsening by ≥two units. Using propensity score (PS) matching, differences between patients with and without AAU were analyzed. Results. The proportion of progressors among patients with AAU was lower than that of patients without AAU (13.6% vs. 29.5%, p=0.058). The rate of increase in mSASSS and number of syndesmophytes were lower in patients with AAU than patients without AAU (0.57±1.37 vs. 1.02±1.79, p=0.085 and 0.46±1.45 vs. 0.83±1.62, p=0.158). In multivariate regression analysis, presence of AAU was independently associated with slowed radiographic progression (odds ratio [95% confidence interval] 0.21 [0.07, 0.67], p=0.004). Conclusion. PS-matched axSpA patients with AAU showed significantly less radiographic progression than those without AAU. (J Rheum Dis 2019;26:248-256)

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The microbiome and HLA-B27-associated acute anterior uveitis

Cited by 128 publications

References 114 publications

HLA alleles associated with risk of ankylosing spondylitis and rheumatoid arthritis influence the gut microbiome

HLA alleles associated with risk of ankylosing spondylitis and rheumatoid arthritis influence the gut microbiome

HLA Alleles Associated With Risk of Ankylosing Spondylitis and Rheumatoid Arthritis Influence the Gut Microbiome

Association of Uveitis with Radiographic Progression in Patients with Axial Spondyloarthritis: A Propensity Score Matching Analysis

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