The Association Between <scp>HLA</scp> Genetic Susceptibility Markers and Sonographic Enthesitis in Psoriatic Arthritis

Polachek, Ari; Cook, Richard J.; Chandran, Vinod; Abji, Fatima; Gladman, Dafna D.; Eder, Lihi

doi:10.1002/art.40423

Cited by 15 publications

(8 citation statements)

References 34 publications

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“…Although these early studies established the link between HLA-B27 and the development of AS, a 2015 study found no association between HLA-B27 and the rate of spinal radiographic progression 58 . HLA-B27 is also predictive of peripheral enthesitis in patients with PsA 59 , but HLA-B27 contributes less to the risk of peripheral arthritis than axial arthritis 60,61 and is not a risk factor for IBD 18 . To date, no conclusive role for CD8 + T cells has been recognized in SpA, despite the strong association with MHC class I alleles; thus, a number of alterative hypotheses have been proposed to explain the role of HLA-B27 in the pathogenesis of SpA, which have been reviewed extensively elsewhere 62,63 .…”

Section: Spa Is a Genetically Driven Diseasementioning

confidence: 99%

Revisiting the gut–joint axis: links between gut inflammation and spondyloarthritis

et al. 2020

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Gut inflammation is strongly associated with spondyloarthritis (SpA), as exemplified by the high prevalence of inflammatory bowel disease (IBD) and the even higher occurrence of subclinical gut inflammation in patients with SpA. The gut-joint axis of inflammation in SpA is further reinforced by similarities in immunopathogenesis at both anatomical sites and by the clinical success of therapies blocking TNF and IL-23 in IBD and in some forms of SpA. Many genetic risk factors are shared between SpA and IBD, and changes in the composition of gut microbiota are seen in both diseases. Current dogma is that inflammation in SpA initiates in the gut and leads to joint inflammation; however, although conceptually attractive, some research does not support this causal relationship. For example, therapies targeting IL-17A are efficacious in the joint but not the gut, and interfering with gut trafficking by targeting molecules such as α4β7 in IBD can lead to onset or flares of SpA. Several important knowledge gaps remain that must be addressed in future studies. Determining the true nature of the gut-joint axis has real-world implications for the treatment of patients with co-incident IBD and SpA and for the repurposing of therapeutics from one disease to the other.

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Section: Spa Is a Genetically Driven Diseasementioning

confidence: 99%

Revisiting the gut–joint axis: links between gut inflammation and spondyloarthritis

et al. 2020

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“…Previous research into the pathogenic mechanisms underlying PsA clinical features identified few potential sources. Genetic studies have shown that HLA-B*27 was associated with sonographic enthesitis [ 28 ] and axial involvement [ 4 ] while HLA-B*08 was associated with synovial-based features including joint deformity and fusion [ 3 ]. Sokolova et al showed that the IL-17 induced proteins, beta-defensin-2 and lipocalin-2, were associated with a subset of patients with enthesitis while products of innate immune system activation and neutrophil activation were associated with a subset of patient with peripheral arthritis [ 6 ].…”

Section: Discussionmentioning

confidence: 99%

Defining imaging sub-phenotypes of psoriatic arthritis: integrative analysis of imaging data and gene expression in a PsA patient cohort

Eder

Rahmati

et al. 2022

Rheumatology

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Objectives To define imaging sub-phenotypes in patients with psoriatic arthritis (PsA); determine their association with whole blood gene expression, and identify biological pathways characterizing the sub-phenotypes. Methods 55 patients with PsA ready to initiate treatment for active disease were prospectively recruited. We performed musculoskeletal ultrasound assessment of the extent of inflammation in the following domains: synovitis, peritenonitis, tenosynovitis, and enthesitis. Peripheral whole blood was profiled with RNAseq, and gene expression data were obtained. First, unsupervised cluster analysis was performed to define imaging sub-phenotypes that reflected the predominant tissue involved. Subsequently, principal component analysis was used to determine the association between imaging-defined sub-phenotypes and peripheral blood gene expression profile. Pathway enrichment analysis was performed to identify underlying mechanisms that characterize individual sub-phenotypes. Results Cluster analysis revealed three imaging sub-phenotypes: 1) Synovitis predominant (N = 31 [56%]); 2) Enthesitis predominant (N = 13 [24%]); 3) Peritenonitis predominant (N = 11 [20%]). The peritenonitis-predominant sub-phenotype had the most severe clinical joint involvement whereas the enthesitis-predominant sub-phenotype had the highest tender entheseal count. Unsupervised clustering of gene expression data identified three sub-phenotypes that partially overlapped with the imaging sub-phenotypes suggesting biological and clinical relevance of these sub-phenotypes. We therefore characterized enriched differential pathways, which included: immune system (innate system, B cells and neutrophil degranulation), complement system, platelet activation and coagulation function. Conclusions We identified three sub-phenotypes based on the predominant tissue involved in patients with active PsA. Distinct biological pathways may underlie these imaging sub-phenotypes seen in PsA, suggesting their biological and clinical importance.

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“…In addition to mechanical stress, Polachek et al discovered an increased risk of enthesitis in PsA with HLA-B27-positive results among 225 patients ( 134 ). A similar effect of HLA-B27 occurs in juvenile idiopathic arthritis (JIA) ( 135 ).…”

Section: Hla-b27 Tuned Immunitymentioning

confidence: 99%

Joint together: The etiology and pathogenesis of ankylosing spondylitis

Xiong

Cai

et al. 2022

Front. Immunol.

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Spondyloarthritis (SpA) refers to a group of diseases with inflammation in joints and spines. In this family, ankylosing spondylitis (AS) is a rare but classic form that mainly involves the spine and sacroiliac joint, leading to the loss of flexibility and fusion of the spine. Compared to other diseases in SpA, AS has a very distinct hereditary disposition and pattern of involvement, and several hypotheses about its etiopathogenesis have been proposed. In spite of significant advances made in Th17 dynamics and AS treatment, the underlying mechanism remains concealed. To this end, we covered several topics, including the nature of the immune response, the microenvironment in the articulation that is behind the disease’s progression, and the split between the hypotheses and the evidence on how the intestine affects arthritis. In this review, we describe the current findings of AS and SpA, with the aim of providing an integrated view of the initiation of inflammation and the development of the disease.

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The Association Between HLA Genetic Susceptibility Markers and Sonographic Enthesitis in Psoriatic Arthritis

Abstract: HLA-B*27 is associated with more severe sonographic enthesitis in PsA, particularly in patients with longer disease duration. This finding highlights the possible role of genetic variants in predisposing to PsA subphenotypes.

Cited by 15 publications

References 34 publications

Revisiting the gut–joint axis: links between gut inflammation and spondyloarthritis

Revisiting the gut–joint axis: links between gut inflammation and spondyloarthritis

Defining imaging sub-phenotypes of psoriatic arthritis: integrative analysis of imaging data and gene expression in a PsA patient cohort

Joint together: The etiology and pathogenesis of ankylosing spondylitis

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