New developments in our understanding of ankylosing spondylitis pathogenesis

Voruganti, Aniruddha; Bowness, Paul

doi:10.1111/imm.13242

Cited by 69 publications

(54 citation statements)

References 89 publications

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“…AS is a complex disease that involves many factors (6). For patients with AS, there is currently no complete cure.…”

Section: Discussionmentioning

confidence: 99%

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Bioinformatics Analysis of the Molecular Mechanism and Potential Treatment Target of Ankylosing Spondylitis

Meng

et al. 2021

Computational and Mathematical Methods in Medicine

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Ankylosing spondylitis (AS) is an autoimmune disease that mainly affects the spinal joints, sacroiliac joints, and adjacent soft tissues. We conducted bioinformatics analysis to explore the molecular mechanism related to AS pathogenesis and uncover novel potential molecular targets for the treatment of AS. The profiles of GSE25101, containing gene expression data extracted from the blood of 16 AS patients and 16 matched controls, were acquired from the Gene Expression Omnibus (GEO) database. The background correction and standardization were carried out utilizing the transcript per million (TPM) method. After analysis of AS patients and the normal groups, we identified 199 differentially expressed genes (DEGs) with upregulation and 121 DEGs with downregulation by the limma R package. The results of the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway and Gene Ontology (GO) biological process enrichment analysis revealed that the DEGs with upregulation were mainly associated with spliceosome, ribosome, RNA-catabolic process, electron transport chain, etc. And the DEGs with downregulation primarily participated in T cell-associated pathways and processes. After analysis of the protein-protein interaction (PPI) network, our data revealed that the hub genes, comprising MRPL13, MRPL22, LSM3, COX7A2, COX7C, EP300, PTPRC, and CD4, could be the treatment targets in AS. Our data furnish new hints to uncover the features of AS and explore more promising treatment targets towards AS.

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“…AS is a complex disease that involves many factors (6). For patients with AS, there is currently no complete cure.…”

Section: Discussionmentioning

confidence: 99%

“…It is only understood that genetic factors play major roles in AS pathogenesis (5). Besides, environmental, immune, metabolic, and other factors are also common causes of AS (6). Presently, AS cannot be completely cured.…”

Section: Introductionmentioning

confidence: 99%

Bioinformatics Analysis of the Molecular Mechanism and Potential Treatment Target of Ankylosing Spondylitis

Meng

et al. 2021

Computational and Mathematical Methods in Medicine

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“…In our study, one AS patient's HLA-B*27 subtyping was negative, which suggests that other pathogenic agents may also be involved in the pathogenesis of AS, such as aminopeptidase gene, IL-23R, Type 17 immunity, intergenic regions and gut microbiom. [35][36][37]…”

Section: Discussionmentioning

confidence: 99%

Predominant frequency of HLA‐B*27 in patients with ankylosing spondylitis in southeastern China

Yang

Dong

et al. 2021

Immunity Inflam & Disease

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Objectives: This study was to investigate the polymorphism and distribution of alleles of HLA-B*27 in patients with ankylosing spondylitis (AS) in Han population of southeastern China. Methods: A total of 89 peripheral blood samples from southeastern Chinese Han patients with AS that diagnosed according to Modified New York criteria were subtyped using the high-resolution PCR-SSP.Exon 2-3 of HLA-B*27 gene was amplified and sequenced to further confirm the HLA-B*27 subtype. Results: The frequency of HLA-B*27 was 99.87% in AS patients. Three subtypes, HLA-B*2704, HLA-B*2705, and HLA-B*2706 were identified. The frequencies for these three alleles were HLA-B*2704 in 84/88 (95.46%), HLA-B*2705 in 3/88(3.41%), and HLA-B*2706 in 1/88 (1.13%) of the HLA-B*27 positive patients, respectively. Conclusions: Our study shows that HLA-B*2704 has an overwhelming frequency in southeastern Chinese Han AS patients. A combined analysis including previous studies of HLA-B*27-subtype distributions in Chinese Han populations showed that HLA-B*2704 may originate from the southern Han and then migrate and spread to the northern areas, and HLA-B*2705 show the opposite result.

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“…With regard to the pathogenesis of SpA, JAKs are involved in the signaling of key cytokines within the IL-23/IL-17 pathway, and Genome-wide association studies have found single nucleotide polymorphisms (SNPs) for IL23R, JAK2, and TYK2 in ankylosing spondylitis (AS) (11). IL-23, produced by activated myeloid cells, is important for the generation of IL-17 and IL-22 by target cells such as T helper cells 17 (Th17), gamma delta T cells (γδ T cells), or innate lymphoid cells (ILCs) type 3 (12). A combination of JAK2 and TYK2 transmits the IL-23 signal via STAT3 and, to a lesser extent, STAT4 (6,13).…”

Section: Janus Kinase and Signal Transducer And Activator Of Transcrimentioning

confidence: 99%

Impact of Janus Kinase Inhibition on the Treatment of Axial Spondyloarthropathies

2020

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Many immune cells and effector molecules (e.g. cytokines, Interferons, growth factors) utilize different combinations of Janus kinase (JAK) and signal transducer and activator of transcription (STAT) molecules to transduce signals from the cell surface to the nucleus, where they regulate transcription. This pathway is basically involved in almost all inflammatory diseases and also in the interleukin (IL)-23/IL-17 cascade, which is an essential part of the pathogenesis of spondyloarthropathies (SpA). Upon evidence from in vitro and in vivo experiments indicating disease-modifying effects of JAK inhibition in inflammatory joint disease, numerous inhibitors of the JAK/STAT pathway (= JAKinibs) with different selectivity against the four members of the JAK family [JAK1, JAK2, JAK3, and tyrosine kinase 2 (TYK2)] were developed. Trials in rheumatoid arthritis were successful with respect to efficacy and safety, and currently, three JAKinibs are approved for the treatment of rheumatoid arthritis in the European Union. Although new treatment options (anti-IL-23, anti-IL-17, and phosphodiesterase 4 inhibitors) have become available for spondyloarthritis and especially psoriatic arthritis (PsA) within the last years, most of them are biologics and do not address all disease manifestations equally. Therefore, multiple trials were initiated to evaluate JAKinibs in PsA and axial spondyloarthritis (axSpA). A trial of Tofacitinib (OPAL) was successful in PsA and has led to the inclusion of JAKinibs into the treatment algorithm. Currently many trials with JAKinibs are ongoing for PsA and axSpA, with one phase III trial of upadacitinib (selective JAK1 inhibitor) showing good therapeutic response in active radiographic axSpA.

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New developments in our understanding of ankylosing spondylitis pathogenesis

Cited by 69 publications

References 89 publications

Bioinformatics Analysis of the Molecular Mechanism and Potential Treatment Target of Ankylosing Spondylitis

Bioinformatics Analysis of the Molecular Mechanism and Potential Treatment Target of Ankylosing Spondylitis

Predominant frequency of HLA‐B*27 in patients with ankylosing spondylitis in southeastern China

Impact of Janus Kinase Inhibition on the Treatment of Axial Spondyloarthropathies

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