Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Understanding the Pathogenesis of Spondyloarthritis.

ABSTRACT: Spondyloarthritis comprises a group of inflammatory diseases of the joints and spine, with various clinical manifestations. The group includes ankylosing spondylitis, reactive arthritis, psoriatic arthritis, arthritis associated with inflammatory bowel disease, and undifferentiated spondyloarthritis. The exact etiology and pathogenesis of spondyloarthritis are still unknown, but five hypotheses explaining the pathogenesis exist. These hypotheses suggest that spondyloarthritis is caused by arthritogenic peptides, an unfolded protein response, HLA-B*27 homodimer formation, malfunctioning endoplasmic reticulum aminopeptidases, and, last but not least, gut inflammation and dysbiosis. Here we discuss the five hypotheses and the evidence supporting each. In all of these hypotheses, HLA-B*27 plays a central role. It is likely that a combination of these hypotheses, with HLA-B*27 taking center stage, will eventually explain the development of spondyloarthritis in predisposed individuals.

SUBMITTER: Sharip A

PROVIDER: S-EPMC7588965 | biostudies-literature | 2020 Oct

REPOSITORIES: biostudies-literature

ACCESS DATA

Json Xml

Publications

Understanding the Pathogenesis of Spondyloarthritis.

Sharip Aigul A Kunz Jeannette J

Biomolecules 20201020 10

Spondyloarthritis comprises a group of inflammatory diseases of the joints and spine, with various clinical manifestations. The group includes ankylosing spondylitis, reactive arthritis, psoriatic arthritis, arthritis associated with inflammatory bowel disease, and undifferentiated spondyloarthritis. The exact etiology and pathogenesis of spondyloarthritis are still unknown, but five hypotheses explaining the pathogenesis exist. These hypotheses suggest that spondyloarthritis is caused by arthri ...[more]

PMID: 33092023

Similar Datasets

New advances in the understanding and treatment of axial spondyloarthritis: from chance to choice.

Project description:Axial spondyloarthritis (axSpA) is a chronic inflammatory condition that encompasses ankylosing spondylitis (AS) as well as non-radiographic axial disease (nr-axSpA) and can lead to chronic pain, structural damage and disability. The introduction of tumour necrosis factor inhibitor (TNFi) drugs for AS heralded a new era of drug therapeutics for what was previously a largely untreatable disease. This has now been expanded with the licensing of secukinumab, an interleukin 17A (IL-17A) inhibitor for the treatment of AS. Although biologic disease modifying antirheumatic drugs (bDMARDs) are not a first line treatment option in AS or axSpA, they are highly effective following incomplete or no response to physiotherapy and non-steroidal anti-inflammatory drugs (NSAIDs). Current research strategies aim to test whether the desired treatment goal of disease remission may now be achievable with early and stratified use of bDMARDs in both AS and nr-axSpA. This review summarizes the current literature on axSpA including pathophysiology, treatment indications, radiographic progression and the evidence for new developments in the treatment of both AS and nr-axSpA.

| S-EPMC5833172 | biostudies-other

Understanding the pathogenesis of abdominal aortic aneurysms.

Project description:An aortic aneurysm is a dilatation in which the aortic diameter is ?3.0 cm. If left untreated, the aortic wall continues to weaken and becomes unable to withstand the forces of the luminal blood pressure resulting in progressive dilatation and rupture, a catastrophic event associated with a mortality of 50-80%. Smoking and positive family history are important risk factors for the development of abdominal aortic aneurysms (AAA). Several genetic risk factors have also been identified. On the histological level, visible hallmarks of AAA pathogenesis include inflammation, smooth muscle cell apoptosis, extracellular matrix degradation and oxidative stress. We expect that large genetic, genomic, epigenetic, proteomic and metabolomic studies will be undertaken by international consortia to identify additional risk factors and biomarkers, and to enhance our understanding of the pathobiology of AAA. Collaboration between different research groups will be important in overcoming the challenges to develop pharmacological treatments for AAA.

| S-EPMC4829576 | biostudies-literature

Current Understanding of Asthma Pathogenesis and Biomarkers.

Project description:Asthma is a heterogeneous lung disease with variable phenotypes (clinical presentations) and distinctive endotypes (mechanisms). Over the last decade, considerable efforts have been made to dissect the cellular and molecular mechanisms of asthma. Aberrant T helper type 2 (Th2) inflammation is the most important pathological process for asthma, which is mediated by Th2 cytokines, such as interleukin (IL)-5, IL-4, and IL-13. Approximately 50% of mild-to-moderate asthma and a large portion of severe asthma is induced by Th2-dependent inflammation. Th2-low asthma can be mediated by non-Th2 cytokines, including IL-17 and tumor necrosis factor-α. There is emerging evidence to demonstrate that inflammation-independent processes also contribute to asthma pathogenesis. Protein kinases, adapter protein, microRNAs, ORMDL3, and gasdermin B are newly identified molecules that drive asthma progression, independent of inflammation. Eosinophils, IgE, fractional exhaled nitric oxide, and periostin are practical biomarkers for Th2-high asthma. Sputum neutrophils are easily used to diagnose Th2-low asthma. Despite progress, more studies are needed to delineate complex endotypes of asthma and to identify new and practical biomarkers for better diagnosis, classification, and treatment.

| S-EPMC9454904 | biostudies-literature

Current understanding on the pathogenesis of polyglutamine diseases.

Project description:Polyglutamine (polyQ) diseases are a family of neurodegenerative disorders including Huntington's disease, spinobulbar muscular atrophy, dentatorubral-pallidoluysian atrophy and several spinocerebellar ataxias. polyQ diseases are caused by abnormal expansion of CAG repeats in certain genes. The expanded CAG repeats are then translated into a series of abnormally expanded polyQ tracts. Such polyQ tracts may induce misfolding of the disease-causing proteins. The present review mainly focuses on the common characteristics of the pathogenesis of these polyQ diseases, including conformational transition of proteins and its influence on the function of these proteins, the correlation between decreased ability of proteolysis and late-onset polyQ diseases, and the relationship between wide expression of disease-causing proteins and selective neuronal death.

| S-EPMC5552486 | biostudies-other

Understanding flare in axial spondyloarthritis: novel insights from daily self-reported flare experience.

Project description:ObjectivesOur objective was to explore daily self-reported experiences of axial SpA (axSpA) flare based on data entered into the Project Nightingale smartphone app (www.projectnightingale.org), between 5 April 2018 and 1 April 2020.MethodsPaired t-tests were conducted for mean_flare_on and mean_flare_off scores for each recorded variable. The mean estimated difference between flare and non-flare values for each variable was calculated with 95% CIs. Mean, S.d. and range were reported for flare duration and frequency. Participants with ≥10 days of data entry were included for affinity propagation cluster analysis. Baseline characteristics and mean flare on vs mean flare off values were reported for each cluster. Welch's t-test was used to assess differences between clusters.ResultsA total of 143/189 (75.7%) participants recorded at least one flare. Each flare lasted a mean of 4.30 days (S.d. 6.82, range 1-78), with a mean frequency of once every 35.32 days (S.d. 65.73, range 1-677). Significant relationships were identified between flare status and variable scores. Two clusters of participants were identified with distinct flare profiles. Group 1 experienced less severe worsening of symptoms during flare in comparison to group 2 (P < 0.01). However, they experienced significantly longer flare duration (7.2 vs 3.5 days; P < 0.01), perhaps indicating a prolonged, yet less intense flare experience. Groups were similar in terms of flare frequency and clinical characteristics.ConclusionsTwo clusters of participants were identified with distinct flare experiences but similar baseline clinical characteristics. Smartphone technologies capture subtle changes in disease experience not currently considered in clinical practice.

| S-EPMC8678434 | biostudies-literature

The Role of the IL-23/IL-17 Pathway in the Pathogenesis of Spondyloarthritis.

Project description:Spondyloarthritis (SpA) is a subset of seronegative rheumatic-related autoimmune diseases that consist of ankylosing spondylitis (AS), psoriatic spondylitis (PsA), reactive spondylitis (re-SpA), inflammatory bowel disease (IBD)-associated spondylitis, and unclassifiable spondylitis. These subsets share clinical phenotypes such as joint inflammation and extra-articular manifestations (uveitis, IBD, and psoriasis [Ps]). Inflammation at the enthesis, where ligaments and tendons attach to bones, characterizes and distinguishes SpA from other types of arthritis. Over the past several years, genetic, experimental, and clinical studies have accumulated evidence showing that the IL-23/IL-17 axis plays a critical role in the pathogenesis of SpA. These discoveries include genetic association and the identification of IL-23- and IL-17-producing cells in the tissue of mouse models and human patients. In this review, we summarize the current knowledge of the pathomechanism by focusing on the IL-23/IL-17 pathway and examine the recent clinical studies of biological agents targeting IL-23 and IL-17 in the treatment of SpA.

| S-EPMC7504446 | biostudies-literature

Understanding the role of EZH2 insufficiency in the pathogenesis of PMF

Project description:This SuperSeries is composed of the SubSeries listed below. Refer to individual Series

2015-06-04 | E-GEOD-69500 | biostudies-arrayexpress

A qualitative exploration of the patient journey in axial spondyloarthritis towards a people-centered understanding.

Project description:This exploratory qualitative study aims to gain a people-centered understanding of the patient journey in axial spondyloarthritis (axSpA). Semi-structured interviews were conducted with 15 individuals diagnosed with axSpA, aged 18 years and older, who were purposively recruited from a rheumatologic practice in southern Germany. The interviews were carried out as web-based video calls between September and October 2021, audio-recorded, transcribed verbatim, and analyzed according to Kuckartz's qualitative content analysis. Patient journey narratives encompassed both healthcare journeys and personal journeys. Healthcare journeys were characterized as fragmented and difficult to navigate, with diagnosis often marking a turning point toward more coordinated care. Post-diagnosis, new challenges emerged (e.g., time management for treatment). Personal journeys comprised perceptions of axSpA in social contexts (e.g., stigmatization) and the continuous interplay of comorbidities and biographical events with healthcare related to axSpA. This study proposes a people-centered perspective on the patient journey in axSpA, emphasizing the interplay of biographies, comorbidities, and social context with healthcare events. Recognizing these personal factors in clinical practice is encouraged to address complex health needs and tailor treatment to each individual. Further efforts should promote collaboration between medical disciplines and integrate healthcare and social support at all stages of the axSpA patient journey.

| S-EPMC11358462 | biostudies-literature

Current Understanding of the Pathogenesis of Porcine Circovirus 3.

Project description:Circoviruses are closed, circular, single-stranded DNA viruses belonging to the family Circoviridae and the genus Circovirus. To date, at least four porcine circoviruses (PCVs) have been recognized, including PCV1 to PCV4, respectively. Similar to PCV2 pathogenesis, PCV3 has been reported worldwide with myriad clinical and pathological presentations such as reproductive disorders, respiratory diseases, diarrhea etc. Current understanding of PCV3 pathogenesis is very limited since the majority of studies were mostly field observations. Interpretation of the results from such studies is not always simple. Various confounding factors affect the clinical appearance and pathological changes of the infected pigs. Recently, several experimental PCV3 infection studies have been reported, providing a better understanding of its pathogenesis. In this review, we focused on novel findings regarding PCV3 pathogenesis from both field observation and experimental infection studies. Possible factors involved in the conflicting results among the experimental infection studies are also discussed. This review article provides important insight into the current knowledge on PCV3 pathogenesis which would aid in prioritizing research in order to fill the knowledge gaps.

| S-EPMC8778431 | biostudies-literature