The Multi-Omics Architecture of Juvenile Idiopathic Arthritis

Hou, Xin; Qu, Hui‐Qi; Zhang, Sipeng; Qi, Xiaohui; Hákonarson, Hákon; Xia, Qianghua; Li, Jin

doi:10.3390/cells9102301

Cited by 23 publications

(28 citation statements)

References 125 publications

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“…Therefore, in our study, we attempted to examine the role of the interaction between the polymorphic loci of the corresponding genes in the formation of JIA (in general), which may contribute to a deeper understanding of the disease pathogenesis, and possibly further optimization of its therapeutic strategies. The relevance of the issue was confirmed by the data on the features of immune system functioning [6][7][8][9][10]. Various intracellular and extracellular stimuli trigger a signaling cascade, in which many pathways and mediators are simultaneously involved [11,12].…”

Section: Introductionmentioning

confidence: 91%

Interaction Of Immune Response Mediator Genes In A Predisposition To Juvenile Idiopathic Arthritis

et al. 2022

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Background/objective — The goal of our study was to investigate the role of interaction between the polymorphic loci of immune response mediator genes (TNFA rs1800629, LTA rs909253, IL1B rs16944, IL2-IL21 rs6822844, IL2RA rs2104286, IL6 rs1800795, IL10 rs1800872, MIF rs755622, CTLA4 rs3087243, NFKB1 rs28362491, PTPN22 rs2476601, and PADI4 rs2240336) in the formation of a genetic predisposition to juvenile idiopathic arthritis (JIA). Material and Methods — The study involved 330 JIA patients and 342 volunteers from the Republic of Bashkortostan. Genotyping was conducted via the real-time polymerase chain reaction. The gene-gene interactions were studied using the multifactor dimensionality reduction algorithm. Results — In general analysis, the best model of gene-gene interaction in JIA was a combination of IL1B rs16944 – IL10 rs1800872 – NFKB1 rs28362491 – PADI4 rs2240336 polymorphic loci. However, after gender-based stratification the best results were obtained when examining the combinations of IL6 rs1800795 – PADI4 rs2240336 loci in girls and of IL10 rs1800872 – IL6 rs1800795 – IL2RA rs2104286 loci in boys. Within all of these models, the genotype combinations associated with both augmented and reduced JIA risks were identified (taking into account gender-specific differences). Conclusion — The results of our study implied that an important role in the formation of a predisposition to JIA is played by gene-gene interactions of IL1B rs16944, IL2RA rs2104286, IL6 rs1800795, IL10 rs1800872, NFKB1 rs28362491, and PADI4 rs2240336 polymorphic loci (taking into account gender-specific differences).

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Section: Introductionmentioning

confidence: 91%

Interaction Of Immune Response Mediator Genes In A Predisposition To Juvenile Idiopathic Arthritis

et al. 2022

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“…HLA class II alleles are remarkably associated with sJIA. HLA-DRB1*11 has a strong association, while the SNP rs151043342 has the strongest association with sJIA [ 26 ].…”

Section: Biomarkers For Diagnosis Treatment and Disease Activity In S...mentioning

confidence: 99%

Biomarkers in Systemic Juvenile Idiopathic Arthritis, Macrophage Activation Syndrome and Their Importance in COVID Era

Ailioaie

Litscher

2022

IJMS

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Systemic juvenile idiopathic arthritis (sJIA) and its complication, macrophage activation syndrome (sJIA-MAS), are rare but sometimes very serious or even critical diseases of childhood that can occasionally be characterized by nonspecific clinical signs and symptoms at onset—such as non-remitting high fever, headache, rash, or arthralgia—and are biologically accompanied by an increase in acute-phase reactants. For a correct positive diagnosis, it is necessary to rule out bacterial or viral infections, neoplasia, and other immune-mediated inflammatory diseases. Delays in diagnosis will result in late initiation of targeted therapy. A set of biomarkers is useful to distinguish sJIA or sJIA-MAS from similar clinical entities, especially when arthritis is absent. Biomarkers should be accessible to many patients, with convenient production and acquisition prices for pediatric medical laboratories, as well as being easy to determine, having high sensitivity and specificity, and correlating with pathophysiological disease pathways. The aim of this review was to identify the newest and most powerful biomarkers and their synergistic interaction for easy and accurate recognition of sJIA and sJIA-MAS, so as to immediately guide clinicians in correct diagnosis and in predicting disease outcomes, the response to treatment, and the risk of relapses. Biomarkers constitute an exciting field of research, especially due to the heterogeneous nature of cytokine storm syndromes (CSSs) in the COVID era. They must be selected with utmost care—a fact supported by the increasingly improved genetic and pathophysiological comprehension of sJIA, but also of CSS—so that new classification systems may soon be developed to define homogeneous groups of patients, although each with a distinct disease.

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“…Finally, future network analysis using multiomics approach to integrate emerging forms of data from multiple platforms, has the potential to further highlights overall imunopathogenesis of the jSpA and offer true biological classification of childhood arthritis as suggested recently (210,211).…”

Section: Putting It All Togethermentioning

confidence: 99%

Immunopathophysiology of Juvenile Spondyloarthritis (jSpA): The “Out of the Box” View on Epigenetics, Neuroendocrine Pathways and Role of the Macrophage Migration Inhibitory Factor (MIF)

Harjaček

2021

Front. Med.

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Juvenile spondyloarthritis (jSpA) is a an umbrella term for heterogeneous group of related seronegative inflammatory disorders sharing common symptoms. Although it mainly affects children and adolescents, it often remains active during adulthood. Genetic and environmental factors are involved in its occurrence, although the exact underlying immunopathophysiology remains incompletely elucidated. Accumulated evidence suggests that, in affected patients, subclinical gut inflammation caused by intestinal dysbiosis, is pivotal to the future development of synovial–entheseal complex inflammation. While the predominant role of IL17/23 axis, TNF-α, and IL-7 in the pathophysiology of SpA, including jSpA, is firmly established, the role of the cytokine macrophage migration inhibitory factor (MIF) is generally overlooked. The purpose of this review is to discuss and emphasize the role of epigenetics, neuroendocrine pathways and the hypothalamic-pituitary (HPA) axis, and to propose a novel hypothesis of the role of decreased NLRP3 gene expression and possibly MIF in the early phases of jSpA development. The decreased NLRP3 gene expression in the latter, due to hypomethylation of promotor site, is (one of) the cause for inflammasome malfunction leading to gut dysbiosis observed in patients with early jSpA. In addition, we highlight the role of MIF in the complex innate, adaptive cellular and main effector cytokine network, Finally, since treatment of advanced bone pathology in SpA remains an unmet clinical need, I suggest possible new drug targets with the aim to ultimately improve treatment efficacy and long-term outcome of jSpA patients.

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The Multi-Omics Architecture of Juvenile Idiopathic Arthritis

Cited by 23 publications

References 125 publications

Interaction Of Immune Response Mediator Genes In A Predisposition To Juvenile Idiopathic Arthritis

Interaction Of Immune Response Mediator Genes In A Predisposition To Juvenile Idiopathic Arthritis

Biomarkers in Systemic Juvenile Idiopathic Arthritis, Macrophage Activation Syndrome and Their Importance in COVID Era

Immunopathophysiology of Juvenile Spondyloarthritis (jSpA): The “Out of the Box” View on Epigenetics, Neuroendocrine Pathways and Role of the Macrophage Migration Inhibitory Factor (MIF)

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