Disease-associated pathophysiologic structures in pediatric rheumatic diseases show characteristics of scale-free networks seen in physiologic systems: implications for pathogenesis and treatment

Frank, Mark Barton; Wang, Shirley; Aggarwal, Amita; Knowlton, Nicholas; Jiang, Kaiyu; Chen, Yanmin; McKee, Ryan M; Chaser, Brad; McGhee, Timothy; Osban, Jeanette; Jarvis, James N.

doi:10.1186/1755-8794-2-9

Cited by 14 publications

(18 citation statements)

References 31 publications

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“…Thus, they are an important component of the acute response to infection and tissue injury. However, in recent years, we have also demonstrated that neutrophils show transcriptional aberrations in chronic childhood inflammatory diseases, including juvenile idiopathic arthritis (JIA) [ 1 ] and juvenile dermatomysositis [ 2 ]. In JIA, these transcriptional aberrations do not correct with therapy [ 3 ] and are associated with specific perturbations in cellular metabolic function [ 1 ].…”

Section: Introductionmentioning

confidence: 99%

RNA sequencing from human neutrophils reveals distinct transcriptional differences associated with chronic inflammatory states

et al. 2015

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BackgroundThe transcriptional complexity of mammalian cells suggests that they have broad abilities to respond to specific environmental stimuli and physiologic contexts. These abilities were not apparent a priori from the structure of mammalian genomes, but have been identified through detailed transcriptome analyses. In this study, we examined the transcriptomes of cells of the innate immune system, human neutrophils, using RNA sequencing (RNAseq).MethodsWe sequenced poly-A RNA from nine individual samples corresponding to specific phenotypes: three children with active, untreated juvenile idiopathic arthritis (JIA)(AD), three children with the same disease whose disease was inactive on medication (CRM), and three children with cystic fibrosis (CF).ResultsWe demonstrate that transcriptomes of neutrophils, typically considered non-specific in their responses and functions, display considerable specificity in their transcriptional repertoires dependent on the pathologic context, and included genes, gene isoforms, and long non-coding RNA transcripts. Furthermore, despite the small sample numbers, these findings demonstrate the potential of RNAseq approaches to biomarker development in rheumatic diseases.ConclusionsThese data demonstrate the capacity of cells previously considered non-specific in function to adapt their transcriptomes to specific biologic contexts. These data also provide insight into previously unrecognized pathological pathways and show considerable promise for elucidating disease and disease-state specific regulatory networks.Electronic supplementary materialThe online version of this article (doi:10.1186/s12920-015-0128-7) contains supplementary material, which is available to authorized users.

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Section: Introductionmentioning

confidence: 99%

RNA sequencing from human neutrophils reveals distinct transcriptional differences associated with chronic inflammatory states

et al. 2015

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“…Furthermore, these transcriptional abnormalities are linked to aberrations in specific neutrophil metabolic functions 10 . Thus, although it is conventionally thought of as an autoimmune disease driven by disordered T cell responses 11 , increasing evidence points to an important role for innate immunity in the pathogenesis of JIA 10 12 13 . Furthermore, there is a growing body of data demonstrating the importance of neutrophils in shaping adaptive immune response 14 15 .…”

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Complexity and Specificity of the Neutrophil Transcriptomes in Juvenile Idiopathic Arthritis

Jiang

Frank

et al. 2016

Sci Rep

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NIH projects such as ENCODE and Roadmap Epigenomics have revealed surprising complexity in the transcriptomes of mammalian cells. In this study, we explored transcriptional complexity in human neutrophils, cells generally regarded as nonspecific in their functions and responses. We studied distinct human disease phenotypes and found that, at the gene, gene isoform, and miRNA level, neutrophils exhibit considerable specificity in their transcriptomes. Thus, even cells whose responses are considered non-specific show tailoring of their transcriptional repertoire toward specific physiologic or pathologic contexts. We also found that miRNAs had a global impact on neutrophil transcriptome and are associated with innate immunity in juvenile idiopathic arthritis (JIA). These findings have important implications for our understanding of the link between genes, non-coding transcripts and disease phenotypes.

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“…These small numbers are therefore prone to high false discovery rates that can't be completely eliminated with any bioinformatics approach. A larger patient population of untreated patients (9 girls and 8 boys) was described by Frank et al in a study aimed at discovering gene expression network structures in both JIA and JDM 51) .…”

Section: Transcription Profilingmentioning

confidence: 99%

Using proteomic and genomic methods to understand JDM

Karasawa

Jarvis

2015

Jpn. J. Clin. Immunol.

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Juvenile dermatomyositis is a complex illness characterized by vascular/perivascular inflammation, primarily in the skin and muscles. In this review, we discuss how proteomic and genomic technologies have expanded our understanding of the immune pathogenesis of this disease. We will also discuss further directions that the field may take to use existing and developing technologies to further our understanding of this often-perplexing disease.

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Disease-associated pathophysiologic structures in pediatric rheumatic diseases show characteristics of scale-free networks seen in physiologic systems: implications for pathogenesis and treatment

Cited by 14 publications

References 31 publications

RNA sequencing from human neutrophils reveals distinct transcriptional differences associated with chronic inflammatory states

RNA sequencing from human neutrophils reveals distinct transcriptional differences associated with chronic inflammatory states

Complexity and Specificity of the Neutrophil Transcriptomes in Juvenile Idiopathic Arthritis

Using proteomic and genomic methods to understand JDM

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