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Neutrophils: the forgotten cell in JIA disease pathogenesis.

Jarvis JN, Jiang K, Petty HR, Centola M - Pediatr Rheumatol Online J (2007)

Bottom Line: However, systems biology approaches to this family of diseases have suggested complex interactions between innate and adaptive immunity that underlie JIA.In particular, new data suggest an important role for neutrophils in JIA pathogenesis.Above all else, we invite the reader to re-consider the use of the term "autoimmunity" as applied to the family of illnesses we collectively call JIA.

View Article: PubMed Central - HTML - PubMed

Affiliation: Department of Pediatrics, University of Oklahoma College of Medicine, Oklahoma City, OK 73014, USA. james-jarvis@ouhsc.edu

ABSTRACT
Juvenile idiopathic arthritis (JIA) has long been assumed to be an autoimmune disease, triggered by aberrant recognition of "self" antigens by T-cells. However, systems biology approaches to this family of diseases have suggested complex interactions between innate and adaptive immunity that underlie JIA. In particular, new data suggest an important role for neutrophils in JIA pathogenesis. In this short review, we will discuss the new data that support a role for neutrophils in JIA, discuss regulatory functions that link neutrophils to adaptive immune responses, and discuss future areas of investigation. Above all else, we invite the reader to re-consider the use of the term "autoimmunity" as applied to the family of illnesses we collectively call JIA.

No MeSH data available.


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In silico modeling derived from Pathway Assist software analysis of differential gene expression in JRA neutrophils compared with healthy control subjects. Note clusters of IFNγ-(lower right) and IL-8- (lower left) regulated genes. From Jarvis et al, Arthritis Res Therapy 2006. The authors retain the copyright for this material.
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Figure 3: In silico modeling derived from Pathway Assist software analysis of differential gene expression in JRA neutrophils compared with healthy control subjects. Note clusters of IFNγ-(lower right) and IL-8- (lower left) regulated genes. From Jarvis et al, Arthritis Res Therapy 2006. The authors retain the copyright for this material.

Mentions: We next performed gene expression profiling on neutrophils of 25 children with JRA, 15 of whom were studied during periods of active and inactive disease as defined by Wallace and colleagues [47]. In that study, we demonstrated aberrant patterns of gene expression in neutrophils of children with polyarticular JIA, even when their disease was inactive [48]. Indeed, hierachical clustering analysis, a method for asking, "Which group is most like the other group?"scattered patients with active and inactive disease indistinguishably, as shown in Figure 2. Even more interesting were in silico models of the differentially-expressed genes (Figure 3), which showed clusters of IFNγ and IL-8-related genes, the significance of which will be explained shortly. Subsequent work from our laboratory has shown that these expression abnormalities persist even when children fit consensus criteria for remission (unpublished data). This contrasts with what we have reported in peripheral blood mononuclear cells of children with JIA, where gene expression profiles normalize after therapy [49]. The obvious question is, "What is this defect, and what can we do about it?"


Neutrophils: the forgotten cell in JIA disease pathogenesis.

Jarvis JN, Jiang K, Petty HR, Centola M - Pediatr Rheumatol Online J (2007)

In silico modeling derived from Pathway Assist software analysis of differential gene expression in JRA neutrophils compared with healthy control subjects. Note clusters of IFNγ-(lower right) and IL-8- (lower left) regulated genes. From Jarvis et al, Arthritis Res Therapy 2006. The authors retain the copyright for this material.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC1904449&req=5

Figure 3: In silico modeling derived from Pathway Assist software analysis of differential gene expression in JRA neutrophils compared with healthy control subjects. Note clusters of IFNγ-(lower right) and IL-8- (lower left) regulated genes. From Jarvis et al, Arthritis Res Therapy 2006. The authors retain the copyright for this material.
Mentions: We next performed gene expression profiling on neutrophils of 25 children with JRA, 15 of whom were studied during periods of active and inactive disease as defined by Wallace and colleagues [47]. In that study, we demonstrated aberrant patterns of gene expression in neutrophils of children with polyarticular JIA, even when their disease was inactive [48]. Indeed, hierachical clustering analysis, a method for asking, "Which group is most like the other group?"scattered patients with active and inactive disease indistinguishably, as shown in Figure 2. Even more interesting were in silico models of the differentially-expressed genes (Figure 3), which showed clusters of IFNγ and IL-8-related genes, the significance of which will be explained shortly. Subsequent work from our laboratory has shown that these expression abnormalities persist even when children fit consensus criteria for remission (unpublished data). This contrasts with what we have reported in peripheral blood mononuclear cells of children with JIA, where gene expression profiles normalize after therapy [49]. The obvious question is, "What is this defect, and what can we do about it?"

Bottom Line: However, systems biology approaches to this family of diseases have suggested complex interactions between innate and adaptive immunity that underlie JIA.In particular, new data suggest an important role for neutrophils in JIA pathogenesis.Above all else, we invite the reader to re-consider the use of the term "autoimmunity" as applied to the family of illnesses we collectively call JIA.

View Article: PubMed Central - HTML - PubMed

Affiliation: Department of Pediatrics, University of Oklahoma College of Medicine, Oklahoma City, OK 73014, USA. james-jarvis@ouhsc.edu

ABSTRACT
Juvenile idiopathic arthritis (JIA) has long been assumed to be an autoimmune disease, triggered by aberrant recognition of "self" antigens by T-cells. However, systems biology approaches to this family of diseases have suggested complex interactions between innate and adaptive immunity that underlie JIA. In particular, new data suggest an important role for neutrophils in JIA pathogenesis. In this short review, we will discuss the new data that support a role for neutrophils in JIA, discuss regulatory functions that link neutrophils to adaptive immune responses, and discuss future areas of investigation. Above all else, we invite the reader to re-consider the use of the term "autoimmunity" as applied to the family of illnesses we collectively call JIA.

No MeSH data available.


Related in: MedlinePlus