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Blood leukocyte microarrays to diagnose systemic onset juvenile idiopathic arthritis and follow the response to IL-1 blockade.

Allantaz F, Chaussabel D, Stichweh D, Bennett L, Allman W, Mejias A, Ardura M, Chung W, Smith E, Wise C, Palucka K, Ramilo O, Punaro M, Banchereau J, Pascual V - J. Exp. Med. (2007)

Bottom Line: Statistical group comparison and class prediction identified genes differentially expressed in SoJIA patients compared with healthy children.Transcripts that changed significantly in patients undergoing IL-1 blockade were also identified.Availability of early diagnostic markers may allow prompt initiation of therapy and prevention of disabilities.

View Article: PubMed Central - PubMed

Affiliation: Baylor National Institute of Allergy and Infectious Diseases Cooperative Center for Translational Research on Human Immunology and Biodefense, Dallas, TX 75204, USA.

ABSTRACT
Systemic onset juvenile idiopathic arthritis (SoJIA) represents up to 20% of juvenile idiopathic arthritis. We recently reported that interleukin (IL) 1 is an important mediator of this disease and that IL-1 blockade induces clinical remission. However, lack of specificity of the initial systemic manifestations leads to delays in diagnosis and initiation of therapy. To develop a specific diagnostic test, we analyzed leukocyte gene expression profiles of 44 pediatric SoJIA patients, 94 pediatric patients with acute viral and bacterial infections, 38 pediatric patients with systemic lupus erythematosus (SLE), 6 patients with PAPA syndrome, and 39 healthy children. Statistical group comparison and class prediction identified genes differentially expressed in SoJIA patients compared with healthy children. These genes, however, were also changed in patients with acute infections and SLE. An analysis of significance across all diagnostic groups identified 88 SoJIA-specific genes, 12 of which accurately classified an independent set of SoJIA patients with systemic disease. Transcripts that changed significantly in patients undergoing IL-1 blockade were also identified. Thus, leukocyte transcriptional signatures can be used to distinguish SoJIA from other febrile illnesses and to assess response to therapy. Availability of early diagnostic markers may allow prompt initiation of therapy and prevention of disabilities.

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Related in: MedlinePlus

Differential gene expression in PBMCs isolated from SoJIA patients and healthy controls. 17,454 genes passing the control criteria were tested. Genes expressed at statistically different levels between the two groups (P < 0.01; Wilcoxon-Mann-Whitney test, Bonferroni correction) were rearranged by hierarchical clustering to reveal differential expression. Expression values are normalized per gene to the healthy group. Transformed expression levels are indicated by color scale, with red representing relative high expression and blue indicating relative low expression. A list of the genes shown in this figure is available in Table S2.
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fig1: Differential gene expression in PBMCs isolated from SoJIA patients and healthy controls. 17,454 genes passing the control criteria were tested. Genes expressed at statistically different levels between the two groups (P < 0.01; Wilcoxon-Mann-Whitney test, Bonferroni correction) were rearranged by hierarchical clustering to reveal differential expression. Expression values are normalized per gene to the healthy group. Transformed expression levels are indicated by color scale, with red representing relative high expression and blue indicating relative low expression. A list of the genes shown in this figure is available in Table S2.

Mentions: To identify genes whose expression would differentiate SoJIA patients (n = 16) from healthy controls (n = 16), statistical group comparisons were performed using the nonparametric Mann-Whitney rank test (P < 0.01) and Bonferroni correction. Transcripts displaying statistically significant differences (n = 873, 398 up-regulated and 475 down-regulated) were ordered by hierarchical clustering (Fig. 1 and Table S2, which is available at http://www.jem.org/cgi/content/full/jem.20070070/DC1). The 50 most significant genes are listed in Table S2 (marked with an asterisk). The expression of some of these genes can be interpreted based on our current knowledge of the disease. Related to the frequent anemia and the presence of erythroblasts in the blood of these patients, many erythroid lineage-specific genes are found up-regulated. Likewise, neutrophil-specific genes and genes that promote neutrophil survival (i.e., Foxo3a) (27) are found overexpressed. This is consistent with the neutrophilia present in SoJIA patients. Many of the over- and underexpressed genes, however, cannot be linked to a particular cell type or function.


Blood leukocyte microarrays to diagnose systemic onset juvenile idiopathic arthritis and follow the response to IL-1 blockade.

Allantaz F, Chaussabel D, Stichweh D, Bennett L, Allman W, Mejias A, Ardura M, Chung W, Smith E, Wise C, Palucka K, Ramilo O, Punaro M, Banchereau J, Pascual V - J. Exp. Med. (2007)

Differential gene expression in PBMCs isolated from SoJIA patients and healthy controls. 17,454 genes passing the control criteria were tested. Genes expressed at statistically different levels between the two groups (P < 0.01; Wilcoxon-Mann-Whitney test, Bonferroni correction) were rearranged by hierarchical clustering to reveal differential expression. Expression values are normalized per gene to the healthy group. Transformed expression levels are indicated by color scale, with red representing relative high expression and blue indicating relative low expression. A list of the genes shown in this figure is available in Table S2.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC2118700&req=5

fig1: Differential gene expression in PBMCs isolated from SoJIA patients and healthy controls. 17,454 genes passing the control criteria were tested. Genes expressed at statistically different levels between the two groups (P < 0.01; Wilcoxon-Mann-Whitney test, Bonferroni correction) were rearranged by hierarchical clustering to reveal differential expression. Expression values are normalized per gene to the healthy group. Transformed expression levels are indicated by color scale, with red representing relative high expression and blue indicating relative low expression. A list of the genes shown in this figure is available in Table S2.
Mentions: To identify genes whose expression would differentiate SoJIA patients (n = 16) from healthy controls (n = 16), statistical group comparisons were performed using the nonparametric Mann-Whitney rank test (P < 0.01) and Bonferroni correction. Transcripts displaying statistically significant differences (n = 873, 398 up-regulated and 475 down-regulated) were ordered by hierarchical clustering (Fig. 1 and Table S2, which is available at http://www.jem.org/cgi/content/full/jem.20070070/DC1). The 50 most significant genes are listed in Table S2 (marked with an asterisk). The expression of some of these genes can be interpreted based on our current knowledge of the disease. Related to the frequent anemia and the presence of erythroblasts in the blood of these patients, many erythroid lineage-specific genes are found up-regulated. Likewise, neutrophil-specific genes and genes that promote neutrophil survival (i.e., Foxo3a) (27) are found overexpressed. This is consistent with the neutrophilia present in SoJIA patients. Many of the over- and underexpressed genes, however, cannot be linked to a particular cell type or function.

Bottom Line: Statistical group comparison and class prediction identified genes differentially expressed in SoJIA patients compared with healthy children.Transcripts that changed significantly in patients undergoing IL-1 blockade were also identified.Availability of early diagnostic markers may allow prompt initiation of therapy and prevention of disabilities.

View Article: PubMed Central - PubMed

Affiliation: Baylor National Institute of Allergy and Infectious Diseases Cooperative Center for Translational Research on Human Immunology and Biodefense, Dallas, TX 75204, USA.

ABSTRACT
Systemic onset juvenile idiopathic arthritis (SoJIA) represents up to 20% of juvenile idiopathic arthritis. We recently reported that interleukin (IL) 1 is an important mediator of this disease and that IL-1 blockade induces clinical remission. However, lack of specificity of the initial systemic manifestations leads to delays in diagnosis and initiation of therapy. To develop a specific diagnostic test, we analyzed leukocyte gene expression profiles of 44 pediatric SoJIA patients, 94 pediatric patients with acute viral and bacterial infections, 38 pediatric patients with systemic lupus erythematosus (SLE), 6 patients with PAPA syndrome, and 39 healthy children. Statistical group comparison and class prediction identified genes differentially expressed in SoJIA patients compared with healthy children. These genes, however, were also changed in patients with acute infections and SLE. An analysis of significance across all diagnostic groups identified 88 SoJIA-specific genes, 12 of which accurately classified an independent set of SoJIA patients with systemic disease. Transcripts that changed significantly in patients undergoing IL-1 blockade were also identified. Thus, leukocyte transcriptional signatures can be used to distinguish SoJIA from other febrile illnesses and to assess response to therapy. Availability of early diagnostic markers may allow prompt initiation of therapy and prevention of disabilities.

Show MeSH
Related in: MedlinePlus