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Blood Leukocyte Microarrays to Diagnose Systemic Onset Juvenile Idiopathic Arthritis and Follow IL-1 blocade

ABSTRACT: Systemic onset Juvenile Idiopathic Arthritis (SoJIA) represents up to 20% of Juvenile Idiopathic Arthritis (JIA). We have previously reported that this disease is Interleukin 1 (IL1)-mediated, and that IL-1 blockade results in clinical remission in the majority of patients. The diagnosis of SoJIA, however, still relies on clinical findings as no specific diagnostic tests are available, which leads to delays in the initiation of specific therapy. To identify specific diagnostic markers, we analyzed gene expression profiles in 19 pediatric patients with SoJIA during the systemic phase of the disease (fever and/or arthritis), 25 SoJIA patients with no systemic symptoms (arthritis only or no symptoms), 39 healthy controls, 94 pediatric patients with acute viral and bacterial infections (available under GSE6269), 38 pediatric patients with Systemic Lupus Erythematosus (SLE), and 6 patients with a second IL-1 mediated disease known as PAPA syndrome. Statistical group comparison and class prediction identified genes differentially expressed in SoJIA patients compared to healthy children. These genes, however, were also changed in patients with acute infections and SLE. By performing an analysis of significance across all diagnostic groups, we generated a list of 88 SoJIA-specific genes (p<0.01 in SoJIA and >0.5 in all other groups). A subset of 12/88 genes permitted us to accurately classify an independent test set of SoJIA patients with systemic disease. We were also able to identify a group of transcripts that changed significantly in patients undergoing IL-1 blockade. Thus, analysis of transcriptional signatures from SoJIA blood leukocytes can help distinguishing this disease from other febrile illnesses and assessing response to therapy. Availability of accurate diagnostic markers for SoJIA patients may allow prompt initiation of effective therapy and prevention of long-term disabilities. Keywords: Disease state analysis

ORGANISM(S): Homo sapiens

PROVIDER: GSE8650 | GEO | 2007/09/01

SECONDARY ACCESSION(S): PRJNA101841

REPOSITORIES: GEO

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Project description:Systemic onset Juvenile Idiopathic Arthritis (SoJIA) represents up to 20% of Juvenile Idiopathic Arthritis (JIA). We have previously reported that this disease is Interleukin 1 (IL1)-mediated, and that IL-1 blockade results in clinical remission in the majority of patients. The diagnosis of SoJIA, however, still relies on clinical findings as no specific diagnostic tests are available, which leads to delays in the initiation of specific therapy. To identify specific diagnostic markers, we analyzed gene expression profiles in 19 pediatric patients with SoJIA during the systemic phase of the disease (fever and/or arthritis), 25 SoJIA patients with no systemic symptoms (arthritis only or no symptoms), 39 healthy controls, 94 pediatric patients with acute viral and bacterial infections (available under GSE6269), 38 pediatric patients with Systemic Lupus Erythematosus (SLE), and 6 patients with a second IL-1 mediated disease known as PAPA syndrome. Statistical group comparison and class prediction identified genes differentially expressed in SoJIA patients compared to healthy children. These genes, however, were also changed in patients with acute infections and SLE. By performing an analysis of significance across all diagnostic groups, we generated a list of 88 SoJIA-specific genes (p<0.01 in SoJIA and >0.5 in all other groups). A subset of 12/88 genes permitted us to accurately classify an independent test set of SoJIA patients with systemic disease. We were also able to identify a group of transcripts that changed significantly in patients undergoing IL-1 blockade. Thus, analysis of transcriptional signatures from SoJIA blood leukocytes can help distinguishing this disease from other febrile illnesses and assessing response to therapy. Availability of accurate diagnostic markers for SoJIA patients may allow prompt initiation of effective therapy and prevention of long-term disabilities. Keywords: Disease state analysis 123 RNA samples extracted from PBMCs were studied. For more details on the clinical information, please refer to the paper (PudMed ID...).

Project description:Objective: A multi-center study of recent onset juvenile idiopathic arthritis (JIA) subjects prior to treatment with DMARDS or biologics was undertaken to identify peripheral blood gene expression differences between JIA subclasses and controls. Methods: PBMC from 59 healthy children and 136 JIA subjects (28 enthesitis-related arthritis[ERA], 42 persistent oligoarthritis, 45 RF- polyarthritis, and 21 systemic) were isolated on Ficoll. Poly-A RNA was labeled using NuGEN Ovation and gene expression profiles were obtained using Affymetrix HG-U133 plus 2.0 Arrays. Results: 9,501 differentially expressed probe sets were identified among JIA subtypes and controls (ANOVA, FDR 5%). Specifically, 193, 1036, 873 and 7595 probe sets were different between controls and ERA, persistent oligoarthritis, RF- polyarthritis and systemic JIA samples respectively. In persistent oligoarthritis, RF- polyarthritis and systemic JIA subtypes, up-regulation of gene associated with IL-10 signaling was prominent. A hemoglobin cluster was identified that was under-expressed in ERA patients but over-expressed in systemic JIA. The influence of JAK/STAT, ERK/MAPK, IL-2 and B cell receptor signaling pathways was evident in persistent oligoarthritis. In systemic JIA, up regulation of innate immune pathways, including IL-6, TLR/IL1R, and PPAR signaling were noted, along with down regulation of gene networks related to NK and T cells. Complement and coagulation pathways were up-regulated in systemic JIA with a subset of these components differentially-expressed in the other three subtypes. Conclusions: Expression analysis identified differentially expressed genes in PBMCs between subclasses of JIA early in disease and controls, thus providing evidence for immunobiologic differences between these forms of childhood arthritis. Keywords: Gene expression. PBMC. Patients compared with controls. PBMC from 59 healthy children and 136 JIA subjects (28 enthesitis-related arthritis[ERA], 42 persistent oligoarthritis, 45 RF- polyarthritis, and 21 systemic) were isolated on Ficoll. Poly-A RNA was labeled using NuGEN Ovation and gene expression profiles were obtained using Affymetrix HG-U133 plus 2.0 Arrays

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Blood Leukocyte Microarrays to Diagnose Systemic Onset Juvenile Idiopathic Arthritis and Follow IL-1 blocade

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