We performed a phase I/II, randomized, double-blind, placebo-controlled dose-escalation study to examine the safety, immunogenicity, and biological effects of active immunization with interferon alpha-Kinoid (IFN-K) in systemic lupus erythematosus (SLE) patients. Women 18-50 years of age with mild to moderate SLE were immunized with three (n=10) or four doses (n=9) of 30, 60, 120, 240 microgram IFN-K or saline.
Down-regulation of interferon signature in systemic lupus erythematosus patients by active immunization with interferon α-kinoid.
Sex, Age, Specimen part, Disease, Disease stage, Treatment, Race
View SamplesThis SuperSeries is composed of the SubSeries listed below.
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Sex, Age, Specimen part, Disease, Disease stage, Treatment, Subject, Time
View SamplesPurpose. Temporal and local fluctuations in oxygen levels observed within tumors represent stressful conditions requiring adaptive mechanisms that provide tumor cells with phenotypic alterations to survive and proliferate in this hostile environment. The analysis of the transcriptome associated with such cycling hypoxia could thus represent a prognostic biomarker of cancer progression. Patients and Methods. We exposed 20 cell lines derived from various tissues to repeated periods of hypoxia/reoxygenation in order to determine a transcriptomic signature of cycling hypoxia (CycHyp). We then used clinical data sets from 2,150 patients with primary breast cancer to estimate a prognostic Cox proportional hazard model and to assess the prognostic performance of the CycHyp signature on independent samples. Results. The prognostic potential of the CycHyp signature was validated in patients independently of the receptor status of the tumors (HR=1.97; p = 1.8e-12). The discriminating capacity of the CycHyp signature was further increased in the ER+ HER2- patient populations (HR = 2.34, p = 9e-12) including those with a node negative status receiving or not a treatment (HR = 3.32 and 5.51; p= 5.61e-10 and 8.15e-11, respectively). We also documented the capacity of the CycHyp signature to outperform existing prognostic gene signatures with significantly higher BCR and concordance index. We also showed that the CycHyp signature could identify ER-positive node-negative breast cancer patients at high risk based on conventional clinico-pathologic criteria but who could have been spared from chemotherapy and inversely those patients classified at low risk based on the same criteria but who presented a negative outcome. Conclusion. This study demonstrates that a gene signature derived from the transcriptomic adaptation of tumor cells to cycling hypoxia is prognostic of breast cancer and offers a unique decision making tool to complement the discrimination of breast cancer patients based on anatomo-pathological evaluation. The prognostic value of CycHyp further confirms the link between cycling hypoxia and cancer progression, and thereby paves the way for a broad applicability to evaluate cancer patient outcomes.
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Specimen part, Cell line, Treatment
View SamplesInterferon-alpha Kinoid (IFN-K) is a therapeutic vaccine composed of IFN-alpha2b coupled to a carrier protein. In a phase I/II placebo-controlled trial, we observed that IFN-K significantly decreases the IFN gene signature in whole blood RNA samples from SLE patients (see GSE39088). Here, we analyzed extended follow-up data from IFN-K-treated patients, in terms of persistence of neutralizing anti-IFN Abs, gene expression profiling and safety.
Interferon α kinoid induces neutralizing anti-interferon α antibodies that decrease the expression of interferon-induced and B cell activation associated transcripts: analysis of extended follow-up data from the interferon α kinoid phase I/II study.
Sex, Specimen part, Disease, Disease stage, Subject, Time
View SamplesRheumatoid arthritis (RA) is a chronic, systemic autoimmune inflammatory disease that is characterized by the presence of inflammatory cytokines, including interleukin-6 (IL-6). Here, we investigated the global molecular effects of Tocilizumab, an approved humanized anti-IL6 Receptor antibody, versus Methotrexate therapy, in synovial biopsy samples collected prospectively in early RA before and 12 weeks after administration of the drug. The results were compared with our previous data, generated in prospective cohorts of Adalimumab- and Rituximab-treated (Methotrexate- and anti-TNF-resistant, respectively) RA patients.
Global molecular effects of tocilizumab therapy in rheumatoid arthritis synovium.
Sex, Age
View SamplesSystemic sclerosis is a connective tissue disease affecting skin and internal organs, characterized by a triad of inflammation, vasculopathy and progressive fibrosis, due to deposition of mainly type I collagen. Out of the intricate mechanisms involved in the pathogenesis of the disease, evidence indicates that TGFbeta signaling plays a central role in mediating the effects of several pro-fibrotic effectors. In addition, TGFbeta is induced by hypoxia in cultured fibroblasts, an observation suggesting a role for this cytokine in linking vasculopathy and fibrosis in the disease. Not surprisingly, TGFbeta and Wnt signaling are among the most prevalent pathways found in global gene expression studies performed on systemic sclerosis skin biopsies. In this perspective, modulation of TGFbeta activity remains a top therapeutic target in systemic sclerosis drug development.
No associated publication
Sex, Age, Specimen part, Disease, Disease stage, Treatment
View SamplesPatients with systemic lupus erythematosus are characterized by the spontaneous over-expression of interferon(IFN)-induced genes in peripheral blood RNA samples. In the present study, we wanted to study the evolution of the IFN gene signature in the peripheral blood of patients with lupus nephritis, before and after initiation of immunosuppressive therapy.
Interferon α kinoid induces neutralizing anti-interferon α antibodies that decrease the expression of interferon-induced and B cell activation associated transcripts: analysis of extended follow-up data from the interferon α kinoid phase I/II study.
Sex, Age, Specimen part, Disease, Disease stage, Treatment, Subject, Time
View SamplesRheumatoid arthritis (RA) is an inflammatory joint disorder that results in progressive joint damage when insufficiently treated. In order to prevent joint destruction and functional disability in RA, early diagnosis and initiation of appropriate treatment with Disease-Modifying Antirheumatic Drugs (DMARDs) is needed. However, in daily clinical practice, patients may initially display symptoms of arthritis that do not fulfil the classification criteria for a definite diagnosis of RA, or any other joint disease, a situation called Undifferentiated Arthritis (UA). Out of the patients with UA, 30 to 50% usually develop RA, and early identification of these remains a challenge.
Identification of distinct gene expression profiles in the synovium of patients with systemic lupus erythematosus.
Sex, Age, Specimen part, Disease, Treatment
View SamplesObjective: Rituximab displays therapeutic benefits in the treatment of rheumatoid arthritis (RA) patients resistant to TNF blockade. However, the precise role of B cells in the pathogenesis of RA is still unknown. In this study we investigated the global molecular effects of rituximab in synovial biopsies obtained from anti-TNF resistant RA patients before and after administration of the drug.
Rituximab treatment induces the expression of genes involved in healing processes in the rheumatoid arthritis synovium.
Sex, Specimen part, Disease, Disease stage, Treatment
View SamplesIn the lateral root repression system described by Bab et al. (2012), the first asymetric divisions of pericycle cells preceding lateral root formation are repressed during water deficit treatments. During an 8-hr long treatment, an 8-mm long root segment is formed where LR formation has been repressed.
No associated publication
Specimen part, Treatment
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