Gene expression in systemic lupus erythematosus: Bone marrow analysis differentiates active from inactive disease and reveals apoptosis and granulopoiesis signatures

Νάκου, Μαγδαληνή; Knowlton, Nicholas; Frank, Mark Barton; Βertsias, George; Osban, Jeanette; Sandel, C; Papadaki, Helen Α.; Ραπτοπούλου, Αμαλία; Sidiropoulos, Prodromos; Kritikos, Iraklis; Tassiulas, Ioannis; Centola, Michael; Boumpas, Dimitrios T.

doi:10.1002/art.23961

Cited by 69 publications

(66 citation statements)

References 54 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Chemokines: Among the genes that were over-expressed in the peripheral blood relative to the bone marrow of SLE patients, Nakou et al [60] identified a number of chemokines, including CCR5, CXCL3L1, CXCL2 and CXCL3 and other interferon-responsive genes including IL6R. Similarly, Fu et al [61] and Bauer et al [62] also identified chemokines and cytokines whose gene expression was different in SLE than in healthy controls.…”

Section: Other Markersmentioning

confidence: 99%

Customising an antibody leukocyte capture microarray for systemic lupus erythematosus: Beyond biomarker discovery

Lin

Adelstein

et al. 2010

Proteomics Clinical Apps

View full text Add to dashboard Cite

Systemic lupus erythematosus (SLE) is a complex autoimmune disease that has heterogeneous clinical manifestation with diverse patterns of organ involvement, autoantibody profiles and varying degrees of severity of disease. Research and clinical experience indicate that different subtypes of SLE patients will likely benefit from more tailored treatment regimes, but we currently lack a fast and objective test with high enough sensitivity to enable us to perform such sub‐grouping for clinical use. In this article, we review how proteomic technologies could be used as such an objective test. In particular, we extensively review many leukocyte surface markers that are known to have an association with the pathogenesis of SLE, and we discuss how these markers can be used in the further development of a novel SLE‐specific antibody leukocyte capture microarray. In addition, we review some bioinformatics challenges and current methods for using the data generated by these cell‐capture microarrays in clinical use. In a broader context, we hope our experience in developing a disease specific cell‐capture microarray for clinical application can be a guide to other proteomic practitioners who intend to extend their technologies to develop clinical diagnostic and prognostic tests for complex diseases.

show abstract

Section: Other Markersmentioning

confidence: 99%

Customising an antibody leukocyte capture microarray for systemic lupus erythematosus: Beyond biomarker discovery

Lin

Adelstein

et al. 2010

Proteomics Clinical Apps

View full text Add to dashboard Cite

show abstract

“…In bone marrow mononuclear cells (BMMCs) of SLE patients, CCR5 and CX3CR1 expressions were downregulated as compared to those of healthy individuals. However, expressions of CCR5, CXCL3L1, CXCL2 and CXCL3 were upregulated in peripheral blood mononuclear cells (PBMCs) as compared to BMMCs in SLE patients [31]. These genes are associated with chemotaxis properties and migration of leukocytes.…”

Section: Other Cytokine and Chemokine Signatures In Slementioning

confidence: 99%

“…Rus et al [30] identified genes upregulated in active SLE included TNF family molecules (TNF-a converting enzyme; TACE and TNF RII); protease family (TIMP-3 and TIMP-4); neurotrophic factors family (NT-4 and NT-3); IL-17 and IL-13Ra2; and the co-stimulatory molecules (CD40 and CD27), while P-and R-cadherin genes from the adhesion molecule family were downregulated in PBMCs of active patients. Bone marrow cells of active SLE patients displayed apoptotic and granulopoiesis gene signatures [31]. SandrinGarcia et al [34] demonstrated uniquely expressed genes in active SLE patients and in SLE with remission.…”

Section: Other Cytokine and Chemokine Signatures In Slementioning

confidence: 99%

Microarray to deep sequencing: transcriptome and miRNA profiling to elucidate molecular pathways in systemic lupus erythematosus

Rai

Saeidian

et al. 2015

Immunol Res

View full text Add to dashboard Cite

Systemic lupus erythematosus (SLE) is an autoimmune disease with diverse clinical manifestations and autoantibody repertoires. The etiology of SLE is multifactorial involving genetic, epigenetic and environmental factors. This complexity leads to poor prognosis, which poses major challenges in the treatment of SLE. Understanding the complex genetic pathways and regulatory mechanisms operative in SLE was feasible by utilizing several highly efficient molecular biological tools during the past few years. In this perspective, DNA microarray technology offered a high-throughput platform in unraveling SLE-associated genes. Additionally, extensive microarray analysis had demonstrated aberrant DNA methylation pattern and differential microRNAs, thus contributing to the knowledge of epigenetic modulators and posttranscriptional regulatory machinery in SLE. It was through the aid of these technologies that interferon signature was identified as an important contributor in SLE pathogenesis along with dysregulation of cytokine-, chemokine- and apoptosis-related genes. The emergence of next-generation sequencing technologies such as RNA sequencing has added new dimensions in understanding the dynamics of the disease processes. Compared with microarrays, deep sequencing has provided higher resolution in gene expression measurement along with identification of different splicing events, noncoding RNAs and novel loci in SLE. The focus, therefore, has now been shifted toward the identification of novel gene loci and their isoforms, and their implication in disease pathogenesis. This advancement in the technology from microarray to deep sequencing has helped in deciphering the molecular pathways involved in pathogenesis of SLE and opens new avenues to develop novel treatment strategies for SLE.

show abstract

“…Despite chronic neutropenia and hyper-susceptibility to bacterial infections [15][16][17], a significant proportion of SLE patients display elevated levels of immature neutrophils and a pronounced granulopoiesis gene expression signature in cells from both peripheral blood and bone marrow exudates [2,18,19]. In addition, neutrophils are known to infiltrate target organs such as the skin, kidney or vasculature in SLE patients [20][21][22], although the pathogenic nature of such infiltration remains unknown.…”

Section: Pro-inflammatory Neutrophils In Accumulate In Sle Patients Amentioning

confidence: 99%

Pro- and Anti-inflammatory Neutrophils in Lupus

Der¹,

Trigunaite²,

Khan³

et al. 2014

J Clin Cell Immunol

View full text Add to dashboard Cite

A hallmark of SLE is the presence of elevated levels of circulating anti-nuclear autoantibodies specific towards chromatin, histones or dsDNA. Understanding the regulation of antibody production is therefore of utmost importance in understanding lupus pathogenesis. Spearheaded by the identification of accumulating immunosuppressive neutrophils in cancer patients, the nature and function of neutrophils have expanded from a uniform pro-inflammatory cell population to a heterogeneous population of cells with pro-inflammatory or immunosuppressive capacities. While much is known about pro-inflammatory neutrophils and the likely pathogenic function of such cells in lupus, a potential role for immunosuppressive neutrophils in protecting genetically predisposed individuals has only recently emerged. For example, SLE-derived neutrophils spontaneously produce type I interferons (IFNα), strongly associated with disease development, release chromatin-containing neutrophil extracellular traps (NETs), potentially functioning as a source of nuclear auto-antigen, and may activate B cells in a T cell independent fashion. In contrast, levels and functions of regulatory neutrophils (Nregs) involved in T celldependent B cell differentiation and germinal center reactions, are dysregulated in female lupus-prone mice during disease development. Here we review data supporting a role for both pro-and anti-inflammatory neutrophils in lupus.

show abstract

Gene expression in systemic lupus erythematosus: Bone marrow analysis differentiates active from inactive disease and reveals apoptosis and granulopoiesis signatures

Cited by 69 publications

References 54 publications

Customising an antibody leukocyte capture microarray for systemic lupus erythematosus: Beyond biomarker discovery

Customising an antibody leukocyte capture microarray for systemic lupus erythematosus: Beyond biomarker discovery

Microarray to deep sequencing: transcriptome and miRNA profiling to elucidate molecular pathways in systemic lupus erythematosus

Pro- and Anti-inflammatory Neutrophils in Lupus

Contact Info

Product

Resources

About