Human Gene Set: BENNETT_SYSTEMIC_LUPUS_ERYTHEMATOSUS


Standard name BENNETT_SYSTEMIC_LUPUS_ERYTHEMATOSUS
Systematic name M12175
Brief description Genes significantly up-regulated in the blood mononuclear cells from patients with systemic lupus erythematosus compared to those from healthy persons.
Full description or abstract Systemic lupus erythematosus (SLE) is a prototype systemic autoimmune disease characterized by flares of high morbidity. Using oligonucleotide microarrays, we now show that active SLE can be distinguished by a remarkably homogeneous gene expression pattern with overexpression of granulopoiesis-related and interferon (IFN)-induced genes. Using the most stringent statistical analysis (Bonferroni correction), 15 genes were found highly up-regulated in SLE patients, 14 of which are targets of IFN and one, defensin DEFA-3, a major product of immature granulocytes. A more liberal correction (Benjamini and Hochberg correction) yielded 18 additional genes, 12 of which are IFN-regulated and 4 granulocyte-specific. Indeed immature neutrophils were identified in a large fraction of SLE patients white blood cells. High dose glucocorticoids, a standard treatment of disease flares, shuts down the interferon signature, further supporting the role of this cytokine in SLE. The expression of 10 genes correlated with disease activity according to the SLEDAI. The most striking correlation (P < 0.001, r = 0.55) was found with the formyl peptide receptor-like 1 protein that mediates chemotactic activities of defensins. Therefore, while the IFN signature confirms the central role of this cytokine in SLE, microarray analysis of blood cells reveals that immature granulocytes may be involved in SLE pathogenesis.
Collection C2: Curated
      CGP: Chemical and Genetic Perturbations
Source publication Pubmed 12642603   Authors: Bennett L,Palucka AK,Arce E,Cantrell V,Borvak J,Banchereau J,Pascual V
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Source species Homo sapiens
Contributed by Kevin Vogelsang (MSigDB Team)
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identifier namespace		 HUMAN_SEQ_ACCESSION
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Version history 3.0: Renamed from BENNETT_SLE_UP

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