Interferon and Granulopoiesis Signatures in Systemic Lupus Erythematosus Blood

By Lynda Bennett, A. Palucka, Edsel Arce, Victoria Cantrell, J. Borvák, Jacques Banchereau, Virginia Pascual. Journal of Experimental Medicine, 2003

2,023 citations recorded by the source corpus.

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.

Subfields: Immunology, Immunology and Allergy

View Paper: https://www.semanticscholar.org/paper/06f3873617af64f468986c1feedad295a4da1566

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Citations in the corpus

Neutrophils Activate Plasmacytoid Dendritic Cells by Releasing Self-DNA–Peptide Complexes in Systemic Lupus Erythematosus (2011, background): “LL37, produced by neutrophils, is highly expressed in the blood of SLE patients (16), raising the possibility that this peptide is involved in the immunogenicity of self-nucleic acids in immune complexes.”
Type I interferon: friend or foe? (2010, background): “A prominent feature of systemic lupus erythematosus (SLE) is the increased expression of type I IFN–regulated genes in blood cells, which is often associated with the presence of IFN in the plasma (Bennett et al., 2003; Rönnblom and Alm, 2003).”
Neutrophils in the activation and regulation of innate and adaptive immunity (2011, background): “In systemic lupus erythematosus (SLE) — a multiorgan autoimmune disease characterized by an IFN and granulopoiesis signature, as well as abnormal B and T cell functio”
Plasmacytoid dendritic cells in immunity (2004, background): “The expression of type 1 interferon genes and interferon-induced genes represent the most salient molecular 'signatures' of SLE peripheral blood cell”
Changes in the pattern of DNA methylation associate with twin discordance in systemic lupus erythematosus. (2010, background): “At any rate, WBCs are commonly used in the search for novel SLE targets and have provided specific signatures associated with SLE pathogenesis (Bennett et al. 2003; Chaussabel et al. 2008).”
Type I interferon in systemic lupus erythematosus and other autoimmune diseases. (2006, background): “Furthermore, treating SLE patients with high-dose intravenous steroids, which induce clinical remission, abrogates the IFN-ab signature in PBMCs (Bennett et al., 2003).”
Personalized Immunomonitoring Uncovers Molecular Networks That Stratify Lupus Patients (2016, positive): “SLE patients display unique blood transcriptional signatures linked to type I interferon (IFN) and granulocytes (Baechler et al., 2003; Bennett et al., 2003; Chaussabel et al., 2008; Chiche et al., 2014).”
The role of defective clearance of apoptotic cells in systemic autoimmunity (2010, background): “Type I IFNs Type I IFNs activate DCs, B cells, T cells and natural killer cells and have emerged as critical molecules in SLE patients, in whom gene-expression studies in leukocytes reveal evidence of in vivo exposure to these cytokines”
Netting Neutrophils Are Major Inducers of Type I IFN Production in Pediatric Systemic Lupus Erythematosus (2011, background): “Genomic approaches have shown that >95% of children and 50 to 70% of adults with SLE display a type I IFN signature as measured by peripheral blood mononuclear cell (PBMC) gene expression profiling (9, 10).”