Interferon and granulopoiesis signatures in systemic lupus erythematosus blood

Lynda Bennett, A. Karolina Palucka, Edsel Arce, Victoria Cantrell, Josef Borvak, Jacques Banchereau, Virginia Pascual

Research output: Contribution to journalArticle

1310 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)711-723
Number of pages13
JournalJournal of Experimental Medicine
Volume197
Issue number6
DOIs
StatePublished - Mar 17 2003

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Systemic Lupus Erythematosus
Interferons
Granulocytes
Defensins
Formyl Peptide Receptor
Cytokines
Genes
Gene Expression
Microarray Analysis
Oligonucleotide Array Sequence Analysis
Glucocorticoids
Autoimmune Diseases
Blood Cells
Neutrophils
Leukocytes
Morbidity
Proteins

Keywords

  • Autoimmunity
  • Glucocorticoid
  • Immature granulocytes
  • Leukocytes
  • Microarray

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

Cite this

Bennett, L., Palucka, A. K., Arce, E., Cantrell, V., Borvak, J., Banchereau, J., & Pascual, V. (2003). Interferon and granulopoiesis signatures in systemic lupus erythematosus blood. Journal of Experimental Medicine, 197(6), 711-723. https://doi.org/10.1084/jem.20021553

Interferon and granulopoiesis signatures in systemic lupus erythematosus blood. / Bennett, Lynda; Palucka, A. Karolina; Arce, Edsel; Cantrell, Victoria; Borvak, Josef; Banchereau, Jacques; Pascual, Virginia.

In: Journal of Experimental Medicine, Vol. 197, No. 6, 17.03.2003, p. 711-723.

Research output: Contribution to journalArticle

Bennett, L, Palucka, AK, Arce, E, Cantrell, V, Borvak, J, Banchereau, J & Pascual, V 2003, 'Interferon and granulopoiesis signatures in systemic lupus erythematosus blood', Journal of Experimental Medicine, vol. 197, no. 6, pp. 711-723. https://doi.org/10.1084/jem.20021553
Bennett, Lynda ; Palucka, A. Karolina ; Arce, Edsel ; Cantrell, Victoria ; Borvak, Josef ; Banchereau, Jacques ; Pascual, Virginia. / Interferon and granulopoiesis signatures in systemic lupus erythematosus blood. In: Journal of Experimental Medicine. 2003 ; Vol. 197, No. 6. pp. 711-723.
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