Volume 6 Supplement 3

Global Arthritis Research Network (GARN): 4th World Congress on Arthritis in Montreal

Open Access

Insights into systemic lupus erythematosus pathogenesis through blood global gene expression analysis

  • V Pascual1,
  • L Bennett1,
  • F Allantaz1,
  • E Arce1 and
  • J Banchereau1
Arthritis Res Ther20046(Suppl 3):45

https://doi.org/10.1186/ar1380

Published: 13 September 2004

Systemic lupus erythematosus (SLE) is a prototype systemic autoimmune disease characterized by flares of high morbidity for which we have no predictors. We used oligonucleotide microarrays to analyze the genes expressed by blood mononuclear cells from active SLE patients, arthritis patients and healthy controls. Here we 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 upregulated in SLE patients, 14 of which are either well-known or newly identified targets of IFN. The other gene is the defensin DEFA-3, a major product of immature granulocytes. A more liberal correction to the pairwise tests (Benjamini and Hochberg correction) yielded 16 additional genes, 12 of which are known to be IFN-regulated and four to be granulocyte specific. High-dose intravenous infusion of glucocorticoids, one of the standard treatments of disease flares, shuts down the IFN signature, further supporting the critical role of this cytokine in SLE. Furthermore, we have identified a set of 10 genes whose expression correlated with disease activity according to the SLE Disease Activity Index. 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, the microarray analysis of blood cells reveals that immature granulocytes may be involved in SLE pathogenesis.

Authors’ Affiliations

(1)
Baylor Institute for Immunology Research

Copyright

© BioMed Central Ltd 2004

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