Interferon and granulopoiesis signatures in systemic lupus erythematosus blood.
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.
Bennett
Lynda
L
Baylor Institute for Immunology Research, Dallas, TX 75204, USA.
Palucka
A Karolina
AK
Arce
Edsel
E
Cantrell
Victoria
V
Borvak
Josef
J
Banchereau
Jacques
J
Pascual
Virginia
V
D002648:Child; D005260:Female; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D006098:Granulocytes / Q000166:cytology / Q000276:immunology / Q000502:physiology*; D006801:Humans; D016898:Interferon-alpha / Q000276:immunology / Q000378:metabolism*; D019891:Leukopoiesis; D008180:Lupus Erythematosus, Systemic / Q000097:blood* / Q000235:genetics* / Q000276:immunology; D008297:Male; D020411:Oligonucleotide Array Sequence Analysis; D013223:Statistics as Topic
D016898:Interferon-alpha