Deconvolution of Blood Microarray Data Identifies Cellular Activation Patterns in Systemic Lupus Erythematosus

被引:305
作者
Abbas, Alexander R.
Wolslegel, Kristen
Seshasayee, Dhaya
Modrusan, Zora
Clark, Hilary F.
机构
[1] Department of Bioinformatics, Genentech, Inc., South San Francisco, CA
[2] Department of Immunology, Genentech, Inc., South San Francisco, CA
[3] Department of Molecular Biology, Genentech, Inc., South San Francisco, CA
来源
PLOS ONE | 2009年 / 4卷 / 07期
关键词
GENE-EXPRESSION; T-CELLS; TRANSCRIPTION FACTORS; DISEASE-ACTIVITY; I INTERFERON; IFN-ALPHA; INDUCTION; FAMILIES; VITRO; RISK;
D O I
10.1371/journal.pone.0006098
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
Systemic Lupus Erythematosus (SLE) is a systemic autoimmune disease with a complex spectrum of cellular and molecular characteristics including several dramatic changes in the populations of peripheral leukocytes. These changes include general leukopenia, activation of B and T cells, and maturation of granulocytes. The manifestation of SLE in peripheral blood is central to the disease but is incompletely understood. A technique for rigorously characterizing changes in mixed populations of cells, microarray expression deconvolution, has been applied to several areas of biology but not to SLE or to blood. Here we demonstrate that microarray expression deconvolution accurately quantifies the constituents of real blood samples and mixtures of immune-derived cell lines. We characterize a broad spectrum of peripheral leukocyte cell types and states in SLE to uncover novel patterns including: specific activation of NK and T helper lymphocytes, relationships of these patterns to each other, and correlations to clinical variables and measures. The expansion and activation of monocytes, NK cells, and T helper cells in SLE at least partly underlie this disease's prominent interferon signature. These and other patterns of leukocyte dynamics uncovered here correlate with disease severity and treatment, suggest potential new treatments, and extend our understanding of lupus pathology as a complex autoimmune disease involving many arms of the immune system.
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