Deconvolution of blood microarray data identifies cellular activation patterns in systemic lupus erythematosus.
Deconvolution of blood microarray data identifies cellular activation patterns in systemic lupus erythematosus.
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DOI：
10.1371/journal.pone.0006098
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发表时间：
2009-07-01
期刊：
影响因子：
3.7
通讯作者：
Clark HF
中科院分区：
文献类型：
--
作者：
Abbas AR;Wolslegel K;Seshasayee D;Modrusan Z;Clark HF
系统性红斑狼疮（SLE）是一种全身性自身免疫性疾病，具有复杂的细胞和分子特征谱，包括外周血白细胞群体的几个显著变化。这些变化包括全身性白细胞减少、B和T细胞活化以及粒细胞成熟。SLE在外周血中的表现是疾病的核心，但尚未完全了解。一种用于严格表征混合细胞群变化的技术，微阵列表达去卷积，已应用于生物学的几个领域，但不适用于SLE或血液。在这里，我们证明了微阵列表达去卷积准确地量化了真实的血液样品和免疫衍生细胞系的混合物的成分。我们的特点是广泛的外周血白细胞类型和状态的SLE发现新的模式，包括：NK和T辅助淋巴细胞的特异性激活，这些模式之间的关系，以及与临床变量和措施的相关性。SLE患者单核细胞、NK细胞和辅助性T细胞的扩增和活化至少部分地是这种疾病的显著干扰素特征的基础。本文揭示的这些和其他白细胞动力学模式与疾病的严重程度和治疗相关，提示了潜在的新治疗方法，并扩展了我们对狼疮病理学作为一种涉及免疫系统多个分支的复杂自身免疫性疾病的理解。
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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影响因子：
--
作者：
Green, Matthew R. J.;Kennell, Amy S. M.;Salaman, Myer R.
通讯作者：
Salaman, Myer R.
DOI：
10.1084/jem.20021553
发表时间：
2003-03-17
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Bennett L;Palucka AK;Arce E;Cantrell V;Borvak J;Banchereau J;Pascual V
通讯作者：
Pascual V
影响因子：
56.9
作者：
Blanco, P;Palucka, AK;Banchereau, J
通讯作者：
Banchereau, J
影响因子：
13.5
作者：
Helbig, KJ;Lau, DTY;Beard, MR
通讯作者：
Beard, MR
影响因子：
--
作者：
Papadimitraki, Eva D.;Choulaki, Christianna;Boumpas, Dimitrios T.
通讯作者：
Boumpas, Dimitrios T.