Expression of cytokine- and chemokine-related genes in peripheral blood mononuclear cells from lupus patients by cDNA array.

Systemic lupus erythematosus (SLE) is characterized by diverse and complex immune abnormalities. In an effort to begin to characterize the full complexity of immune abnormalities, the expression pattern of 375 potentially relevant genes was analyzed using peripheral blood mononuclear cells (PBMC) from 21 SLE patients and 12 controls by cDNA arrays. When mean gene expression for patients was compared to controls, 50 genes were identified that exhibited more than 2.5-fold difference in expression level. By the Mann-Whitney U test, 20 genes were significantly different (P < 0.05) between patients and controls. Most of these genes have not been previously associated with SLE and belong to a variety of families such as TNF/death receptor, IL-1 cytokine family, and IL-8 and its receptors. Hierarchical clustering of samples and differentially expressed genes revealed that with few exceptions, patients clustered separately from controls. These results highlight the potential use of the microarray data in identifying genes associated with SLE, which could become candidate molecular markers or future therapeutic targets.

[1]  J. Gray,et al.  Decreased production of TGF-beta by lymphocytes from patients with systemic lupus erythematosus. , 1998, Journal of immunology.

[2]  P. Surányi,et al.  Correlations of Monocyte Phagocytic Receptor Expressions with Serum Immune Complex Level in Systemic Lupus Erythematosus , 1994, Scandinavian journal of immunology.

[3]  J F Fries,et al.  The 1982 revised criteria for the classification of systemic lupus erythematosus. , 1982, Arthritis and rheumatism.

[4]  Katsuaki Sato,et al.  Chemokine Receptor Expressions and Responsiveness of Cord Blood T Cells , 2001, The Journal of Immunology.

[5]  Ash A. Alizadeh,et al.  Distinct types of diffuse large B-cell lymphoma identified by gene expression profiling , 2000, Nature.

[6]  A. Custovic,et al.  Apoptosis signals in atopy and asthma measured with cDNA arrays , 2001, Clinical and experimental immunology.

[7]  Christian A. Rees,et al.  Molecular portraits of human breast tumours , 2000, Nature.

[8]  J. Trent,et al.  Analysis of gene expression in multiple sclerosis lesions using cDNA microarrays , 1999 .

[9]  M. Weller,et al.  Expression of TRAIL receptors in human autoreactive and foreign antigen-specific T cells , 2000, Cell Death and Differentiation.

[10]  A. Zernecke,et al.  Combinatorial Model of Chemokine Involvement in Glomerular Monocyte Recruitment: Role of CXC Chemokine Receptor 2 in Infiltration During Nephrotoxic Nephritis1 , 2001, The Journal of Immunology.

[11]  M. Liang,et al.  Measurement of systemic lupus erythematosus activity in clinical research. , 1988, Arthritis and rheumatism.

[12]  R. W. Davis,et al.  Discovery and analysis of inflammatory disease-related genes using cDNA microarrays. , 1997, Proceedings of the National Academy of Sciences of the United States of America.

[13]  H. Spring,et al.  Urokinase‐type plasminogen activator enhances invasion of human T cells (Jurkat) into a fibrin matrix , 1994, Journal of leukocyte biology.

[14]  K. Miura,et al.  Quantitative assessment of DNA microarrays--comparison with Northern blot analyses. , 2001, Genomics.

[15]  Ronald W. Davis,et al.  Functional characterization of the S. cerevisiae genome by gene deletion and parallel analysis. , 1999, Science.

[16]  F. Luscinskas,et al.  MCP-1 and IL-8 trigger firm adhesion of monocytes to vascular endothelium under flow conditions , 1999, Nature.

[17]  R. Tibshirani,et al.  Significance analysis of microarrays applied to the ionizing radiation response , 2001, Proceedings of the National Academy of Sciences of the United States of America.

[18]  D. Botstein,et al.  Cluster analysis and display of genome-wide expression patterns. , 1998, Proceedings of the National Academy of Sciences of the United States of America.

[19]  S. Gygi,et al.  Correlation between Protein and mRNA Abundance in Yeast , 1999, Molecular and Cellular Biology.

[20]  T. Vischer,et al.  Circulating levels of tumor necrosis factor soluble receptors in systemic lupus erythematosus are significantly higher than in other rheumatic diseases and correlate with disease activity. , 1997, The Journal of rheumatology.

[21]  Low levels of interleukin-1 receptor antagonist coincide with kidney involvement in systemic lupus erythematosus. , 1997, British journal of rheumatology.

[22]  Eric J. Kunkel,et al.  CCR7 Expression and Memory T Cell Diversity in Humans1 , 2001, The Journal of Immunology.

[23]  U. Alon,et al.  Broad patterns of gene expression revealed by clustering analysis of tumor and normal colon tissues probed by oligonucleotide arrays. , 1999, Proceedings of the National Academy of Sciences of the United States of America.

[24]  YOUHAI H. Chen,et al.  Tumor Necrosis Factor–Related Apoptosis-Inducing Ligand (Trail) Is an Inhibitor of Autoimmune Inflammation and Cell Cycle Progression , 2000, The Journal of experimental medicine.

[25]  B. Hilliard,et al.  Roles of TNF-Related Apoptosis-Inducing Ligand in Experimental Autoimmune Encephalomyelitis1 , 2001, The Journal of Immunology.

[26]  M. Arima,et al.  Expression of interleukin-16 by human epithelial cells. Inhibition by dexamethasone. , 1999, American journal of respiratory cell and molecular biology.

[27]  D. Lockhart,et al.  Analysis of gene expression profiles in normal and neoplastic ovarian tissue samples identifies candidate molecular markers of epithelial ovarian cancer. , 2001, Proceedings of the National Academy of Sciences of the United States of America.

[28]  P. Krammer,et al.  Surface expression of TRAIL/Apo‐2 ligand in activated mouse T and B cells , 1998, European journal of immunology.

[29]  C. Marsh,et al.  The combination of endotoxin and dexamethasone induces type II interleukin 1 receptor (IL-1r II) in monocytes: a comparison to interleukin 1 beta (IL-1 beta) and interleukin 1 receptor antagonist (IL-1ra). , 1996, Cytokine.

[30]  B. Groner,et al.  Cooperation Among Stat1, Glucocorticoid Receptor, and PU.1 in Transcriptional Activation of the High-Affinity Fcγ Receptor I in Monocytes1 , 2000, The Journal of Immunology.

[31]  P. Allavena,et al.  Induction of Functional IL-8 Receptors by IL-4 and IL-13 in Human Monocytes1 , 2000, The Journal of Immunology.

[32]  K. Resch,et al.  Effects of IL‐1 receptor accessory protein on IL‐1 binding , 1998, FEBS Letters.

[33]  M. Goto,et al.  Production of intracellular and extracellular interleukin-1 alpha and interleukin-1 beta by peripheral blood monocytes from patients with connective tissue diseases. , 1991, Annals of the rheumatic diseases.

[34]  Kenichi Watanabe,et al.  Spontaneous production of bone-resorbing lymphokines by B cells in patients with systemic lupus erythematosus , 1989, Journal of Clinical Immunology.

[35]  H. Euler,et al.  Recombinant human granulocyte colony stimulating factor in patients with systemic lupus erythematosus associated neutropenia and refractory infections. , 1997, The Journal of rheumatology.

[36]  S. Zucker,et al.  Increased serum stromelysin-1 levels in systemic lupus erythematosus: lack of correlation with disease activity. , 1999, The Journal of rheumatology.

[37]  N. Young,et al.  Pharmacologic doses of granulocyte colony-stimulating factor affect cytokine production by lymphocytes in vitro and in vivo. , 2000, Blood.

[38]  I. Herr,et al.  TRAIL/Apo‐2‐ligand‐induced apoptosis in human T cells , 1998, European journal of immunology.

[39]  S. Nisole,et al.  Inhibition of HIV infection by the cytokine midkine. , 2001, Virology.

[40]  D. Sackett,et al.  Derivation of the SLEDAI. A disease activity index for lupus patients. The Committee on Prognosis Studies in SLE. , 1992, Arthritis and rheumatism.

[41]  A. Tsirogianni,et al.  Serum IL-6, TNFα, p55 srTNFα, p75 srTNFα, srIL-2α Levels and Disease Acitivity in Systemic Lupus Erythematosus , 1999, Clinical Rheumatology.

[42]  S. Durham,et al.  Expression of IL-16 in allergen-induced late-phase nasal responses and relation to topical glucocorticosteroid treatment. , 1997, The Journal of allergy and clinical immunology.