Coordinate overexpression of interferon‐α–induced genes in systemic lupus erythematosus

Objective To study the contribution of interferon-α (IFNα) and IFNγ to the IFN gene expression signature that has been observed in microarray screens of peripheral blood mononuclear cells (PBMCs) from patients with systemic lupus erythematosus (SLE). Methods Quantitative real-time polymerase chain reaction analysis of healthy control PBMCs was used to determine the relative induction of a panel of IFN-inducible genes (IFIGs) by IFNα and IFNγ. PBMCs from 77 SLE patients were compared with those from 22 disease controls and 28 healthy donors for expression of IFIGs. Results Expression of IFNα-inducible genes was significantly higher in SLE PBMCs than in those from disease controls or healthy donors. The level of expression of all IFIGs in PBMCs from SLE patients with IFNα pathway activation correlated highly with the inherent responsiveness of those genes to IFNα, suggesting coordinate activation of that cytokine pathway. Expression of genes preferentially induced by IFNγ was not significantly increased in SLE PBMCs compared with control PBMCs. IFNα-regulated gene-inducing activity was detected in some SLE plasma samples. Conclusion The coordinate activation of IFNα-induced genes is a characteristic of PBMCs from many SLE patients, supporting the hypothesis that IFNα is the predominant stimulus for IFIG expression in lupus.

[1]  M. Crow,et al.  Measurement of cytokines in autoimmune disease. , 2004, Methods in molecular medicine.

[2]  M. Crow,et al.  Microarray Analysis of Interferon-regulated Genes in SLE , 2003, Autoimmunity.

[3]  B. Kotzin,et al.  Links Between Type I Interferons and the Genetic Basis of Disease in Mouse Lupus , 2003, Autoimmunity.

[4]  M. Crow,et al.  Microarray analysis of gene expression in lupus , 2003, Arthritis research & therapy.

[5]  C. Bao,et al.  Protein interaction for an interferon-inducible systemic lupus associated gene, IFIT1. , 2003, Rheumatology.

[6]  M. Crow.  Interferon-α: A new target for therapy in systemic lupus erythematosus? , 2003 .

[7]  A. Rosen,et al.  Apoptosis in systemic lupus erythematosus , 2003, Current opinion in rheumatology.

[8]  Virginia Pascual,et al.  Plasmacytoid dendritic cells induce plasma cell differentiation through type I interferon and interleukin 6. , 2003, Immunity.

[9]  Michael Zuker,et al.  Mfold web server for nucleic acid folding and hybridization prediction , 2003, Nucleic Acids Res..

[10]  F. Lai,et al.  Inflammatory cytokine gene expression in the urinary sediment of patients with lupus nephritis. , 2003, Arthritis and rheumatism.

[11]  T. Stewart.  Neutralizing interferon alpha as a therapeutic approach to autoimmune diseases. , 2003, Cytokine & growth factor reviews.

[12]  C. Bao,et al.  Analysis of gene expression profiles in human systemic lupus erythematosus using oligonucleotide microarray , 2003, Genes and Immunity.

[13]  Virginia Pascual,et al.  Interferon and Granulopoiesis Signatures in Systemic Lupus Erythematosus Blood , 2003, The Journal of experimental medicine.

[14]  D. Choubey,et al.  Type-I Interferon Receptor Deficiency Reduces Lupus-like Disease in NZB Mice , 2003, The Journal of experimental medicine.

[15]  G. Karypis,et al.  Interferon-inducible gene expression signature in peripheral blood cells of patients with severe lupus , 2003, Proceedings of the National Academy of Sciences of the United States of America.

[16]  J. Demengeot,et al.  Type I Interferon controls the onset and severity of autoimmune manifestations in lpr mice. , 2003, Journal of autoimmunity.

[17]  Fritz Aberger,et al.  Cell-type and Donor-specific Transcriptional Responses to Interferon-α , 2002, The Journal of Biological Chemistry.

[18]  R. Salomon,et al.  Critical Role for STAT4 Activation by Type 1 Interferons in the Interferon-γ Response to Viral Infection , 2002, Science.

[19]  Ion Gresser,et al.  Type I interferons produced by dendritic cells promote their phenotypic and functional activation. , 2002, Blood.

[20]  D. Gladman,et al.  Systemic lupus erythematosus disease activity index 2000. , 2002, The Journal of rheumatology.

[21]  Michel C. Nussenzweig,et al.  Avoiding horror autotoxicus: The importance of dendritic cells in peripheral T cell tolerance , 2002, Proceedings of the National Academy of Sciences of the United States of America.

[22]  R. Steinman.  Inaugural Article : avoiding horror autotoxicus. The importance of dendritic cells in peripheral T cell tolerance , 2002 .

[23]  L. Rönnblom,et al.  A Pivotal Role for the Natural Interferon α–producing Cells (Plasmacytoid Dendritic Cells) in the Pathogenesis of Lupus , 2001, The Journal of experimental medicine.

[24]  B. Croker,et al.  Interferon- (cid:1) is required for lupus nephritis in mice treated with the hydrocarbon oil pristane , 2010 .

[25]  Virginia Pascual,et al.  Induction of Dendritic Cell Differentiation by IFN-α in Systemic Lupus Erythematosus , 2001, Science.

[26]  G. Peltz,et al.  Evidence for an interferon-inducible gene, Ifi202, in the susceptibility to systemic lupus. , 2001, Immunity.

[27]  M. Pfaffl,et al.  A new mathematical model for relative quantification in real-time RT-PCR. , 2001, Nucleic acids research.

[28]  F. Belardelli,et al.  Type i interferons potently enhance humoral immunity and can promote isotype switching by stimulating dendritic cells in vivo. , 2001, Immunity.

[29]  R. Vakkalanka,et al.  Induction of Fas ligand-mediated apoptosis by interferon-alpha. , 2000, Clinical immunology.

[30]  F. Nicoletti,et al.  Dichotomic effects of IFN‐γ on the development of systemic lupus erythematosus‐like syndrome in MRL‐lpr / lpr mice , 2000, European journal of immunology.

[31]  D. Kono,et al.  Treatment of murine lupus with cDNA encoding IFN-γR/Fc , 2000 .

[32]  P. Marrack,et al.  Type I Interferons Keep Activated T Cells Alive , 1999, The Journal of experimental medicine.

[33]  B. Williams,et al.  Identification of genes differentially regulated by interferon α, β, or γ using oligonucleotide arrays , 1998 .

[34]  A. Schwarting,et al.  IFN-gamma receptor signaling is essential for the initiation, acceleration, and destruction of autoimmune kidney disease in MRL-Fas(lpr) mice. , 1998, Journal of immunology.

[35]  B. Ryffel,et al.  IFN-γ Receptor Deletion Prevents Autoantibody Production and Glomerulonephritis in Lupus-Prone (NZB × NZW)F1 Mice , 1998, The Journal of Immunology.

[36]  B. Ryffel,et al.  IFN-gamma receptor deletion prevents autoantibody production and glomerulonephritis in lupus-prone (NZB x NZW)F1 mice. , 1998, Journal of immunology.

[37]  D. Balomenos,et al.  Interferon-gamma is required for lupus-like disease and lymphoaccumulation in MRL-lpr mice. , 1998, The Journal of clinical investigation.

[38]  M. Dalakas,et al.  A Study of the Interferon Antiviral Mechanism: Apoptosis Activation by the 2–5A System , 1997, The Journal of experimental medicine.

[39]  B. Ryffel,et al.  IFN-gamma is essential for the development of autoimmune glomerulonephritis in MRL/Ipr mice. , 1997, Journal of immunology.

[40]  J. Moslehi,et al.  Roles of interferon-gamma and interleukin-4 in murine lupus. , 1997, The Journal of clinical investigation.

[41]  S. Der,et al.  A double-stranded RNA-activated protein kinase-dependent pathway mediating stress-induced apoptosis. , 1997, Proceedings of the National Academy of Sciences of the United States of America.

[42]  Kirk M. Ririe,et al.  Product differentiation by analysis of DNA melting curves during the polymerase chain reaction. , 1997, Analytical biochemistry.

[43]  F. Belardelli,et al.  The neglected role of type I interferon in the T-cell response: implications for its clinical use. , 1996, Immunology today.

[44]  B. Ryffel,et al.  Experimental therapy of systemic lupus erythematosus: the treatment of NZB/W mice with mouse soluble interferon‐γ receptor inhibits the onset of glomerulonephritis , 1995, European journal of immunology.

[45]  S. Goshima,et al.  Up-regulated MHC-class II expression and γ-IFN and soluble IL-2R in lupus nephritis , 1992 .

[46]  L. Rönnblom,et al.  Possible induction of systemic lupus erythematosus by interferon‐α treatment in a patient with a malignant carcinoid tumour , 1990, Journal of internal medicine.

[47]  F. Arnett.  Revised criteria for the classification of rheumatoid arthritis. , 1990, Orthopedic nursing.

[48]  M. Liang,et al.  The American Rheumatism Association 1987 revised criteria for the classification of rheumatoid arthritis. , 1988, Arthritis and rheumatism.

[49]  G. Tsokos,et al.  Deficient ?-interferon production in patients with systemic lupus erythematosus , 1986 .

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

[51]  R. Friedman,et al.  Systemic lupus erythematosus: presence in human serum of an unusual acid-labile leukocyte interferon. , 1982, Science.

[52]  A. Notkins,et al.  Immune interferon in the circulation of patients with autoimmune disease. , 1979, The New England journal of medicine.