Cytokines and Cytokine Profiles in Human Autoimmune Diseases and Animal Models of Autoimmunity

The precise pathomechanisms of human autoimmune diseases are still poorly understood. However, a deepened understanding of these is urgently needed to improve disease prevention and early detection and guide more specific treatment approaches. In recent years, many new genes and signalling pathways involved in autoimmunity with often overlapping patterns between different disease entities have been detected. Major contributions were made by experiments using DNA microarray technology, which has been used for the analysis of gene expression patterns in chronic inflammatory and autoimmune diseases, among which were rheumatoid arthritis, systemic lupus erythematosus, psoriasis, systemic sclerosis, multiple sclerosis, and type-1 diabetes. In systemic lupus erythematosus, a so-called interferon signature has been identified. In psoriasis, researchers found a particular immune signalling cluster. Moreover the identification of a new subset of inflammatory T cells, so-called Th17 T cells, secreting interleukin (IL)-17 as one of their major cytokines and the identification of the IL-23/IL-17 axis of inflammation regulation, have significantly improved our understanding of autoimmune diseases. Since a plethora of new treatment approaches using antibodies or small molecule inhibitors specifically targeting cytokines, cellular receptors, or signalling mechanisms has emerged in recent years, more individualized treatment for affected patients may be within reach in the future.

[1]  L. Fry,et al.  Triggering psoriasis: the role of infections and medications. , 2007, Clinics in dermatology.

[2]  David H. Miller,et al.  A controlled trial of natalizumab for relapsing multiple sclerosis. , 2003, The New England journal of medicine.

[3]  R. Lempicki,et al.  Evaluation of gene expression measurements from commercial microarray platforms. , 2003, Nucleic acids research.

[4]  J. Manson,et al.  Biomarkers of inflammation and development of rheumatoid arthritis in women from two prospective cohort studies. , 2009, Arthritis and rheumatism.

[5]  W. Robinson,et al.  Proteomic biomarkers for autoimmune disease , 2006, Proteomics.

[6]  Chandra Mohan,et al.  Proteomic toolbox for autoimmunity research. , 2009, Autoimmunity reviews.

[7]  J. Smolen,et al.  Effect of interleukin-6 receptor inhibition with tocilizumab in patients with rheumatoid arthritis (OPTION study): a double-blind, placebo-controlled, randomised trial , 2008, The Lancet.

[8]  P. Brown,et al.  Protein microarrays for highly parallel detection and quantitation of specific proteins and antibodies in complex solutions , 2001, Genome Biology.

[9]  T. Mcclanahan,et al.  IL-27, a heterodimeric cytokine composed of EBI3 and p28 protein, induces proliferation of naive CD4+ T cells. , 2002, Immunity.

[10]  Chandra Mohan,et al.  Elevated Urinary VCAM-1, P-Selectin, Soluble TNF Receptor-1, and CXC Chemokine Ligand 16 in Multiple Murine Lupus Strains and Human Lupus Nephritis1 , 2007, The Journal of Immunology.

[11]  K. Öberg,et al.  Autoimmune Phenomena in Patients with Malignant Carcinoid Tumors During Interferon-α Treatment , 1991 .

[12]  G. Szegedi,et al.  Genome‐scale Assessment of Molecular Pathology in Systemic Autoimmune Diseases using Microarray Technology: A Potential Breakthrough Diagnostic and Individualized Therapy‐design Tool , 2006, Scandinavian journal of immunology.

[13]  Wentian Li,et al.  Elevated Serum Levels of Interferon-Regulated Chemokines Are Biomarkers for Active Human Systemic Lupus Erythematosus , 2006, PLoS medicine.

[14]  Jorge R. Oksenberg,et al.  Gene-microarray analysis of multiple sclerosis lesions yields new targets validated in autoimmune encephalomyelitis , 2002, Nature Medicine.

[15]  Joachim Reischl,et al.  Increased expression of Wnt5a in psoriatic plaques. , 2007, The Journal of investigative dermatology.

[16]  A. Lutterotti,et al.  Genetic variants in the tumor necrosis factor receptor II gene in patients with multiple sclerosis. , 2004, Tissue antigens.

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

[18]  M. Lebwohl,et al.  Efficacy and safety of ustekinumab, a human interleukin-12/23 monoclonal antibody, in patients with psoriasis: 52-week results from a randomised, double-blind, placebo-controlled trial (PHOENIX 2) , 2008, The Lancet.

[19]  F. Ponchel,et al.  Interleukin-7 in rheumatoid arthritis. , 2008, Rheumatology.

[20]  H. Thiesen,et al.  Identification of new quantitative trait loci in mice with collagen-induced arthritis. , 2004, Arthritis and rheumatism.

[21]  E. Tindall,et al.  Treatment of rheumatoid arthritis with a recombinant human tumor necrosis factor receptor (p75)-Fc fusion protein. , 1997, The New England journal of medicine.

[22]  M. Dhodapkar,et al.  Increased Expression of Interleukin 23 p19 and p40 in Lesional Skin of Patients with Psoriasis Vulgaris , 2004, The Journal of experimental medicine.

[23]  H. Berg Cold Spring Harbor Symposia on Quantitative Biology.: Vol. LII. Evolution of Catalytic Functions. Cold Spring Harbor Laboratory, Cold Spring Harbor, NY, 1987, ISBN 0-87969-054-2, xix + 955 pp., US $150.00. , 1989 .

[24]  J. Ortonne Psoriasis, syndrome métabolique et ses composants , 2008 .

[25]  J. Woody,et al.  Randomised double-blind comparison of chimeric monoclonal antibody to tumour necrosis factor α (cA2) versus placebo in rheumatoid arthritis , 1994, The Lancet.

[26]  Xuejun Liu,et al.  Characterization of heterogeneity in the molecular pathogenesis of lupus nephritis from transcriptional profiles of laser-captured glomeruli. , 2004, The Journal of clinical investigation.

[27]  J. Satoh,et al.  Microarray analysis identifies an aberrant expression of apoptosis and DNA damage-regulatory genes in multiple sclerosis , 2005, Neurobiology of Disease.

[28]  T. Kishimoto,et al.  Efficacy and safety of tocilizumab in patients with systemic-onset juvenile idiopathic arthritis: a randomised, double-blind, placebo-controlled, withdrawal phase III trial , 2008, The Lancet.

[29]  P. Mease,et al.  Etanercept in the treatment of psoriatic arthritis and psoriasis: a randomised trial , 2000, The Lancet.

[30]  P. Wernhoff,et al.  Using an advanced intercross line to identify quantitative trait loci controlling immune response during collagen-induced arthritis , 2007, Genes and Immunity.

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

[32]  T. Schnitzer,et al.  Serum interferon levels in patients with systemic lupus erythematosus. , 1982, Arthritis and rheumatism.

[33]  T. Martin,et al.  IL-17 in synovial fluids from patients with rheumatoid arthritis is a potent stimulator of osteoclastogenesis. , 1999, The Journal of clinical investigation.

[34]  Bonnie Bruce,et al.  Antigen microarray profiling of autoantibodies in rheumatoid arthritis. , 2005, Arthritis and rheumatism.

[35]  P. Solenberg,et al.  Identification of blood biomarkers of rheumatoid arthritis by transcript profiling of peripheral blood mononuclear cells from the rat collagen-induced arthritis model , 2006, Arthritis research & therapy.

[36]  B. Nickoloff Cracking the cytokine code in psoriasis , 2007, Nature Medicine.

[37]  J G Krueger,et al.  Molecular classification of psoriasis disease-associated genes through pharmacogenomic expression profiling , 2001, The Pharmacogenomics Journal.

[38]  D. Gladman,et al.  Adalimumab for the treatment of patients with moderately to severely active psoriatic arthritis: results of a double-blind, randomized, placebo-controlled trial. , 2005, Arthritis and rheumatism.

[39]  C. Boitard,et al.  Oral insulin administration and residual (β-cell function in recent-onset type 1 diabetes: a multicentre randomised controlled trial , 2000, The Lancet.

[40]  P. Lipsky,et al.  Infliximab (chimeric anti-tumour necrosis factor α monoclonal antibody) versus placebo in rheumatoid arthritis patients receiving concomitant methotrexate: a randomised phase III trial , 1999, The Lancet.

[41]  J. Harley,et al.  Genetics of human systemic lupus erythematosus: the emerging picture. , 2004, Current opinion in immunology.

[42]  K. Vandenbroeck,et al.  Signalling, inflammation and arthritis: crossed signals: the role of interleukin (IL)-12, -17, -23 and -27 in autoimmunity. , 2008, Rheumatology.

[43]  J. Bos,et al.  In Vitro and In Situ Expression of IL-23 by Keratinocytes in Healthy Skin and Psoriasis Lesions: Enhanced Expression in Psoriatic Skin , 2006, The Journal of Immunology.

[44]  Eshrat S. Emamian,et al.  The use of microarrays to study autoimmunity. , 2004, The journal of investigative dermatology. Symposium proceedings.

[45]  L. Magder,et al.  Expression of cytokine- and chemokine-related genes in peripheral blood mononuclear cells from lupus patients by cDNA array. , 2002, Clinical immunology.

[46]  Thomas Häupl,et al.  Sialic acid-binding Ig-like lectin 1 expression in inflammatory and resident monocytes is a potential biomarker for monitoring disease activity and success of therapy in systemic lupus erythematosus. , 2008, Arthritis and rheumatism.

[47]  K. Kikly,et al.  The IL-23/Th(17) axis: therapeutic targets for autoimmune inflammation. , 2006, Current opinion in immunology.

[48]  A. Cope,et al.  Emerging approaches for the therapy of autoimmune and chronic inflammatory disease. , 2004, Current opinion in immunology.

[49]  J. Fries,et al.  Proteomic analysis of secreted proteins in early rheumatoid arthritis: anti-citrulline autoreactivity is associated with up regulation of proinflammatory cytokines , 2006, Annals of the rheumatic diseases.

[50]  C. Nguyen,et al.  Gene expression profiles in psoriasis: analysis of impact of body site location and clinical severity , 2005, The British journal of dermatology.

[51]  H. Weiner,et al.  Oral tolerance to myelin basic protein and natural recovery from experimental autoimmune encephalomyelitis are associated with downregulation of inflammatory cytokines and differential upregulation of transforming growth factor beta, interleukin 4, and prostaglandin E expression in the brain , 1992, The Journal of experimental medicine.

[52]  M. Genovese,et al.  Interleukin-6 receptor inhibition with tocilizumab reduces disease activity in rheumatoid arthritis with inadequate response to disease-modifying antirheumatic drugs: the tocilizumab in combination with traditional disease-modifying antirheumatic drug therapy study. , 2008, Arthritis and rheumatism.

[53]  David Botstein,et al.  Systemic and cell type-specific gene expression patterns in scleroderma skin , 2003, Proceedings of the National Academy of Sciences of the United States of America.

[54]  A. Bowcock,et al.  Psoriasis pathophysiology: current concepts of pathogenesis , 2005, Annals of the rheumatic diseases.

[55]  L. Staudt,et al.  Expression profiling identifies responder and non-responder phenotypes to interferon-beta in multiple sclerosis. , 2003, Brain : a journal of neurology.

[56]  R. Gold,et al.  Gene expression profiling of the nervous system in murine experimental autoimmune encephalomyelitis. , 2001, Brain : a journal of neurology.

[57]  Xinhua Yu,et al.  Dissecting the genetic basis of rheumatoid arthritis in mouse models. , 2006, Current pharmaceutical design.

[58]  P. Villiger,et al.  Nonsteroidal anti-inflammatory drugs in systemic lupus erythematosus , 2000, Lupus.

[59]  G. Ebers,et al.  Genetic epidemiology: the use of old and new tools for multiple sclerosis , 2008, Trends in Neurosciences.

[60]  A. Gottlieb,et al.  Etanercept and clinical outcomes, fatigue, and depression in psoriasis: double-blind placebo-controlled randomised phase III trial , 2006, The Lancet.

[61]  R. Hirsch,et al.  EXACERBATIONS OF MULTIPLE SCLEROSIS IN PATIENTS TREATED WITH GAMMA INTERFERON , 1987, The Lancet.

[62]  K. Sekizawa,et al.  Early molecular and cellular events of oxidant-induced pulmonary fibrosis in rats. , 2000, Toxicology and applied pharmacology.

[63]  S. Nakae,et al.  Suppression of Immune Induction of Collagen-Induced Arthritis in IL-17-Deficient Mice 1 , 2003, The Journal of Immunology.

[64]  Z. Szallasi,et al.  Reliability and reproducibility issues in DNA microarray measurements. , 2006, Trends in genetics : TIG.

[65]  P. Emery,et al.  Double-blind randomized controlled clinical trial of the interleukin-6 receptor antagonist, tocilizumab, in European patients with rheumatoid arthritis who had an incomplete response to methotrexate. , 2006, Arthritis and rheumatism.

[66]  A. Bowcock The genetics of psoriasis and autoimmunity. , 2005, Annual review of genomics and human genetics (Print).

[67]  S. Tyring,et al.  Ustekinumab for chronic plaque psoriasis , 2008, The Lancet.

[68]  A. Kimball,et al.  Efficacy and safety of ustekinumab, a human interleukin-12/23 monoclonal antibody, in patients with psoriasis: 76-week results from a randomised, double-blind, placebo-controlled trial (PHOENIX 1) , 2008, The Lancet.

[69]  M. Sospedra,et al.  When T cells recognize a pattern, they might cause trouble. , 2006, Current opinion in immunology.

[70]  S. Skurkovich,et al.  Anticytokine therapy--new approach to the treatment of autoimmune and cytokine-disturbance diseases. , 2002, Medical hypotheses.

[71]  M. Carroll,et al.  Innate immunity in the etiopathology of autoimmunity , 2001, Nature Immunology.

[72]  A. Oturai,et al.  Gene expression analysis of interferon-β treatment in multiple sclerosis , 2008, Multiple sclerosis.

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

[74]  T. Tedder,et al.  Quantitative Genetic Variation in CD19 Expression Correlates with Autoimmunity1 , 2000, The Journal of Immunology.

[75]  L. V. D. van de Putte,et al.  A single dose, placebo controlled study of the fully human anti-tumor necrosis factor-alpha antibody adalimumab (D2E7) in patients with rheumatoid arthritis. , 2002, The Journal of rheumatology.

[76]  H. Makino,et al.  Production of interleukin-7 and interleukin-15 by fibroblast-like synoviocytes from patients with rheumatoid arthritis. , 1999, Arthritis and rheumatism.

[77]  Ming-Fei Liu,et al.  Function of interleukin-20 as a proinflammatory molecule in rheumatoid and experimental arthritis. , 2006, Arthritis and rheumatism.

[78]  P. Gregersen,et al.  Peripheral blood gene expression profiling in rheumatoid arthritis , 2005, Genes and Immunity.

[79]  S. Ibrahim,et al.  Gene-expression profile of collagen-induced arthritis. , 2002, Journal of autoimmunity.

[80]  P. Parren,et al.  Targeting interleukin-15 in patients with rheumatoid arthritis: a proof-of-concept study. , 2005, Arthritis and rheumatism.

[81]  Christine H Chung,et al.  Genomics and proteomics: emerging technologies in clinical cancer research. , 2007, Critical reviews in oncology/hematology.

[82]  P. Valdez,et al.  Interleukin-22, a TH17 cytokine, mediates IL-23-induced dermal inflammation and acanthosis , 2007, Nature.

[83]  M. Gadina,et al.  Signalling, inflammation and arthritis: Crossed signals: the role of interleukin-15 and -18 in autoimmunity. , 2008, Rheumatology.

[84]  J. Hillert,et al.  Multiple sclerosis: a modifying influence of HLA class I genes in an HLA class II associated autoimmune disease. , 2000 .

[85]  C. King,et al.  The modulatory capacity of interleukin-21 in the pathogenesis of autoimmune disease. , 2008, Frontiers in bioscience : a journal and virtual library.

[86]  A. Gottlieb Psoriasis: emerging therapeutic strategies , 2005, Nature Reviews Drug Discovery.

[87]  V. Rivera,et al.  Gene expression profiling of relevant biomarkers for treatment evaluation in multiple sclerosis , 2004, Journal of Neuroimmunology.

[88]  L. Hornez,et al.  Increased concentrations of the circulating angiogenesis inhibitor endostatin in patients with systemic sclerosis. , 2000, Arthritis and rheumatism.

[89]  Terence P. Speed,et al.  A comparison of normalization methods for high density oligonucleotide array data based on variance and bias , 2003, Bioinform..

[90]  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.

[91]  A. Bowcock,et al.  Insights into psoriasis and other inflammatory diseases from large-scale gene expression studies. , 2001, Human molecular genetics.

[92]  D. Strehlow The promise of transcription profiling for understanding the pathogenesis of scleroderma , 2000, Current rheumatology reports.

[93]  S. Skurkovich,et al.  The probable role of interferon in allergy. , 1975, Annals of allergy.

[94]  Thomas M. Aune,et al.  Cutting Edge: Molecular Portrait of Human Autoimmune Disease1 , 2002, The Journal of Immunology.

[95]  M. Feldmann,et al.  Immunoregulatory role of interleukin 10 in rheumatoid arthritis , 1994, The Journal of experimental medicine.

[96]  Luis Soares,et al.  An array of possibilities for the study of autoimmunity , 2005, Nature.

[97]  M. Feldmann,et al.  Synergy between anti-CD4 and anti-tumor necrosis factor in the amelioration of established collagen-induced arthritis. , 1994, Proceedings of the National Academy of Sciences of the United States of America.

[98]  J. Ortonne [Psoriasis, metabolic syndrome and its components]. , 2008, Annales de dermatologie et de venereologie.

[99]  J. Saurat,et al.  Efficacy and safety results from the randomized controlled comparative study of adalimumab vs. methotrexate vs. placebo in patients with psoriasis (CHAMPION) , 2007, The British journal of dermatology.

[100]  P. Miossec,et al.  Human interleukin-17: A T cell-derived proinflammatory cytokine produced by the rheumatoid synovium. , 1999, Arthritis and rheumatism.

[101]  C. Gabay,et al.  At the horizon of innovative therapy in rheumatology: new biologic agents , 2008, Current opinion in rheumatology.

[102]  P. Brown,et al.  Autoantigen microarrays for multiplex characterization of autoantibody responses , 2002, Nature Medicine.

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

[104]  P. Kivisäkk,et al.  Interleukin-17 mRNA expression in blood and CSF mononuclear cells is augmented in multiple sclerosis , 1999, Multiple sclerosis.

[105]  R. Silver,et al.  Scleroderma bronchoalveolar lavage fluid contains thrombin, a mediator of human lung fibroblast proliferation via induction of platelet-derived growth factor alpha-receptor. , 1994, American journal of respiratory cell and molecular biology.

[106]  A. Gurney,et al.  Interleukin-23 Promotes a Distinct CD4 T Cell Activation State Characterized by the Production of Interleukin-17* , 2003, The Journal of Biological Chemistry.

[107]  S. Jonjić,et al.  Site-restricted persistent cytomegalovirus infection after selective long-term depletion of CD4+ T lymphocytes , 1989, The Journal of experimental medicine.

[108]  M. Crow,et al.  Functional assay of type I interferon in systemic lupus erythematosus plasma and association with anti-RNA binding protein autoantibodies. , 2006, Arthritis and rheumatism.

[109]  Timothy W Behrens,et al.  Gene expression profiling in human autoimmunity , 2006, Immunological reviews.

[110]  Ash A. Alizadeh,et al.  The lymphochip: a specialized cDNA microarray for the genomic-scale analysis of gene expression in normal and malignant lymphocytes. , 1999, Cold Spring Harbor symposia on quantitative biology.

[111]  E. Pereira,et al.  Immunosuppressive therapy modulates T lymphocyte gene expression in patients with systemic lupus erythematosus , 2004, Immunology.

[112]  Maqc Consortium The MicroArray Quality Control (MAQC) project shows inter- and intraplatform reproducibility of gene expression measurements , 2006, Nature Biotechnology.

[113]  H. Makino,et al.  CD14+,CD16+ blood monocytes and joint inflammation in rheumatoid arthritis. , 2002, Arthritis and rheumatism.

[114]  V. Pascual,et al.  Role of interleukin-1 (IL-1) in the pathogenesis of systemic onset juvenile idiopathic arthritis and clinical response to IL-1 blockade , 2005, The Journal of experimental medicine.

[115]  R. Holmdahl,et al.  Genetic linkage analysis of collagen‐induced arthritis in the mouse , 1998, European journal of immunology.

[116]  A. Goris,et al.  IFNG polymorphisms are associated with gender differences in susceptibility to multiple sclerosis , 2005, Genes and Immunity.

[117]  Mark Lebwohl,et al.  Psoriasis , 1906, The Lancet.

[118]  M. Genovese,et al.  Combination therapy with etanercept and anakinra in the treatment of patients with rheumatoid arthritis who have been treated unsuccessfully with methotrexate. , 2004, Arthritis and rheumatism.

[119]  D. M. van der Heijde,et al.  Study of active controlled monotherapy used for rheumatoid arthritis, an IL-6 inhibitor (SAMURAI): evidence of clinical and radiographic benefit from an x ray reader-blinded randomised controlled trial of tocilizumab , 2007, Annals of the rheumatic diseases.

[120]  L. Joosten,et al.  Association of interleukin-18 expression with enhanced levels of both interleukin-1beta and tumor necrosis factor alpha in knee synovial tissue of patients with rheumatoid arthritis. , 2003, Arthritis and rheumatism.

[121]  L. Su Updates on high-throughput molecular profiling for the study of rheumatoid arthritis. , 2008, The Israel Medical Association journal : IMAJ.

[122]  Wing Hung Wong,et al.  Novel mechanisms of T-cell and dendritic cell activation revealed by profiling of psoriasis on the 63,100-element oligonucleotide array. , 2003, Physiological genomics.

[123]  Y. Kadono,et al.  Th17 functions as an osteoclastogenic helper T cell subset that links T cell activation and bone destruction , 2006, The Journal of experimental medicine.

[124]  John Quackenbush Microarray data normalization and transformation , 2002, Nature Genetics.

[125]  M. V. von Herrath,et al.  Initiation of autoimmunity. , 2004, Current opinion in immunology.

[126]  T. Mcclanahan,et al.  Divergent Pro- and Antiinflammatory Roles for IL-23 and IL-12 in Joint Autoimmune Inflammation , 2003, The Journal of experimental medicine.

[127]  E. Gelfand,et al.  Identification of Multiple Cell Cycle Regulatory Functions of p57Kip2 in Human T Lymphocytes1 , 2004, The Journal of Immunology.

[128]  W. Maśliński,et al.  High Levels of IL-17 in Rheumatoid Arthritis Patients: IL-15 Triggers In Vitro IL-17 Production Via Cyclosporin A-Sensitive Mechanism1 , 2000, The Journal of Immunology.

[129]  K. Kurz,et al.  Preliminary results of safety and efficacy of the interleukin 1 receptor antagonist anakinra in patients with severe lupus arthritis , 2004, Annals of the rheumatic diseases.

[130]  C. White,et al.  Rituximab: expanding role in therapy for lymphomas and autoimmune diseases. , 2004, Annual review of medicine.

[131]  F. Brennan,et al.  Update on cytokines in rheumatoid arthritis , 2007, Current opinion in rheumatology.

[132]  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.

[133]  L. Chatenoud Immune therapies of autoimmune diseases: are we approaching a real cure? , 2006, Current opinion in immunology.

[134]  D. Lockhart,et al.  Expression monitoring by hybridization to high-density oligonucleotide arrays , 1996, Nature Biotechnology.

[135]  V. Pascual,et al.  Systemic lupus erythematosus: all roads lead to type I interferons. , 2006, Current opinion in immunology.

[136]  M. Feldmann,et al.  Development of anti-TNF therapy for rheumatoid arthritis , 2002, Nature Reviews Immunology.

[137]  S. Brunak,et al.  Blood cell gene expression profiling in rheumatoid arthritis. Discriminative genes and effect of rheumatoid factor. , 2004, Immunology letters.

[138]  C. Herzog,et al.  Psoriasis: a possible risk factor for development of coronary artery calcification , 2007, The British journal of dermatology.

[139]  C. Putterman,et al.  Gene expression profiling in the study of the pathogenesis of systemic lupus erythematosus. , 2004, Autoimmunity reviews.

[140]  S. Skurkovich,et al.  Immunosuppressive Effect of an Anti-interferon Serum , 1974, Nature.

[141]  A. Achiron,et al.  Autoimmunity gene expression portrait: specific signature that intersects or differentiates between multiple sclerosis and systemic lupus erythematosus , 2004, Clinical and experimental immunology.

[142]  P. Calabresi,et al.  Characterization of MRI response to treatment with interferon beta-1b: Contrast-enhancing MRI lesion frequency as a primary outcome measure , 1997, Neurology.

[143]  F. Nestle,et al.  Infliximab induction and maintenance therapy for moderate-to-severe psoriasis: a phase III, multicentre, double-blind trial , 2005, The Lancet.

[144]  J. Edwards,et al.  B-cell targeting in rheumatoid arthritis and other autoimmune diseases , 2006, Nature Reviews Immunology.

[145]  Z Domljan,et al.  Treatment of rheumatoid arthritis with recombinant human interleukin-1 receptor antagonist. , 1998, Arthritis and rheumatism.

[146]  E. Bargagli,et al.  Cytokine profile and proteome analysis in bronchoalveolar lavage of patients with sarcoidosis, pulmonary fibrosis associated with systemic sclerosis and idiopathic pulmonary fibrosis , 2005, Proteomics.

[147]  A. Tobin,et al.  Spontaneous loss of T-cell tolerance to glutamic acid decarboxylase in murine insulin-dependent diabetes , 1993, Nature.

[148]  C. Gordon,et al.  Early rheumatoid arthritis is characterized by a distinct and transient synovial fluid cytokine profile of T cell and stromal cell origin , 2005, Arthritis research & therapy.

[149]  J. Smolen,et al.  Cytokines as therapeutic targets: advances and limitations. , 2008, Immunity.

[150]  M. Mayes,et al.  Classification analysis of the transcriptosome of nonlesional cultured dermal fibroblasts from systemic sclerosis patients with early disease. , 2005, Arthritis and rheumatism.

[151]  M. D. de Rie,et al.  The pathogenesis of psoriasis: immunological facts and speculations. , 1999, Immunology today.

[152]  Luting Xu,et al.  Human lupus T cells resist inactivation and escape death by upregulating COX-2 , 2004, Nature Medicine.

[153]  Reinhard Guthke,et al.  Gene expression profiling of peripheral blood mononuclear leukocytes from psoriasis patients identifies new immune regulatory molecules. , 2005, European journal of dermatology : EJD.

[154]  M. Crow Interferon pathway activation in systemic lupus erythematosus , 2005, Current rheumatology reports.

[155]  M. Feldmann,et al.  Role of cytokines in rheumatoid arthritis: an education in pathophysiology and therapeutics , 2008, Immunological reviews.

[156]  T. Olsson,et al.  Genetics of autoimmune neuroinflammation. , 2006, Current opinion in immunology.

[157]  H. Weiner,et al.  IL-23 Is Increased in Dendritic Cells in Multiple Sclerosis and Down-Regulation of IL-23 by Antisense Oligos Increases Dendritic Cell IL-10 Production , 2006, The Journal of Immunology.

[158]  Brian P. Dalrymple,et al.  A rapid method for computationally inferring transcriptome coverage and microarray sensitivity , 2005, Bioinform..

[159]  P. Mease Assessment tools in psoriatic arthritis. , 2008, The Journal of rheumatology.

[160]  Ash A. Alizadeh,et al.  Rheumatoid arthritis is a heterogeneous disease: evidence for differences in the activation of the STAT-1 pathway between rheumatoid tissues. , 2003, Arthritis and rheumatism.