Skip to main content
SpringerLink
Log in

Transcriptome Profiling in Autoimmune Diseases

  • Chapter
  • First Online:
Transcriptomics in Health and Disease

  • 1053 Accesses

Abstract

Autoimmune diseases are a group of different inflammatory disorders characterized by systemic or localized inflammation, affecting approximately 0.1–1 % of the general population. Several studies suggest that genetic risk loci are shared between different autoimmune diseases and pathogenic mechanisms may also be shared. The strategy of performing differential gene expression profiles in autoimmune disorders has unveiled new transcripts that may be shared among these disorders. Microarray technology and bioinformatics offer the most comprehensive molecular evaluations and it is widely used to understand the changes in gene expression in specific organs or in peripheral blood cells. The major goal of transcriptome studies is the identification of specific biomarkers for different diseases. It is believed that such knowledge will contribute to the development of new drugs, new strategies for early diagnosis, avoiding tissue autoimmune destruction, or even preventing the development of autoimmune disease. In this review, we primarily focused on the transcription profiles of three typical autoimmune disorders, including type 1 diabetes mellitus (destruction of pancreatic islet beta cells), systemic lupus erythematosus (immune complex systemic disorder affecting several organs and tissues) and multiple sclerosis (inflammatory and demyelinating disease of the central nervous system).

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 119.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 159.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

Similar content being viewed by others

References

  • Achenbach P, Warncke K, Reiter J et al (2004) Stratification of type 1 diabetes risk on the basis of islet autoantibody characteristics. Diabetes 53:384–392

    CAS  PubMed  Google Scholar 

  • Baechler EC, Batliwalla FM, Karypis G et al (2003) Interferon-inducible gene expression signature in peripheral blood cells of patients with severe lupus. Poc Natl Acad Sci U S A 100:2610–2615

    CAS  Google Scholar 

  • Barcellos LF, Oksenberg JR, Begovich AB et al (2003) HLA-DR2 dose effect on susceptibility to multiple sclerosis and influence on disease course. Am J Hum Genet 72:710–716

    CAS  PubMed Central  PubMed  Google Scholar 

  • Barrett JC, Clayton DG, Concannon P et al (2009) Genome-wide association study and meta-analysis find that over 40 loci affect risk of type 1 diabetes. Nat Genet 41:703–707

    CAS  PubMed Central  PubMed  Google Scholar 

  • Battaglia M (2014) Neutrophils and type 1 autoimmune diabetes. Curr Opin Hematol 21:8–15

    CAS  PubMed  Google Scholar 

  • Beall SS, Biddison WE, McFarlin DE et al (1993) Susceptibility for multiple sclerosis is determined, in part, by inheritance of a 175-kb region of the TcR V beta chain locus and HLA class II genes. J Neuroimmunol 45:53–60

    CAS  PubMed  Google Scholar 

  • Bengtsson AA, Sturfelt G, Truedsson L et al (2000) Activation of type I interferon system in systemic lupus erythematosus correlates with disease activity but not with antiretroviral antibodies. Lupus 9:664–671

    CAS  PubMed  Google Scholar 

  • Bennett L, Palucka AK, Arce E et al (2003) Interferon and granulopoiesis signatures in systemic lupus erythematosus blood. J Exp Med 197:711–723

    CAS  PubMed  Google Scholar 

  • Berndt JA, Kim JG, Tosic M et al (2001) The transcriptional regulator Yin Yang 1 activates the myelin PLP gene. J Neurochem 77:935–942

    CAS  PubMed  Google Scholar 

  • Bertsias GK, Salmon JE, Boumpas DT (2010) Therapeutic opportunities in systemic lupus erythematosus: state of the art and prospects for the new decade. Ann Rheum Dis 69:1603–1611

    PubMed  Google Scholar 

  • Bomprezzi R, Ringner M, Kim S et al (2003) Gene expression profile in multiple sclerosis patients and healthy controls: identifying pathways relevant to disease. Hum Mol Genet 12:2191–2199

    CAS  PubMed  Google Scholar 

  • Borjabad A, Volsky DJ (2012) Common transcriptional signatures in brain tissue from patients with HIV-associated neurocognitive disorders, alzheimer’s disease, and multiple sclerosis. J Neuroimmune Pharmacol 7:914–926

    PubMed Central  PubMed  Google Scholar 

  • Brum DG, Barreira AA, Louzada-Junior P et al (2007) Association of the HLA-DRB1*15 allele group and the DRB1*1501 and DRB1*1503 alleles with multiple sclerosis in White and Mulatto samples from Brazil. J Neuroimmunol 189:118–124

    CAS  PubMed  Google Scholar 

  • Brynedal B, Khademi M, Wallstrom E et al (2010) Gene expression profiling in multiple sclerosis: a disease of the central nervous system, but with relapses triggered in the periphery? Neurobiol Dis 37:613–621

    CAS  PubMed  Google Scholar 

  • Burgos P, Metz C, Bull P et al (2000) Increased expression of c-rel, from the NF-KB/Rel family, in T cells from patients with systemic lupus erythematosus. J Rheumatol 27:116–127

    CAS  PubMed  Google Scholar 

  • Buschard K (2011) What causes type 1 diabetes? Lessons from animal models. APMIS Suppl 119(132):1–19

    Google Scholar 

  • Carlsen AL, Schetter AJ, Nielsen CT et al (2013) Circulating microRNA expression profiles associated with systemic lupus erythematosus. Arthritis Rheum 65:1324–1334

    CAS  PubMed  Google Scholar 

  • Chan AC, Iwashima M, Turck CW et al (1992) ZAP-70: a 70 kd protein-tyrosine kinase that associates with the TCR zeta chain. Cell 71:649–662

    CAS  PubMed  Google Scholar 

  • Chan RW, Lai FM, Li EK et al (2006) Imbalance of Th1/Th2 transcription factors in patients with lupus nephritis. Rheumatology (Oxford) 45:951–957

    CAS  Google Scholar 

  • Chentoufi AA, Binder NR, Berka N et al (2008) Advances in type I diabetes associated tolerance mechanisms. Scand J Immunol 68:1–11

    CAS  PubMed  Google Scholar 

  • Chitnis T (2007) The role of CD4 T cells in the pathogenesis of multiple sclerosis. Int Rev Neurobiol 79:43–72

    CAS  PubMed  Google Scholar 

  • Cho JH, Gregersen PK (2011) Genomics and the multifactorial nature of human autoimmune disease. N Engl J Med 365:1612–1623

    CAS  PubMed  Google Scholar 

  • Chora AA, Fontoura P, Cunha A et al (2007) Heme oxygenase-1 and carbon monoxide suppress autoimmune neuroinflammation. J Clin Invest 117:438–447

    CAS  PubMed Central  PubMed  Google Scholar 

  • Cipolletta C, Ryan KE, Hanna EV et al (2005) Activation of peripheral blood CD14+ monocytes occurs in diabetes. Diabetes 54:2779–2786

    CAS  PubMed  Google Scholar 

  • Collares CV, Evangelista AF, Xavier DJ et al (2013a) Transcriptome meta-analysis of peripheral lymphomononuclear cells indicates that gestational diabetes is closer to type 1 diabetes than to type 2 diabetes mellitus. Mol Biol Rep 40:5351–5358

    Google Scholar 

  • Collares CV, Evangelista AF, Xavier DJ et al (2013b) Identifying common and specific microRNAs expressed in peripheral blood mononuclear cell of type 1, type 2, and gestational diabetes mellitus patients. BMC Res Notes 6:491

    Google Scholar 

  • Colli ML, Moore F, Gurzov EN et al (2010) MDA5 and PTPN2, two candidate genes for type 1 diabetes, modify pancreatic b-cell responses to the viral by-product double-stranded RNA. Hum Mol Genet 19:135–146

    CAS  PubMed Central  PubMed  Google Scholar 

  • Concannon P, Rich SS, Nepom GT (2009) Genetics of type 1A diabetes. N Engl J Med 360:1646–1654

    CAS  PubMed  Google Scholar 

  • Costa V, Aprile M, Esposito R et al (2013) RNA-Seq and human complex diseases: recent accomplishments and future perspectives. Eur J Hum Genet 21:134–142

    CAS  PubMed Central  PubMed  Google Scholar 

  • Cox MB, Cairns MJ, Gandhi KS et al (2010) MicroRNAs miR-17 and miR-20a inhibit T cell activation genes and are under-expressed in MS whole blood. PLoS One 5:e12132

    PubMed Central  PubMed  Google Scholar 

  • Crow MK (2008) Collaboration, genetic associations, and lupus erythematosus. N Engl J Med 358:956–961

    CAS  PubMed  Google Scholar 

  • Crow MK, Kirou KA (2004) Interferon-alpha in systemic lupus erythematosus. Curr Opin Rheumatol 16:541–547

    CAS  PubMed  Google Scholar 

  • Crow MK, Wohlgemuth J (2003) Microarray analysis of gene expression in lupus. Arthritis Res Ther 5:279–287

    CAS  PubMed Central  PubMed  Google Scholar 

  • Dai Y, Huang YS, Tang M et al (2007) Microarray analysis of microRNA expression in peripheral blood cells of systemic lupus erythematosus patients. Lupus 16:939–946

    CAS  PubMed  Google Scholar 

  • De Santis G, Ferracin M, Biondani A et al (2010) Altered miRNA expression in T regulatory cells in course of multiple sclerosis. J Neuroimmunol 226:165–171

    PubMed  Google Scholar 

  • Deapen D, Escalante A, Weinrib L et al (1992) A revised estimate of twin concordance in systemic lupus erythematosus. Arthritis Rheum 35:311–318

    CAS  PubMed  Google Scholar 

  • Deng Y, Tsao BP (2010) Genetic susceptibility to systemic lupus erythematosus in the genomic era. Nat Rev Rheumatol 6:683–692

    CAS  PubMed Central  PubMed  Google Scholar 

  • Deng C, Kaplan MJ, Yang J et al (2001) Decreased Ras-mitogen-activated protein kinase signaling may cause DNA hypomethylation in T lymphocytes from lupus patients. Arthritis Rheum 44:397–407

    CAS  PubMed  Google Scholar 

  • Dib SA (2008) Heterogeneity of type 1 diabetes mellitus. Arq Bras Endocrinol Metabol 52:205–218

    PubMed  Google Scholar 

  • Doria A, Canova M, Tonon M et al (2008) Infections as triggers and complications of systemic lupus erythematosus. Autoimmun Rev 8:24–28

    CAS  PubMed  Google Scholar 

  • Du C, Liu C, Kang J et al (2009) MicroRNA miR-326 regulates TH-17 differentiation and is associated with the pathogenesis of multiple sclerosis. Nat Immunol 10:1252–1259

    CAS  PubMed  Google Scholar 

  • Dumortier O, Van Obberghen E (2012) MicroRNAs in pancreas development. Diabetes Obes Metab 14(Suppl 3):22–28

    CAS  PubMed  Google Scholar 

  • Dyment DA, Ebers GC, Sadovnick AD (2004) Genetics of multiple sclerosis. Lancet Neurol 3:104–110

    CAS  PubMed  Google Scholar 

  • Eizirik DL, Colli ML, Ortis F (2009) The role of inflammation in insulitis and b-cell loss in type 1 diabetes. Nat Rev Endocrinol 5:219–226

    CAS  PubMed  Google Scholar 

  • Eizirik DL, Sammeth M, Bouckenooghe T et al (2012) The human pancreatic islet transcriptome: expression of candidate genes for type 1 diabetes and the impact of pro-inflammatory cytokines. PLoS Genet 8:e1002552

    CAS  PubMed Central  PubMed  Google Scholar 

  • El Ouaamari A, Baroukh N, Martens GA et al (2008) MiR-375 targets 3’-phosphoinositide-dependent protein kinase-1 and regulates glucose-induced biological responses in pancreatic beta-cells. Diabetes 57:2708–2017

    PubMed Central  PubMed  Google Scholar 

  • Epplen C, Jackel S, Santos EJ et al (1997) Genetic predisposition to multiple sclerosis as revealed by immunoprinting. Ann Neurol 41:341–352

    CAS  PubMed  Google Scholar 

  • Erlich H, Valdes AM, Noble J et al (2008) HLA DR-DQ haplotypes and genotypes and type 1 diabetes risk: analysis of the type 1 diabetes genetics consortium families. (Type 1 Diabetes Genetics Consortium). Diabetes 57:1084–1092

    CAS  PubMed Central  PubMed  Google Scholar 

  • Evangelista AF, Collares CVA, Xavier DJ et al (2014) Integrative analysis of the transcriptome profiles observed in type 1, type 2 and gestational diabetes mellitus reveals the role of inflammation. BMC Med Genomics 7:28

    PubMed Central  PubMed  Google Scholar 

  • Feng X, Wu H, Grossman JM et al (2006) Association of increased interferon-inducible gene expression with disease activity and lupus nephritis in patients with systemic lupus erythematosus. Arthritis Rheum 54:2951–2962

    CAS  PubMed  Google Scholar 

  • Fenoglio C, Ridolfi E, Cantoni C et al (2013) Decreased circulating miRNA levels in patients with primary progressive multiple sclerosis. Mult Scler 19:1938–1942

    CAS  PubMed  Google Scholar 

  • Fornari TA, Donate PB, Macedo C et al (2011) Development of type 1 diabetes mellitus in nonobese diabetic mice follows changes in thymocyte and peripheral T lymphocyte transcriptional activity. Clin Dev Immunol 2011:158735

    PubMed Central  PubMed  Google Scholar 

  • Foster MH, Kelley VR (1999) Lupus nephritis: update on pathogenesis and disease mechanisms. Semin Nephrol 19:173–181

    CAS  PubMed  Google Scholar 

  • Frost RJ, Olson EN (2011) Control of glucose homeostasis and insulin sensitivity by the Let-7 family of microRNAs. Proc Natl Acad Sci U S A 108:21075–21080

    CAS  PubMed Central  PubMed  Google Scholar 

  • Frota ER, Rodrigues DH, Donadi EA et al (2009) Increased plasma levels of brain derived neurotrophic factor (BDNF) after multiple sclerosis relapse. Neurosci Lett 460:130–132

    CAS  PubMed  Google Scholar 

  • Furukawa H, Oka S, Matsui T et al (2013) Genome, epigenome and transcriptome analyses of a pair of monozygotic twins discordant for systemic lupus erythematosus. Hum Immunol 74:170–175

    CAS  PubMed  Google Scholar 

  • Geenen V, Mottet M, Dardenne O et al (2010) Thymic self-antigens for the design of a negative/tolerogenic self-vaccination against type 1 diabetes. Curr Opin Pharmacol 10:461–472

    CAS  PubMed  Google Scholar 

  • Grammatikos AP, Kyttaris VC, Kis-Toth K et al (2014) A T cell gene expression panel for the diagnosis and monitoring of disease activity in patients with systemic lupus erythematosus. Clin Immunol 150:192–200

    CAS  PubMed  Google Scholar 

  • Grinberg-Bleyer Y, Baeyens A, You S et al (2010) IL-2 reverses established type 1 diabetes in NOD mice by a local effect on pancreatic regulatory T cells. J Exp Med 207:1871–1878

    CAS  PubMed Central  PubMed  Google Scholar 

  • Guerra SG, Vyse TJ, Cunninghame Graham DS (2012) The genetics of lupus: a functional perspective. Arthritis Res Ther 14:211

    PubMed Central  PubMed  Google Scholar 

  • Guo J, Casolaro V, Seto E et al (2001) Yin-Yang 1 activates interleukin-4 gene expression in T cells. J Biol Chem 276:48871–48878

    CAS  PubMed  Google Scholar 

  • Guo J, Lin X, Williams MA et al (2008) Yin-Yang 1 regulates effector cytokine gene expression and T(H)2 immune responses. J Allergy Clin Immunol 122:195–201

    CAS  PubMed  Google Scholar 

  • Gurevich M, Achiron A (2012) The switch between relapse and remission in multiple sclerosis: continuous inflammatory response balanced by Th1 suppression and neurotrophic factors. J Neuroimmunol 252:83–88

    CAS  PubMed  Google Scholar 

  • Han GM, Chen SL, Shen N et al (2003) Analysis of gene expression profiles in human systemic lupus erythematosus using oligonucleotide microarray. Genes Immun 4:177–186

    CAS  PubMed  Google Scholar 

  • Han D, Leyva CA, Matheson D et al (2011) Immune profiling by multiple gene expression analysis in patients at-risk and with type 1 diabetes. Clin Immunol 139:290–301

    CAS  PubMed Central  PubMed  Google Scholar 

  • Hecker M, Thamilarasan M, Koczan D et al (2013) MicroRNA expression changes during interferon-beta treatment in the peripheral blood of multiple sclerosis patients. Int J Mol Sci 14:16087–16110

    PubMed Central  PubMed  Google Scholar 

  • Hennessy E, Clynes M, Jeppesen PB et al (2010) Identification of microRNAs with a role in glucose stimulated insulin secretion by expression profiling of MIN6 cells. Biochem Biophys Res Commun 396:457–462

    CAS  PubMed  Google Scholar 

  • Herold KC, Brooks-Worrell B, Palmer J et al (2009) Validity and reproducibility of measurement of islet autoreactivity by T-cell assays in subjects with early type 1 diabetes. Diabetes 58:2588–2595

    CAS  PubMed Central  PubMed  Google Scholar 

  • Holler CJ, Webb RL, Laux AL et al (2012) BACE2 expression increases in human neurodegenerative disease. Am J Pathol 180:337–350

    CAS  PubMed Central  PubMed  Google Scholar 

  • Islam T, Gauderman WJ, Cozen W et al (2006) Differential twin concordance for multiple sclerosis by latitude of birthplace. Ann Neurol 60:56–64

    PubMed  Google Scholar 

  • Jarvinen P, Kaprio J, Makitalo R et al (1992) Systemic lupus erythematosus and related systemic diseases in a nationwide twin cohort: an increased prevalence of disease in MZ twins and concordance of disease features. J Intern Med 231:67–72

    CAS  PubMed  Google Scholar 

  • Jayaraman S, Patel A, Jayaraman A et al (2013) Transcriptome analysis of epigenetically modulated genome indicates signature genes in manifestation of type 1 diabetes and its prevention in NOD mice. PLoS One 8:e55074

    CAS  PubMed Central  PubMed  Google Scholar 

  • Jernas M, Malmeström C, Axelsson M et al (2013) MS risk genes are transcriptionally regulated in CSF leukocytes at relapse. Mult Scler 19:403–410

    CAS  PubMed  Google Scholar 

  • Junker A, Krumbholz M, Eisele S et al (2009) MicroRNA profiling of multiple sclerosis lesions identifies modulators of the regulatory protein CD47. Brain 132:3342–3352

    PubMed  Google Scholar 

  • Kaimen-Maciel DR, Reiche EM, Borelli SD et al (2009) HLA-DRB1* allele-associated genetic susceptibility and protection against multiple sclerosis in Brazilian patients. Mol Med Rep 2:993–998

    CAS  PubMed  Google Scholar 

  • Kamradt T, Mitchison NA (2001) Tolerance and autoimmunity. N Engl J Med 344:655–664

    CAS  PubMed  Google Scholar 

  • Karpuj MV, Steinman L, Oksenberg JR (1997) Multiple sclerosis: a polygenic disease involving epistatic interactions, germline rearrangements and environmental effects. Neurogenetics 1:21–28

    CAS  PubMed  Google Scholar 

  • Karumuthil-Melethil S, Perez N, Li R et al (2008) Induction of innate immune response through TLR2 and dectin 1 prevents type 1 diabetes. J Immunol 181:8323–8334

    CAS  PubMed Central  PubMed  Google Scholar 

  • Kawai T, Akira S (2006) TLR signaling. Cell Death Differ 13:816–825

    CAS  PubMed  Google Scholar 

  • Keller A, Leidinger P, Lange J et al (2009) Multiple sclerosis: microRNA expression profiles accurately differentiate patients with relapsing remitting disease from healthy controls. PLoS One 4:e7440

    PubMed Central  PubMed  Google Scholar 

  • Keller A, Leidinger P, Steinmeyer F et al (2014) Comprehensive analysis of microRNA profiles in multiple sclerosis including next-generation sequencing. Mult Scler 20:295–303

    CAS  PubMed  Google Scholar 

  • Kilpinen H, Dermitzakis ET (2012) Genetic and epigenetic contribution to complex traits. Hum Mol Genet 21:R24–R28

    CAS  PubMed  Google Scholar 

  • Kirou KA, Lee C, George S et al (2004) Coordinate overexpression of interferon-alpha-induced genes in systemic lupus erythematosus. Arthritis Rheum 50:3958–3967

    CAS  PubMed  Google Scholar 

  • Kirou KA, Lee C, George S et al (2005) Activation of the interferon-alpha pathway identifies a subgroup of systemic lupus erythematosus patients with distinct serologic features and active disease. Arthritis Rheum 52:1491–1503

    CAS  PubMed  Google Scholar 

  • Knip M, Siljander H (2008) Autoimmune mechanisms in type 1 diabetes. Autoimmun Rev 7:550–557

    CAS  PubMed  Google Scholar 

  • Koga M, Kawasaki A, Ito I et al (2011) Cumulative association of eight susceptibility genes with systemic lupus erythematosus in a Japanese female population. J Hum Genet 56(7):503–507

    CAS  PubMed  Google Scholar 

  • Krützfeldt J, Stoffel M (2006) MicroRNAs: a new class of regulatory genes affecting metabolism. Cell Metab 4:9–12

    PubMed  Google Scholar 

  • Kuo CC, Lin SC (2007) Altered FOXO1 transcript levels in peripheral blood mononuclear cells of systemic lupus erythematosus and rheumatoid arthritis patients. Mol Med 13:561–566

    CAS  PubMed Central  PubMed  Google Scholar 

  • Laplaud DA, Ruiz C, Wiertlewski S et al (2004) Blood T-cell receptor beta chain transcriptome in multiple sclerosis. Characterization of the T cells with altered CDR3 length distribution. Brain 127:981–995

    PubMed  Google Scholar 

  • Lashine YA, Seoudi AM, Salah S et al (2011) Expression signature of microRNA-181-a reveals its crucial role in the pathogenesis of paediatric systemic lupus erythematosus. Clin Exp Rheumatol 29:351–357

    CAS  PubMed  Google Scholar 

  • Layer K, Lin G, Nencioni A et al (2003) Autoimmunity as the consequence of a spontaneous mutation in Rasgrp1. Immunity 19:243–255

    CAS  PubMed  Google Scholar 

  • Lee HM, Sugino H, Aoki C et al (2011) Underexpression of mitochondrial-DNA encoded ATP synthesis-related genes and DNA repair genes in systemic lupus erythematosus. Arthritis Res Ther 13:R63

    CAS  PubMed Central  PubMed  Google Scholar 

  • Li R, Perez N, Karumuthil-Melethil S et al (2007) Bone marrow is a preferential homing site for autoreactive T-cells in type 1 diabetes. Diabetes 56:2251–2259

    CAS  PubMed  Google Scholar 

  • Li QZ, Zhou J, Lian Y et al (2010) Interferon signature gene expression is correlated with autoantibody profiles in patients with incomplete lupus syndromes. Clin Exp Immunol 159:281–291

    CAS  PubMed Central  PubMed  Google Scholar 

  • Lindberg RL, Hoffmann F, Mehling M et al (2010) Altered expression of miR-17–5p in CD4+ lymphocytes of relapsing-remitting multiple sclerosis patients. Eur J Immunol 40:888–898

    CAS  PubMed  Google Scholar 

  • Lindén M, Khademi M, Lima Bomfim I et al (2013) Multiple sclerosis risk genotypes correlate with an elevated cerebrospinal fluid level of the suggested prognostic marker CXCL13. Mult Scler 19:863–870

    PubMed  Google Scholar 

  • Lit LC, Wong CK, Li EK et al (2007) Elevated gene expression of Th1/Th2 associated transcription factors is correlated with disease activity in patients with systemic lupus erythematosus. J Rheumatol 34:89–96

    CAS  PubMed  Google Scholar 

  • Liu Z, Davidson A (2012) Taming lupus—a new understanding of pathogenesis is leading to clinical advances. Nat Med 18:871–882

    PubMed Central  PubMed  Google Scholar 

  • Lood C, Amisten S, Gullstrand B et al (2010) Platelet transcriptional profile and protein expression in patients with systemic lupus erythematosus: up-regulation of the type I interferon system is strongly associated with vascular disease. Blood 116:1951–1957

    CAS  PubMed  Google Scholar 

  • Lu MC, Lai NS, Chen HC et al (2013) Decreased microRNA(miR)-145 and increased miR-224 expression in T cells from patients with systemic lupus erythematosus involved in lupus immunopathogenesis. Clin Exp Immunol 171:91–99

    CAS  PubMed Central  PubMed  Google Scholar 

  • Lublin FD, Reingold SC (1996) Defining the clinical course of multiple sclerosis: results of an international survey. Neurology 46:907–911

    CAS  PubMed  Google Scholar 

  • Lucchinetti CF, Brueck W, Rodriguez M et al (1998) Multiple sclerosis: lessons from neuropathology. Semin Neurol 18:337–349

    CAS  PubMed  Google Scholar 

  • Lyons PA, McKinney EF, Rayner TF et al (2010) Novel expression signatures identified by transcriptional analysis of separated leukocyte subsets in systemic lupus erythematosus and vasculitis. Ann Rheum Dis 69:1208–1213

    CAS  PubMed Central  PubMed  Google Scholar 

  • Maas K, Chen H, Shyr Yu et al (2005) Shared gene expression profiles in individuals with autoimmune disease and unaffected first-degree relatives of individuals with autoimmune disease. Hum Mol Genet 14:1305–1314

    CAS  PubMed  Google Scholar 

  • Mackay IR (2009) Clustering and commonalities among autoimmune diseases. J Autoimmun 33:170–177

    CAS  PubMed  Google Scholar 

  • Mattick JS, Makunin IV (2006) Non-coding RNA. Hum Mol Genet 15(Spec No 1):R17–R29

    CAS  PubMed  Google Scholar 

  • Mattick JS, Taft RJ, Faulkner GJ (2010) A global view of genomic information–moving beyond the gene and the master regulator. Trends Genet 26:21–28

    CAS  PubMed  Google Scholar 

  • Matzinger P (2002) The danger model: a renewed sense of self. Science 296:301–305

    CAS  PubMed  Google Scholar 

  • McDevitt HO, Unanue ER (2008) Autoimmune diabetes mellitus–much progress, but many challenges. Adv Immunol 100:1–12

    CAS  PubMed  Google Scholar 

  • Melief J, de Wit SJ, Van Eden CG et al (2013) HPA axis activity in multiple sclerosis correlates with disease severity, lesion type and gene expression in normal-appearing white matter. Acta Neuropathol 126:237–249

    PubMed  Google Scholar 

  • Melzer S, Michael M, Caputi A et al (2012) Long-range-projecting GABAergic neurons modulate inhibition in hippocampus and entorhinal cortex. Science 335:1506–1510

    CAS  PubMed  Google Scholar 

  • Moore F, Colli ML, Cnop M et al (2009) PTPN2, a candidate gene for type 1 diabetes, modulates interferon-gamma-induced pancreatic b-cell apoptosis. Diabetes 58:1283–1291

    CAS  PubMed Central  PubMed  Google Scholar 

  • Moore CS, Rao VT, Durafourt BA et al (2013) miR-155 as a multiple sclerosis-relevant regulator of myeloid cell polarization. Ann Neurol 74:709–720

    CAS  PubMed  Google Scholar 

  • Moser KL, Kelly JA, Lessard CJ et al (2009) Recent insights into the genetic basis of systemic lupus erythematosus. Genes Immun 10:373–379

    CAS  PubMed Central  PubMed  Google Scholar 

  • Mumford CJ, Wood NW, Kellar-Wood H et al (1994) The British Isles survey of multiple sclerosis in twins. Neurology 44:11–15

    CAS  PubMed  Google Scholar 

  • Nakou M, Knowlton N, Frank MB et al (2008) Gene expression in systemic lupus erythematosus: bone marrow analysis differentiates active from inactive disease and reveals apoptosis and granulopoiesis signatures. Arthritis Rheum 58(11):3541–3549

    CAS  PubMed Central  PubMed  Google Scholar 

  • Nakou M, Bertsias G, Stagakis I et al (2010) Gene network analysis of bone marrow mononuclear cells reveals activation of multiple kinase pathways in human systemic lupus erythematosus. PLoS One 5:e13351

    PubMed Central  PubMed  Google Scholar 

  • Nerup J, Nierras C, Plagnol V et al (2009) Genome-wide association study and meta-analysis find that over 40 loci affect risk of type 1 diabetes. Nat Genet 41:703–707

    PubMed Central  PubMed  Google Scholar 

  • Nielsen NM, Westergaard T, Rostgaard K et al (2005) Familial risk of multiple sclerosis: a nationwide cohort study. Am J Epidemiol 162:774–778

    PubMed  Google Scholar 

  • Niewold TB, Swedler WI (2005) Systemic lupus erythematosus arising during interferon-alpha therapy for cryoglobulinemic vasculitis associated with hepatitis C. Clin Rheumatol 24:178–181

    PubMed  Google Scholar 

  • Niewold TB, Hua J, Lehman TJ et al (2007) High serum IFN-alpha activity is a heritable risk factor for systemic lupus erythematosus. Genes Immun 8:492–502

    CAS  PubMed Central  PubMed  Google Scholar 

  • Noorbakhsh F, Ellestad KK, Maingat F et al (2011) Impaired neurosteroid synthesis in multiple sclerosis. Brain 134:2703–2721

    PubMed Central  PubMed  Google Scholar 

  • Noseworthy JH, Lucchinetti C, Rodriguez M et al (2000) Multiple sclerosis. N Engl J Med 343:938–952

    CAS  PubMed  Google Scholar 

  • Novak J, Lehuen A (2011) Mechanism of regulation of autoimmunity by iNKT cells. Cytokine 53:263–270

    CAS  PubMed  Google Scholar 

  • Oh J, Broyles SS (2005) Host cell nuclear proteins are recruited to cytoplasmic vaccinia virus replication complexes. J Virol 79:12852–12860

    CAS  PubMed Central  PubMed  Google Scholar 

  • Oksenberg JR, Baranzini SE, Sawcer S et al (2008) The genetics of multiple sclerosis: SNPs to pathways to pathogenesis. Nature Rev Genet 9:516–526

    CAS  PubMed  Google Scholar 

  • Pan W, Zhu S, Yuan M et al (2010) MicroRNA-21 and microRNA-148a contribute to DNA hypomethylation in lupus CD4+ T cells by directly and indirectly targeting DNA methyltransferase 1. J Immunol 184:6773–6781

    CAS  PubMed  Google Scholar 

  • Petri M (1995) Clinical features of systemic lupus erythematosus. Curr Opin Rheumatol 7:395–401

    CAS  PubMed  Google Scholar 

  • Plagnol V, Howson JM, Smyth DJ et al (2011) Genome-wide association analysis of autoantibody positivity in type 1 diabetes cases. PLoS Genet 7:e1002216

    CAS  PubMed Central  PubMed  Google Scholar 

  • Plaisance V, Abderrahmani A, Perret-Menoud V et al (2006) MicroRNA-9 controls the expression of granuphilin/Slp4 and the secretory response of insulin-producing cells. J Biol Chem 281:26932–26942

    CAS  PubMed  Google Scholar 

  • Planas R, Pujol-Borrell R, Vives-Pi M (2010) Global gene expression changes in type 1 diabetes: insights into autoimmune response in the target organ and in the periphery. Immunol Lett 133:55–61

    CAS  PubMed  Google Scholar 

  • Pociot F, Akolkar B, Concannon P et al (2010) Genetics of type 1 diabetes: what’s next? Diabetes 59:1561–1571

    CAS  PubMed Central  PubMed  Google Scholar 

  • Ponting CP, Oliver PL, Reik W (2009) Evolution and functions of long noncoding RNAs. Cell 136:629–641

    CAS  PubMed  Google Scholar 

  • Poo MM (2001) Neurotrophins as synaptic modulators. Nat Rev Neurosci 2:24–32

    CAS  PubMed  Google Scholar 

  • Poy MN, Eliasson L, Krutzfeldt J et al (2004) A pancreatic islet-specific microRNA regulates insulin secretion. Nature 432:226–230

    CAS  PubMed  Google Scholar 

  • Pugliese A, Miceli D (2002) The insulin gene in diabetes. Diabetes Metab Res Rev 18:13–25

    CAS  PubMed  Google Scholar 

  • Purohit S, She JX (2008) Biomarkers for type 1 diabetes. Int J Clin Exp Med 1:98–116

    CAS  PubMed Central  PubMed  Google Scholar 

  • Qin H, Zhu X, Liang J et al (2013) MicroRNA-29b contributes to DNA hypomethylation of CD4+ T cells in systemic lupus erythematosus by indirectly targeting DNA methyltransferase 1. J Dermatol Sci 69:61–67

    CAS  PubMed  Google Scholar 

  • Rassi DM, Junta CM, Fachin AL et al (2008) Gene expression profiles stratified according to type 1 diabetes mellitus susceptibility regions. Ann N Y Acad Sci 1150:282–289

    CAS  PubMed  Google Scholar 

  • Remoli ME, Ragimbeau J, Giacomini E et al (2007) NF-{kappa}B is required for STAT-4 expression during dendritic cell maturation. J Leukoc Biol 81:355–363

    CAS  PubMed  Google Scholar 

  • Reynier F, Pachot A, Paye M et al (2010) Specific gene expression signature associated with development of autoimmune type-I diabetes using whole-blood microarray analysis. Genes Immun 11:269–278

    CAS  PubMed  Google Scholar 

  • Ridolfi E, Fenoglio C, Cantoni C et al (2013) Expression and genetic analysis of MicroRNAs involved in multiple sclerosis. Int J Mol Sci 14:4375–4384

    CAS  PubMed Central  PubMed  Google Scholar 

  • Riveros C, Mellor D, Gandhi KS et al (2010) A transcription factor map as revealed by a genome-wide gene expression analysis of whole-blood mRNA transcriptome in multiple sclerosis. PLoS One 5:e14176

    PubMed Central  PubMed  Google Scholar 

  • Ronnblom LE, Alm GV, Oberg KE (1990) Possible induction of systemic lupus erythematosus by interferon-alpha treatment in a patient with a malignant carcinoid tumour. J Intern Med 227:207–210

    CAS  PubMed  Google Scholar 

  • Rus V, Chen H, Zernetkina V et al (2004) Gene expression profiling in peripheral blood mononuclear cells from lupus patients with active and inactive disease. Clin Immunol 112:231–234

    CAS  PubMed  Google Scholar 

  • Sadovnick AD, Ebers GC (1993) Epidemiology of multiple sclerosis: a critical overview. Can J Neurol Sci 20:17–29

    CAS  PubMed  Google Scholar 

  • Sadovnick AD, Ebers GC, Dyment DA et al (1996) Evidence for genetic basis of multiple sclerosis. The Canadian Collaborative Study Group. Lancet 347:1728–1730

    CAS  PubMed  Google Scholar 

  • Santiago-Raber ML, Lawson BR, Dummer W et al (2001) Role of cyclin kinase inhibitor p21 in systemic autoimmunity. J Immunol 167:4067–4074

    CAS  PubMed  Google Scholar 

  • Santin I, Moore F, Colli ML et al (2011) PTPN2, a candidate gene for type 1 diabetes, modulates pancreatic β-cell apoptosis via regulation of the BH3-only protein Bim. Diabetes 60:3279–3288

    CAS  PubMed Central  PubMed  Google Scholar 

  • Satoh J, Misawa T, Tabunoki H et al (2008) Molecular network analysis of T-cell transcriptome suggests aberrant regulation of gene expression by NF-kappaB as a biomarker for relapse of multiple sclerosis. Dis Markers 25:27–35

    CAS  PubMed Central  PubMed  Google Scholar 

  • Schwartzman-Morris J, Putterman C (2012) Gender differences in the pathogenesis and outcome of lupus and of lupus nephritis. Clin Dev Immunol 2012:604892

    PubMed Central  PubMed  Google Scholar 

  • Shaw JE, Sicree RA, Zimmet PZ (2010) Global estimates of the prevalence of diabetes for 2010 and 2030. Diabetes Res Clin Pract 87:4–14

    CAS  PubMed  Google Scholar 

  • Sia C (2006) Replenishing peripheral CD4+ regulatory T cells: a possible immune-intervention strategy in type 1 diabetes? Rev Diabet Stud 3:102–107

    PubMed Central  PubMed  Google Scholar 

  • Sondergaard HB, Hesse D, Krakauer M et al (2013) Differential microRNA expression in blood in multiple sclerosis. Mult Scler 19:1849–1857

    CAS  PubMed  Google Scholar 

  • Stagakis E, Bertsias G, Verginis P et al (2011) Identification of novel microRNA signatures linked to human lupus disease activity and pathogenesis: miR-21 regulates aberrant T cell responses through regulation of PDCD4 expression. Ann Rheum Dis 70:1496–1506

    CAS  PubMed  Google Scholar 

  • Stone RC, Du P, Feng D et al (2013) RNA-Seq for enrichment and analysis of IRF5 transcript expression in SLE. PLoS One 8:e54487

    CAS  PubMed Central  PubMed  Google Scholar 

  • Straub RH (2007) The complex role of estrogens in inflammation. Endocr Rev 28:521–574

    CAS  PubMed  Google Scholar 

  • Sui WG, Lin H, Chen JJ et al (2012) Comprehensive analysis of transcription factor expression patterns in peripheral blood mononuclear cell of systemic lupus erythematosus. Int J Rheum Dis 15:212–219

    CAS  PubMed  Google Scholar 

  • Tajouri L, Fernandez F, Griffiths LR (2007) Gene expression studies in multiple sclerosis. Curr Genomics 8:181–189

    CAS  PubMed Central  PubMed  Google Scholar 

  • Tang X, Muniappan L, Tang G et al (2009a) Identification of glucose-regulated miRNAs from pancreatic {beta} cells reveals a role for miR-30d in insulin transcription. RNA 15:287–293

    Google Scholar 

  • Tang Y, Luo X, Cui H et al (2009b) MicroRNA-146A contributes to abnormal activation of the type I interferon pathway in human lupus by targeting the key signaling proteins. Arthritis Rheum 60:1065–1075

    Google Scholar 

  • Teruel R, Corral J, Pérez-Andreu V et al (2011) Potential role of miRNAs in developmental haemostasis. PLoS One 6:e17648

    CAS  PubMed Central  PubMed  Google Scholar 

  • Tisch R, Wang B (2008) Dysrulation of T cell peripheral tolerance in type 1 diabetes. Adv Immunol 100:125–149

    CAS  PubMed  Google Scholar 

  • Todd JA (2010) Etiology of type 1 diabetes. Immunity 32:457–467

    CAS  PubMed  Google Scholar 

  • Toukap AN, Galant C, Theate I et al (2007) Identification of distinct gene expression profiles in the synovium of patients with systemic lupus erythematosus. Arthritis Rheum 56:1579–1588

    CAS  Google Scholar 

  • Voulgarelis M, Giannouli S, Tasidou A et al (2006) Bone marrow histological findings in systemic lupus erythematosus with hematological abnormalities: a clinicopathological study. Am J Hematol 81:590–597

    CAS  PubMed  Google Scholar 

  • Vukkadapu SS, Belli JM, Ishii K et al (2005) Dynamic. interaction between T cell-mediated beta-cell damage and beta-cell repair in the. run up to autoimmune diabetes of the NOD mouse. Physiol Genomics 21:201–211

    CAS  PubMed  Google Scholar 

  • Wang G, Tam LS, Li EK et al (2010) Serum and urinary cell-free MiR-146a and MiR-155 in patients with systemic lupus erythematosus. J Rheumatol 37:2516–2522

    CAS  PubMed  Google Scholar 

  • Weckerle CE, Niewold TB (2011) The unexplained female predominance of systemic lupus erythematosus: clues from genetic and cytokine studies. Clin Rev Allergy Immunol 40:42–49

    CAS  PubMed Central  PubMed  Google Scholar 

  • Weckerle CE, Franek BS, Kelly JA et al (2011) Network analysis of associations between serum interferon-alpha activity, autoantibodies, and clinical features in systemic lupus erythematosus. Arthritis Rheum 63:1044–1053

    CAS  PubMed Central  PubMed  Google Scholar 

  • Weinshenker BG (1994) Natural history of multiple sclerosis. Ann Neurol 36:S6–S11

    PubMed  Google Scholar 

  • Wenzlau JM, Juhl K, Yu L et al (2007) The cation efflux transporter ZnT8 (Slc30A8) is a major autoantigen in human type 1 diabetes. Proc Natl Acad Sci U S A 104:17040–17045

    CAS  PubMed Central  PubMed  Google Scholar 

  • Willer CJ, Dyment DA, Risch NJ et al (2003) Twin concordance and sibling recurrence rates in multiple sclerosis. Proc Natl Acad Sci U S A 100:12877–12882

    CAS  PubMed Central  PubMed  Google Scholar 

  • Yao Y, Higgs BW, Morehouse C et al (2009) Development of potential pharmacodynamic and diagnostic markers for anti-IFN-α monoclonal antibody trials in systemic lupus erythematosus. Hum Genomics Proteomics pii: 374312

    Google Scholar 

  • Yuan Y, Kasar S, Underbayev C et al (2012) Role of microRNA-15a in autoantibody production in interferon-augmented murine model of lupus. Mol Immunol 52:61–70

    PubMed  Google Scholar 

  • Zhao X, Tang Y, Qu B et al (2010) MicroRNA-125a contributes to elevated inflammatory chemokine RANTES levels via targeting KLF13 in systemic lupus erythematosus. Arthritis Rheum 62:3425–3435

    CAS  PubMed  Google Scholar 

  • Zhao S, Wang Y, Liang Y et al (2011) MicroRNA-126 regulates DNA methylation in CD4+ T cells and contributes to systemic lupus erythematosus by targeting DNA methyl-transferase 1. Arthritis Rheum 63:1376–1386

    CAS  PubMed  Google Scholar 

  • Zhernakova A, van Diemen CC, Wijmenga C (2009) Detecting shared pathogenesis from the shared genetics of immune-related diseases. Nat Rev Genet 10:43–55

    CAS  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Medicine, Division of Clinical Immunology, Ribeirão Preto Medical School, University of São Paulo, 14049–900, Ribeirão Preto, SP, Brazil

    Cristhianna V. A. Collares & Eduardo A. Donadi

Authors
  1. Cristhianna V. A. Collares
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Eduardo A. Donadi
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Eduardo A. Donadi .

Editor information

Editors and Affiliations

  1. Department of Genetics, University of São Paulo, Ribeirão Preto, São Paulo, Brazil

    Geraldo A. Passos

Rights and permissions

Reprints and permissions

Copyright information

© 2014 Springer International Publishing Switzerland

About this chapter

Cite this chapter

Collares, C., Donadi, E. (2014). Transcriptome Profiling in Autoimmune Diseases. In: Passos, G. (eds) Transcriptomics in Health and Disease. Springer, Cham. https://doi.org/10.1007/978-3-319-11985-4_8

Download citation

Publish with us

Policies and ethics

Search

Navigation