1932

Abstract

Transcriptomics, the high-throughput characterization of RNAs, has been instrumental in defining pathogenic signatures in human autoimmunity and autoinflammation. It enabled the identification of new therapeutic targets in IFN-, IL-1- and IL-17-mediated diseases. Applied to immunomonitoring, transcriptomics is starting to unravel diagnostic and prognostic signatures that stratify patients, track molecular changes associated with disease activity, define personalized treatment strategies, and generally inform clinical practice. Herein, we review the use of transcriptomics to define mechanistic, diagnostic, and predictive signatures in human autoimmunity and autoinflammation. We discuss some of the analytical approaches applied to extract biological knowledge from high-dimensional data sets. Finally, we touch upon emerging applications of transcriptomics to study eQTLs, B and T cell repertoire diversity, and isoform usage.

Loading

Article metrics loading...

/content/journals/10.1146/annurev-immunol-051116-052225
2017-04-26
2024-06-23
Loading full text...

Full text loading...

/deliver/fulltext/immunol/35/1/annurev-immunol-051116-052225.html?itemId=/content/journals/10.1146/annurev-immunol-051116-052225&mimeType=html&fmt=ahah

Literature Cited

  1. Stoffels M, Kastner DL. 1.  2016. Old dogs, new tricks: monogenic autoinflammatory disease unleashed. Annu. Rev. Genom. Hum. Genet. 17:245–72 [Google Scholar]
  2. Arakawa A, Siewert K, Stohr J, Besgen P, Kim SM. 2.  et al. 2015. Melanocyte antigen triggers autoimmunity in human psoriasis. J. Exp. Med. 2122203–12 [Google Scholar]
  3. Maini RN, Brennan FM, Williams R, Chu CQ, Cope AP. 3.  et al. 1993. TNF-alpha in rheumatoid arthritis and prospects of anti-TNF therapy. Clin. Exp. Rheumatol. 11Suppl. 8S173–75 [Google Scholar]
  4. Elliott MJ, Maini RN, Feldmann M, Long-Fox A, Charles P. 4.  et al. 1993. Treatment of rheumatoid arthritis with chimeric monoclonal antibodies to tumor necrosis factor α. Arthritis Rheum. 361681–90 [Google Scholar]
  5. Dinarello CA. 5.  2014. An expanding role for interleukin-1 blockade from gout to cancer. Mol. Med. 20Suppl. 1S43–58 [Google Scholar]
  6. Papp KA, Leonardi C, Menter A, Ortonne JP, Krueger JG. 6.  et al. 2012. Brodalumab, an anti-interleukin-17-receptor antibody for psoriasis. N. Engl. J. Med. 3661181–89 [Google Scholar]
  7. Leonardi C, Matheson R, Zachariae C, Cameron G, Li L. 7.  et al. 2012. Anti-interleukin-17 monoclonal antibody ixekizumab in chronic plaque psoriasis. N. Engl. J. Med. 3661190–99 [Google Scholar]
  8. Langley RG, Elewski BE, Lebwohl M, Reich K, Griffiths CE. 8.  et al. 2014. Secukinumab in plaque psoriasis—results of two phase 3 trials. N. Engl. J. Med. 371326–38 [Google Scholar]
  9. Siebert S, Tsoukas A, Robertson J, McInnes I. 9.  2015. Cytokines as therapeutic targets in rheumatoid arthritis and other inflammatory diseases. Pharmacol. Rev. 67280–309 [Google Scholar]
  10. Kalunian KC, Merrill JT, Maciuca R, McBride JM, Townsend MJ. 10.  et al. 2016. A phase II study of the efficacy and safety of rontalizumab (rhuMAb interferon-alpha) in patients with systemic lupus erythematosus (ROSE). Ann. Rheum. Dis. 75196–202 [Google Scholar]
  11. Aguiar R, Araujo C, Martins-Coelho G, Isenberg D. 11.  2017. Use of rituximab in systemic lupus erythematosus: a single center experience over 14 years. Arthritis Care Res. 69257–62 [Google Scholar]
  12. Alizadeh A, Eisen M, Botstein D, Brown PO, Staudt LM. 12.  1998. Probing lymphocyte biology by genomic-scale gene expression analysis. J. Clin. Immunol. 18373–79 [Google Scholar]
  13. DeRisi J, Penland L, Brown PO, Bittner ML, Meltzer PS. 13.  et al. 1996. Use of a cDNA microarray to analyse gene expression patterns in human cancer. Nat. Genet. 14457–60 [Google Scholar]
  14. Golub TR, Slonim DK, Tamayo P, Huard C, Gaasenbeek M. 14.  et al. 1999. Molecular classification of cancer: Class discovery and class prediction by gene expression monitoring. Science 286531–37 [Google Scholar]
  15. Alizadeh AA, Eisen MB, Davis RE, Ma C, Lossos IS. 15.  et al. 2000. Distinct types of diffuse large B-cell lymphoma identified by gene expression profiling. Nature 403503–11 [Google Scholar]
  16. Sotiriou C, Pusztai L. 16.  2009. Gene-expression signatures in breast cancer. N. Engl. J. Med. 360790–800 [Google Scholar]
  17. 17. Cancer Genome Atlas Res. Netw 2011. Integrated genomic analyses of ovarian carcinoma. Nature 474609–15 [Google Scholar]
  18. 18. Cancer Genome Atlas Netw 2012. Comprehensive molecular portraits of human breast tumours. Nature 49061–70 [Google Scholar]
  19. Bennett L, Palucka AK, Arce E, Cantrell V, Borvak J. 19.  et al. 2003. Interferon and granulopoiesis signatures in systemic lupus erythematosus blood. J. Exp. Med. 197711–23 [Google Scholar]
  20. Baechler EC, Batliwalla FM, Karypis G, Gaffney PM, Ortmann WA. 20.  et al. 2003. Interferon-inducible gene expression signature in peripheral blood cells of patients with severe lupus. PNAS 100:2610–15 [Google Scholar]
  21. Berry MP, Graham CM, McNab FW, Xu Z, Bloch SA. 21.  et al. 2010. An interferon-inducible neutrophil-driven blood transcriptional signature in human tuberculosis. Nature 466973–77 [Google Scholar]
  22. Ramilo O, Allman W, Chung W, Mejias A, Ardura M. 22.  et al. 2007. Gene expression patterns in blood leukocytes discriminate patients with acute infections. Blood 1092066–77 [Google Scholar]
  23. Kane M, Yadav SS, Bitzegeio J, Kutluay SB, Zang T. 23.  et al. 2013. MX2 is an interferon-induced inhibitor of HIV-1 infection. Nature 502563–66 [Google Scholar]
  24. Calvano SE, Xiao W, Richards DR, Felciano RM, Baker HV. 24.  et al. 2005. A network-based analysis of systemic inflammation in humans. Nature 4371032–37 [Google Scholar]
  25. Boldrick JC, Alizadeh AA, Diehn M, Dudoit S, Liu CL. 25.  et al. 2002. Stereotyped and specific gene expression programs in human innate immune responses to bacteria. PNAS 99972–77 [Google Scholar]
  26. Zaas AK, Chen M, Varkey J, Veldman T, Hero AO. 26.  et al. 2009. Gene expression signatures diagnose influenza and other symptomatic respiratory viral infections in humans. Cell Host Microbe 6207–17 [Google Scholar]
  27. Obermoser G, Presnell S, Domico K, Xu H, Wang Y. 27.  et al. 2013. Systems scale interactive exploration reveals quantitative and qualitative differences in response to influenza and pneumococcal vaccines. Immunity 38831–44 [Google Scholar]
  28. Querec TD, Akondy RS, Lee EK, Cao W, Nakaya HI. 28.  et al. 2009. Systems biology approach predicts immunogenicity of the yellow fever vaccine in humans. Nat. Immunol. 10:116–25 [Google Scholar]
  29. Li S, Rouphael N, Duraisingham S, Romero-Steiner S, Presnell S. 29.  et al. 2014. Molecular signatures of antibody responses derived from a systems biology study of five human vaccines. Nat. Immunol. 15:195–204 [Google Scholar]
  30. Banchereau R, Baldwin N, Cepika AM, Athale S, Xue Y. 30.  et al. 2014. Transcriptional specialization of human dendritic cell subsets in response to microbial vaccines. Nat. Commun. 55283 [Google Scholar]
  31. Nakaya HI, Wrammert J, Lee EK, Racioppi L, Marie-Kunze S. 31.  et al. 2011. Systems biology of vaccination for seasonal influenza in humans. Nat. Immunol. 12:786–95 [Google Scholar]
  32. Tsang JS, Schwartzberg PL, Kotliarov Y, Biancotto A, Xie Z. 32.  et al. 2014. Global analyses of human immune variation reveal baseline predictors of postvaccination responses. Cell 157:499–513 [Google Scholar]
  33. Goodwin S, McPherson JD, McCombie WR. 33.  2016. Coming of age: ten years of next-generation sequencing technologies. Nat. Rev. Genet. 17:333–51 [Google Scholar]
  34. Cech TR, Steitz JA. 34.  2014. The noncoding RNA revolution—trashing old rules to forge new ones. Cell 157:77–94 [Google Scholar]
  35. Au KF, Sebastiano V, Afshar PT, Durruthy JD, Lee L. 35.  et al. 2013. Characterization of the human ESC transcriptome by hybrid sequencing. PNAS 110:E4821–30 [Google Scholar]
  36. Sharon D, Tilgner H, Grubert F, Snyder M. 36.  2013. A single-molecule long-read survey of the human transcriptome. Nat. Biotechnol. 311009–14 [Google Scholar]
  37. Buenrostro JD, Giresi PG, Zaba LC, Chang HY, Greenleaf WJ. 37.  2013. Transposition of native chromatin for fast and sensitive epigenomic profiling of open chromatin, DNA-binding proteins and nucleosome position. Nat. Methods 10:1213–18 [Google Scholar]
  38. Georgiou G, Ippolito GC, Beausang J, Busse CE, Wardemann H, Quake SR. 38.  2014. The promise and challenge of high-throughput sequencing of the antibody repertoire. Nat. Biotechnol. 32158–68 [Google Scholar]
  39. Woodsworth DJ, Castellarin M, Holt RA. 39.  2013. Sequence analysis of T-cell repertoires in health and disease. Genome Med. 598 [Google Scholar]
  40. Kolodziejczyk AA, Kim JK, Svensson V, Marioni JC, Teichmann SA. 40.  2015. The technology and biology of single-cell RNA sequencing. Mol. Cell 58610–20 [Google Scholar]
  41. Crow YJ. 41.  2011. Type I interferonopathies: a novel set of inborn errors of immunity. Ann. N. Y. Acad. Sci. 1238:91–98 [Google Scholar]
  42. Banchereau J, Pascual V. 42.  2006. Type I interferon in systemic lupus erythematosus and other autoimmune diseases. Immunity 25:383–92 [Google Scholar]
  43. Pascual V, Allantaz F, Arce E, Punaro M, Banchereau J. 43.  2005. Role of interleukin-1 (IL-1) in the pathogenesis of systemic onset juvenile idiopathic arthritis and clinical response to IL-1 blockade. J. Exp. Med. 201:1479–86 [Google Scholar]
  44. Noda S, Krueger JG, Guttman-Yassky E. 44.  2015. The translational revolution and use of biologics in patients with inflammatory skin diseases. J. Allergy Clin. Immunol. 135:324–36 [Google Scholar]
  45. Isaacs A, Lindenmann J. 45.  1957. Virus interference. I. The interferon. Proc. R. Soc. Lond. B Biol. Sci. 147:258–67 [Google Scholar]
  46. McNab F, Mayer-Barber K, Sher A, Wack A, O'Garra A. 46.  2015. Type I interferons in infectious disease. Nat. Rev. Immunol. 15:87–103 [Google Scholar]
  47. Schneider WM, Chevillotte MD, Rice CM. 47.  2014. Interferon-stimulated genes: a complex web of host defenses. Annu. Rev. Immunol. 32513–45 [Google Scholar]
  48. Stewart TA. 48.  2003. Neutralizing interferon alpha as a therapeutic approach to autoimmune diseases. Cytokine Growth Factor Rev. 14:139–54 [Google Scholar]
  49. Ivashkiv LB, Donlin LT. 49.  2014. Regulation of type I interferon responses. Nat. Rev. Immunol. 14:36–49 [Google Scholar]
  50. Jego G, Palucka AK, Blanck JP, Chalouni C, Pascual V, Banchereau J. 50.  2003. Plasmacytoid dendritic cells induce plasma cell differentiation through type I interferon and interleukin 6. Immunity 19:225–34 [Google Scholar]
  51. Joo H, Coquery C, Xue Y, Gayet I, Dillon SR. 51.  et al. 2012. Serum from patients with SLE instructs monocytes to promote IgG and IgA plasmablast differentiation. J. Exp. Med. 209:1335–48 [Google Scholar]
  52. Santini SM, Di Pucchio T, Lapenta C, Parlato S, Logozzi M, Belardelli F. 52.  2003. A new type I IFN-mediated pathway for the rapid differentiation of monocytes into highly active dendritic cells. Stem Cells 21:357–62 [Google Scholar]
  53. Le Bon A, Thompson C, Kamphuis E, Durand V, Rossmann C. 53.  et al. 2006. Cutting edge: enhancement of antibody responses through direct stimulation of B and T cells by type I IFN. J. Immunol. 176:2074–78 [Google Scholar]
  54. Cucak H, Yrlid U, Reizis B, Kalinke U, Johansson-Lindbom B. 54.  2009. Type I interferon signaling in dendritic cells stimulates the development of lymph-node-resident T follicular helper cells. Immunity 31491–501 [Google Scholar]
  55. Wack A, Terczynska-Dyla E, Hartmann R. 55.  2015. Guarding the frontiers: the biology of type III interferons. Nat. Immunol. 16:802–9 [Google Scholar]
  56. Medzhitov R. 56.  2007. Recognition of microorganisms and activation of the immune response. Nature 449819–26 [Google Scholar]
  57. Wu J, Chen ZJ. 57.  2014. Innate immune sensing and signaling of cytosolic nucleic acids. Annu. Rev. Immunol. 32461–88 [Google Scholar]
  58. Roers A, Hiller B, Hornung V. 58.  2016. Recognition of endogenous nucleic acids by the innate immune system. Immunity 44739–54 [Google Scholar]
  59. Ishikawa H, Ma Z, Barber GN. 59.  2009. STING regulates intracellular DNA-mediated, type I interferon-dependent innate immunity. Nature 461788–92 [Google Scholar]
  60. Xia P, Wang S, Ye B, Du Y, Huang G. 60.  et al. 2015. Sox2 functions as a sequence-specific DNA sensor in neutrophils to initiate innate immunity against microbial infection. Nat. Immunol. 16:366–75 [Google Scholar]
  61. Vallin H, Blomberg S, Alm GV, Cederblad B, Ronnblom L. 61.  1999. Patients with systemic lupus erythematosus (SLE) have a circulating inducer of interferon-alpha (IFN-α) production acting on leucocytes resembling immature dendritic cells. Clin. Exp. Immunol. 115:196–202 [Google Scholar]
  62. Means TK, Latz E, Hayashi F, Murali MR, Golenbock DT, Luster AD. 62.  2005. Human lupus autoantibody-DNA complexes activate DCs through cooperation of CD32 and TLR9. J. Clin. Investig. 115:407–17 [Google Scholar]
  63. Gilliet M, Cao W, Liu YJ. 63.  2008. Plasmacytoid dendritic cells: sensing nucleic acids in viral infection and autoimmune diseases. Nat. Rev. Immunol. 8594–606 [Google Scholar]
  64. Henault J, Martinez J, Riggs JM, Tian J, Mehta P. 64.  et al. 2012. Noncanonical autophagy is required for type I interferon secretion in response to DNA-immune complexes. Immunity 37986–97 [Google Scholar]
  65. Swiecki M, Colonna M. 65.  2015. The multifaceted biology of plasmacytoid dendritic cells. Nat. Rev. Immunol. 15:471–85 [Google Scholar]
  66. Rusinova I, Forster S, Yu S, Kannan A, Masse M. 66.  et al. 2013. Interferome v2.0: an updated database of annotated interferon-regulated genes. Nucleic Acids Res. 41D1040–46 [Google Scholar]
  67. Hall JC, Casciola-Rosen L, Berger AE, Kapsogeorgou EK, Cheadle C. 67.  et al. 2012. Precise probes of type II interferon activity define the origin of interferon signatures in target tissues in rheumatic diseases. PNAS 109:17609–14 [Google Scholar]
  68. Negishi H, Osawa T, Ogami K, Ouyang X, Sakaguchi S. 68.  et al. 2008. A critical link between Toll-like receptor 3 and type II interferon signaling pathways in antiviral innate immunity. PNAS 105:20446–51 [Google Scholar]
  69. Chaussabel D, Baldwin N. 69.  2014. Democratizing systems immunology with modular transcriptional repertoire analyses. Nat. Rev. Immunol. 14:271–80 [Google Scholar]
  70. Pascual V, Chaussabel D, Banchereau J. 70.  2010. A genomic approach to human autoimmune diseases. Annu. Rev. Immunol. 28:535–71 [Google Scholar]
  71. Suarez NM, Bunsow E, Falsey AR, Walsh EE, Mejias A, Ramilo O. 71.  2015. Superiority of transcriptional profiling over procalcitonin for distinguishing bacterial from viral lower respiratory tract infections in hospitalized adults. J. Infect. Dis. 212:213–22 [Google Scholar]
  72. Banchereau R, Hong S, Cantarel B, Baldwin N, Baisch J. 72.  et al. 2016. Personalized immunomonitoring uncovers molecular networks that stratify lupus patients. Cell 165:551–65 [Google Scholar]
  73. Mostafavi S, Yoshida H, Moodley D, LeBoite H, Rothamel K. 73.  et al. 2016. Parsing the interferon transcriptional network and its disease associations. Cell 164:564–78 [Google Scholar]
  74. Crow YJ, Manel N. 74.  2015. Aicardi-Goutières syndrome and the type I interferonopathies. Nat. Rev. Immunol. 15:429–40 [Google Scholar]
  75. Hooks JJ, Moutsopoulos HM, Geis SA, Stahl NI, Decker JL, Notkins AL. 75.  1979. Immune interferon in the circulation of patients with autoimmune disease. N. Engl. J. Med. 3015–8 [Google Scholar]
  76. Preble OT, Black RJ, Friedman RM, Klippel JH, Vilcek J. 76.  1982. Systemic lupus erythematosus: presence in human serum of an unusual acid-labile leukocyte interferon. Science 216:429–31 [Google Scholar]
  77. Blanco P, Palucka AK, Gill M, Pascual V, Banchereau J. 77.  2001. Induction of dendritic cell differentiation by IFN-alpha in systemic lupus erythematosus. Science 294:1540–43 [Google Scholar]
  78. Chiche L, Jourde-Chiche N, Whalen E, Presnell S, Gersuk V. 78.  et al. 2014. Modular transcriptional repertoire analyses of adults with systemic lupus erythematosus reveal distinct type I and type II interferon signatures. Arthritis Rheumatol. 661583–95 [Google Scholar]
  79. Chaussabel D, Quinn C, Shen J, Patel P, Glaser C. 79.  et al. 2008. A modular analysis framework for blood genomics studies: application to systemic lupus erythematosus. Immunity 29:150–64 [Google Scholar]
  80. Petri M, Singh S, Tesfasyone H, Dedrick R, Fry K. 80.  et al. 2009. Longitudinal expression of type I interferon responsive genes in systemic lupus erythematosus. Lupus 18:980–89 [Google Scholar]
  81. Kirou KA, Lee C, George S, Louca K, Peterson MG, Crow MK. 81.  2005. Activation of the interferon-α pathway identifies a subgroup of systemic lupus erythematosus patients with distinct serologic features and active disease. Arthritis Rheum. 521491–503 [Google Scholar]
  82. Guiducci C, Gong M, Xu Z, Gill M, Chaussabel D. 82.  et al. 2010. TLR recognition of self nucleic acids hampers glucocorticoid activity in lupus. Nature 465937–41 [Google Scholar]
  83. Yokoyama H, Takabatake T, Takaeda M, Wada T, Naito T. 83.  et al. 1992. Up-regulated MHC-class II expression and gamma-IFN and soluble IL-2R in lupus nephritis. Kidney Int. 42755–63 [Google Scholar]
  84. Haas C, Ryffel B, Le Hir M. 84.  1997. IFN-gamma is essential for the development of autoimmune glomerulonephritis in MRL/Ipr mice. J. Immunol. 158:5484–91 [Google Scholar]
  85. Oon S, Wilson NJ, Wicks I. 85.  2016. Targeted therapeutics in SLE: emerging strategies to modulate the interferon pathway. Clin. Transl. Immunol. 5e79 [Google Scholar]
  86. Higgs BW, Liu Z, White B, Zhu W, White WI. 86.  et al. 2011. Patients with systemic lupus erythematosus, myositis, rheumatoid arthritis and scleroderma share activation of a common type I interferon pathway. Ann. Rheum. Dis. 702029–36 [Google Scholar]
  87. An J, Briggs TA, Dumax-Vorzet A, Alarcon-Riquelme ME, Belot A. 87.  et al. 2017. Tartrate-resistant acid phosphatase deficiency in the predisposition to systemic lupus erythematosus. Arthritis Rheumatol. 69131–42 [Google Scholar]
  88. Santer DM, Hall BE, George TC, Tangsombatvisit S, Liu CL. 88.  et al. 2010. C1q deficiency leads to the defective suppression of IFN-alpha in response to nucleoprotein containing immune complexes. J. Immunol. 185:4738–49 [Google Scholar]
  89. Lauwerys BR, Hachulla E, Spertini F, Lazaro E, Jorgensen C. 89.  et al. 2013. Down-regulation of interferon signature in systemic lupus erythematosus patients by active immunization with interferon alpha-kinoid. Arthritis Rheum. 65447–56 [Google Scholar]
  90. Emamian ES, Leon JM, Lessard CJ, Grandits M, Baechler EC. 90.  et al. 2009. Peripheral blood gene expression profiling in Sjögren's syndrome. Genes Immun. 10:285–96 [Google Scholar]
  91. Hjelmervik TO, Petersen K, Jonassen I, Jonsson R, Bolstad AI. 91.  2005. Gene expression profiling of minor salivary glands clearly distinguishes primary Sjögren's syndrome patients from healthy control subjects. Arthritis Rheum. 521534–44 [Google Scholar]
  92. Greenberg SA. 92.  2010. Type 1 interferons and myositis. Arthritis Res. Ther. 12Suppl. 1S4 [Google Scholar]
  93. Baechler EC, Bauer JW, Slattery CA, Ortmann WA, Espe KJ. 93.  et al. 2007. An interferon signature in the peripheral blood of dermatomyositis patients is associated with disease activity. Mol. Med. 13:59–68 [Google Scholar]
  94. Walsh RJ, Kong SW, Yao Y, Jallal B, Kiener PA. 94.  et al. 2007. Type I interferon-inducible gene expression in blood is present and reflects disease activity in dermatomyositis and polymyositis. Arthritis Rheum. 563784–92 [Google Scholar]
  95. Wong D, Kea B, Pesich R, Higgs BW, Zhu W. 95.  et al. 2012. Interferon and biologic signatures in dermatomyositis skin: specificity and heterogeneity across diseases. PLOS ONE 7e29161 [Google Scholar]
  96. van der Pouw Kraan TC, Wijbrandts CA, van Baarsen LG, Voskuyl AE, Rustenburg F. 96.  et al. 2007. Rheumatoid arthritis subtypes identified by genomic profiling of peripheral blood cells: assignment of a type I interferon signature in a subpopulation of patients. Ann. Rheum. Dis. 661008–14 [Google Scholar]
  97. Reynier F, Petit F, Paye M, Turrel-Davin F, Imbert PE. 97.  et al. 2011. Importance of correlation between gene expression levels: application to the type I interferon signature in rheumatoid arthritis. PLOS ONE 6e24828 [Google Scholar]
  98. Sekiguchi N, Kawauchi S, Furuya T, Inaba N, Matsuda K. 98.  et al. 2008. Messenger ribonucleic acid expression profile in peripheral blood cells from RA patients following treatment with an anti-TNF-α monoclonal antibody, infliximab. Rheumatology 47780–88 [Google Scholar]
  99. Bowcock AM, Shannon W, Du F, Duncan J, Cao K. 99.  et al. 2001. Insights into psoriasis and other inflammatory diseases from large-scale gene expression studies. Hum. Mol. Genet. 10:1793–805 [Google Scholar]
  100. Nestle FO, Conrad C, Tun-Kyi A, Homey B, Gombert M. 100.  et al. 2005. Plasmacytoid predendritic cells initiate psoriasis through interferon-alpha production. J. Exp. Med. 202:135–43 [Google Scholar]
  101. Tan FK, Zhou X, Mayes MD, Gourh P, Guo X. 101.  et al. 2006. Signatures of differentially regulated interferon gene expression and vasculotrophism in the peripheral blood cells of systemic sclerosis patients. Rheumatology 45694–702 [Google Scholar]
  102. Bos CL, van Baarsen LG, Timmer TC, Overbeek MJ, Basoski NM. 102.  et al. 2009. Molecular subtypes of systemic sclerosis in association with anti-centromere antibodies and digital ulcers. Genes Immun. 10:210–18 [Google Scholar]
  103. Brkic Z, van Bon L, Cossu M, van Helden-Meeuwsen CG, Vonk MC. 103.  et al. 2016. The interferon type I signature is present in systemic sclerosis before overt fibrosis and might contribute to its pathogenesis through high BAFF gene expression and high collagen synthesis. Ann. Rheum. Dis. 751567–73 [Google Scholar]
  104. Ferreira RC, Guo H, Coulson RM, Smyth DJ, Pekalski ML. 104.  et al. 2014. A type I interferon transcriptional signature precedes autoimmunity in children genetically at risk for type 1 diabetes. Diabetes 632538–50 [Google Scholar]
  105. Arbore G, West EE, Spolski R, Robertson AA, Klos A. 105.  et al. 2016. T helper 1 immunity requires complement-driven NLRP3 inflammasome activity in CD4+ T cells. Science 352:aad1210 [Google Scholar]
  106. Garlanda C, Dinarello CA, Mantovani A. 106.  2013. The interleukin-1 family: back to the future. Immunity 391003–18 [Google Scholar]
  107. Sharma D, Kanneganti TD. 107.  2016. The cell biology of inflammasomes: mechanisms of inflammasome activation and regulation. J. Cell Biol. 213:617–29 [Google Scholar]
  108. Jesus AA, Goldbach-Mansky R. 108.  2014. IL-1 blockade in autoinflammatory syndromes. Annu. Rev. Med. 65223–44 [Google Scholar]
  109. Moghaddas F, Masters SL. 109.  2015. Monogenic autoinflammatory diseases: cytokinopathies. Cytokine 74237–46 [Google Scholar]
  110. Cavalli G, Dinarello CA. 110.  2015. Treating rheumatological diseases and co-morbidities with interleukin-1 blocking therapies. Rheumatology 542134–44 [Google Scholar]
  111. Alsina L, Israelsson E, Altman MC, Dang KK, Ghandil P. 111.  et al. 2014. A narrow repertoire of transcriptional modules responsive to pyogenic bacteria is impaired in patients carrying loss-of-function mutations in MYD88 or IRAK4. Nat. Immunol. 15:1134–42 [Google Scholar]
  112. Bruck N, Schnabel A, Hedrich CM. 112.  2015. Current understanding of the pathophysiology of systemic juvenile idiopathic arthritis (sJIA) and target-directed therapeutic approaches. Clin. Immunol. 159:72–83 [Google Scholar]
  113. Allantaz F, Chaussabel D, Stichweh D, Bennett L, Allman W. 113.  et al. 2007. Blood leukocyte microarrays to diagnose systemic onset juvenile idiopathic arthritis and follow the response to IL-1 blockade. J. Exp. Med. 204:2131–44 [Google Scholar]
  114. Fall N, Barnes M, Thornton S, Luyrink L, Olson J. 114.  et al. 2007. Gene expression profiling of peripheral blood from patients with untreated new-onset systemic juvenile idiopathic arthritis reveals molecular heterogeneity that may predict macrophage activation syndrome. Arthritis Rheum. 563793–804 [Google Scholar]
  115. Quartier P, Allantaz F, Cimaz R, Pillet P, Messiaen C. 115.  et al. 2011. A multicentre, randomised, double-blind, placebo-controlled trial with the interleukin-1 receptor antagonist anakinra in patients with systemic-onset juvenile idiopathic arthritis (ANAJIS trial). Ann. Rheum. Dis. 70747–54 [Google Scholar]
  116. Ruperto N, Brunner HI, Quartier P, Constantin T, Wulffraat N. 116.  et al. 2012. Two randomized trials of canakinumab in systemic juvenile idiopathic arthritis. N. Engl. J. Med. 3672396–406 [Google Scholar]
  117. Ilowite NT, Prather K, Lokhnygina Y, Schanberg LE, Elder M. 117.  et al. 2014. Randomized, double-blind, placebo-controlled trial of the efficacy and safety of rilonacept in the treatment of systemic juvenile idiopathic arthritis. Arthritis Rheumatol. 662570–79 [Google Scholar]
  118. De Benedetti F, Brunner HI, Ruperto N, Kenwright A, Wright S. 118.  et al. 2012. Randomized trial of tocilizumab in systemic juvenile idiopathic arthritis. N. Engl. J. Med. 3672385–95 [Google Scholar]
  119. Canna SW, de Jesus AA, Gouni S, Brooks SR, Marrero B. 119.  et al. 2014. An activating NLRC4 inflammasome mutation causes autoinflammation with recurrent macrophage activation syndrome. Nat. Genet. 461140–46 [Google Scholar]
  120. Balow JE Jr., Ryan JG, Chae JJ, Booty MG, Bulua A. 120.  et al. 2013. Microarray-based gene expression profiling in patients with cryopyrin-associated periodic syndromes defines a disease-related signature and IL-1-responsive transcripts. Ann. Rheum. Dis. 721064–70 [Google Scholar]
  121. Hoang LT, Shimizu C, Ling L, Naim AN, Khor CC. 121.  et al. 2014. Global gene expression profiling identifies new therapeutic targets in acute Kawasaki disease. Genome Med. 6541 [Google Scholar]
  122. Popper SJ, Shimizu C, Shike H, Kanegaye JT, Newburger JW. 122.  et al. 2007. Gene-expression patterns reveal underlying biological processes in Kawasaki disease. Genome Biol. 8R261 [Google Scholar]
  123. Fury W, Tremoulet AH, Watson VE, Best BM, Shimizu C. 123.  et al. 2010. Transcript abundance patterns in Kawasaki disease patients with intravenous immunoglobulin resistance. Hum. Immunol. 71865–73 [Google Scholar]
  124. Kaizer EC, Glaser CL, Chaussabel D, Banchereau J, Pascual V, White PC. 124.  2007. Gene expression in peripheral blood mononuclear cells from children with diabetes. J. Clin. Endocrinol. Metab. 923705–11 [Google Scholar]
  125. Wang X, Jia S, Geoffrey R, Alemzadeh R, Ghosh S, Hessner MJ. 125.  2008. Identification of a molecular signature in human type 1 diabetes mellitus using serum and functional genomics. J. Immunol. 180:1929–37 [Google Scholar]
  126. Moran A, Bundy B, Becker DJ, DiMeglio LA, Gitelman SE. 126.  et al. 2013. Interleukin-1 antagonism in type 1 diabetes of recent onset: Two multicentre, randomised, double-blind, placebo-controlled trials. Lancet 3811905–15 [Google Scholar]
  127. Leonardi CL, Kimball AB, Papp KA, Yeilding N, Guzzo C. 127.  et al. 2008. 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). Lancet 3711665–74 [Google Scholar]
  128. Lee E, Trepicchio WL, Oestreicher JL, Pittman D, Wang F. 128.  et al. 2004. Increased expression of interleukin 23 p19 and p40 in lesional skin of patients with psoriasis vulgaris. J. Exp. Med. 199:125–30 [Google Scholar]
  129. Zheng Y, Danilenko DM, Valdez P, Kasman I, Eastham-Anderson J. 129.  et al. 2007. Interleukin-22, a TH17 cytokine, mediates IL-23-induced dermal inflammation and acanthosis. Nature 445648–51 [Google Scholar]
  130. Russell CB, Rand H, Bigler J, Kerkof K, Timour M. 130.  et al. 2014. Gene expression profiles normalized in psoriatic skin by treatment with brodalumab, a human anti-IL-17 receptor monoclonal antibody. J. Immunol. 192:3828–36 [Google Scholar]
  131. Zaba LC, Suarez-Farinas M, Fuentes-Duculan J, Nograles KE, Guttman-Yassky E. 131.  et al. 2009. Effective treatment of psoriasis with etanercept is linked to suppression of IL-17 signaling, not immediate response TNF genes. J. Allergy Clin. Immunol. 124:1022–30.e395 [Google Scholar]
  132. Jordan CT, Cao L, Roberson ED, Pierson KC, Yang CF. 132.  et al. 2012. PSORS2 is due to mutations in CARD14. Am. J. Hum. Genet. 90784–95 [Google Scholar]
  133. Marrakchi S, Guigue P, Renshaw BR, Puel A, Pei XY. 133.  et al. 2011. Interleukin-36-receptor antagonist deficiency and generalized pustular psoriasis. N. Engl. J. Med. 365620–28 [Google Scholar]
  134. Berki DM, Liu L, Choon SE, Burden AD, Griffiths CE. 134.  et al. 2015. Activating CARD14 mutations are associated with generalized pustular psoriasis but rarely account for familial recurrence in psoriasis vulgaris. J. Investig. Dermatol. 135:2964–70 [Google Scholar]
  135. Tozzoli R. 135.  2007. Recent advances in diagnostic technologies and their impact in autoimmune diseases. Autoimmun. Rev. 6334–40 [Google Scholar]
  136. Fritzler MJ. 136.  2006. Advances and applications of multiplexed diagnostic technologies in autoimmune diseases. Lupus 15:422–27 [Google Scholar]
  137. Costello CM, Mah N, Hasler R, Rosenstiel P, Waetzig GH. 137.  et al. 2005. Dissection of the inflammatory bowel disease transcriptome using genome-wide cDNA microarrays. PLOS Med. 2e199 [Google Scholar]
  138. Burczynski ME, Peterson RL, Twine NC, Zuberek KA, Brodeur BJ. 138.  et al. 2006. Molecular classification of Crohn's disease and ulcerative colitis patients using transcriptional profiles in peripheral blood mononuclear cells. J. Mol. Diagn. 851–61 [Google Scholar]
  139. Ungethuem U, Haeupl T, Witt H, Koczan D, Krenn V. 139.  et al. 2010. Molecular signatures and new candidates to target the pathogenesis of rheumatoid arthritis. Physiol. Genom. 42A267–82 [Google Scholar]
  140. Tuller T, Atar S, Ruppin E, Gurevich M, Achiron A. 140.  2013. Common and specific signatures of gene expression and protein-protein interactions in autoimmune diseases. Genes Immun. 14:67–82 [Google Scholar]
  141. Liu H, Liu J, Toups M, Soos T, Arendt C. 141.  2016. Gene signature-based mapping of immunological systems and diseases. BMC Bioinform. 17171 [Google Scholar]
  142. Levy H, Wang X, Kaldunski M, Jia S, Kramer J. 142.  et al. 2012. Transcriptional signatures as a disease-specific and predictive inflammatory biomarker for type 1 diabetes. Genes Immun. 13:593–604 [Google Scholar]
  143. Arbuckle MR, McClain MT, Rubertone MV, Scofield RH, Dennis GJ. 143.  et al. 2003. Development of autoantibodies before the clinical onset of systemic lupus erythematosus. N. Engl. J. Med. 3491526–33 [Google Scholar]
  144. Rodriguez-Calvo T, von Herrath MG. 144.  2015. Enterovirus infection and type 1 diabetes: closing in on a link?. Diabetes 641503–5 [Google Scholar]
  145. Stene LC, Oikarinen S, Hyoty H, Barriga KJ, Norris JM. 145.  et al. 2010. Enterovirus infection and progression from islet autoimmunity to type 1 diabetes: the Diabetes and Autoimmunity Study in the Young (DAISY). Diabetes 593174–80 [Google Scholar]
  146. Hummel S, Pfluger M, Hummel M, Bonifacio E, Ziegler AG. 146.  2011. Primary dietary intervention study to reduce the risk of islet autoimmunity in children at increased risk for type 1 diabetes: the BABYDIET study. Diabetes Care 341301–5 [Google Scholar]
  147. Jin Y, Sharma A, Bai S, Davis C, Liu H. 147.  et al. 2014. Risk of type 1 diabetes progression in islet autoantibody-positive children can be further stratified using expression patterns of multiple genes implicated in peripheral blood lymphocyte activation and function. Diabetes 632506–15 [Google Scholar]
  148. Kallionpaa H, Elo LL, Laajala E, Mykkanen J, Ricano-Ponce I. 148.  et al. 2014. Innate immune activity is detected prior to seroconversion in children with HLA-conferred type 1 diabetes susceptibility. Diabetes 632402–14 [Google Scholar]
  149. Meyer S, Woodward M, Hertel C, Vlaicu P, Haque Y. 149.  et al. 2016. AIRE-deficient patients harbor unique high-affinity disease-ameliorating autoantibodies. Cell 166:582–95 [Google Scholar]
  150. McKinney EF, Lyons PA, Carr EJ, Hollis JL, Jayne DR. 150.  et al. 2010. A CD8+ T cell transcription signature predicts prognosis in autoimmune disease. Nat. Med. 16:586–91 [Google Scholar]
  151. Lee JC, Lyons PA, McKinney EF, Sowerby JM, Carr EJ. 151.  et al. 2011. Gene expression profiling of CD8+ T cells predicts prognosis in patients with Crohn disease and ulcerative colitis. J. Clin. Investig. 121:4170–79 [Google Scholar]
  152. McKinney EF, Lee JC, Jayne DR, Lyons PA, Smith KG. 152.  2015. T-cell exhaustion, co-stimulation and clinical outcome in autoimmunity and infection. Nature 523:612–16 [Google Scholar]
  153. Caielli S, Athale S, Domic B, Murat E, Chandra M. 153.  et al. 2016. Oxidized mitochondrial nucleoids released by neutrophils drive type I interferon production in human lupus. J. Exp. Med. 213:697–713 [Google Scholar]
  154. Peterson KS, Huang JF, Zhu J, D'Agati V, Liu X. 154.  et al. 2004. Characterization of heterogeneity in the molecular pathogenesis of lupus nephritis from transcriptional profiles of laser-captured glomeruli. J. Clin. Investig. 113:1722–33 [Google Scholar]
  155. Sackmann EK, Fulton AL, Beebe DJ. 155.  2014. The present and future role of microfluidics in biomedical research. Nature 507181–89 [Google Scholar]
  156. Rubbert-Roth A, Finckh A. 156.  2009. Treatment options in patients with rheumatoid arthritis failing initial TNF inhibitor therapy: a critical review. Arthritis Res. Ther. 11:(Suppl.)1S1 [Google Scholar]
  157. Roda G, Jharap B, Neeraj N, Colombel JF. 157.  2016. Loss of response to anti-TNFs: definition, epidemiology, and management. Clin. Transl. Gastroenterol. 7e135 [Google Scholar]
  158. Merrill JT, Neuwelt CM, Wallace DJ, Shanahan JC, Latinis KM. 158.  et al. 2010. Efficacy and safety of rituximab in moderately-to-severely active systemic lupus erythematosus: The randomized, double-blind, phase II/III systemic lupus erythematosus evaluation of rituximab trial. Arthritis Rheum. 62222–33 [Google Scholar]
  159. Nirmala N, Brachat A, Feist E, Blank N, Specker C. 159.  et al. 2015. Gene-expression analysis of adult-onset Still's disease and systemic juvenile idiopathic arthritis is consistent with a continuum of a single disease entity. Pediatr. Rheumatol. Online J. 1350 [Google Scholar]
  160. Goldbach-Mansky R, Dailey NJ, Canna SW, Gelabert A, Jones J. 160.  et al. 2006. Neonatal-onset multisystem inflammatory disease responsive to interleukin-1β inhibition. N. Engl. J. Med. 355581–92 [Google Scholar]
  161. Simonini G, Xu Z, Caputo R, De Libero C, Pagnini I. 161.  et al. 2013. Clinical and transcriptional response to the long-acting interleukin-1 blocker canakinumab in Blau syndrome-related uveitis. Arthritis Rheum. 65513–18 [Google Scholar]
  162. Yao Y, Richman L, Higgs BW, Morehouse CA, de los Reyes M. 162.  et al. 2009. Neutralization of interferon-α/β-inducible genes and downstream effect in a phase I trial of an anti-interferon-α monoclonal antibody in systemic lupus erythematosus. Arthritis Rheum. 601785–96 [Google Scholar]
  163. Merrill JT, Wallace DJ, Petri M, Kirou KA, Yao Y. 163.  et al. 2011. Safety profile and clinical activity of sifalimumab, a fully human anti-interferon alpha monoclonal antibody, in systemic lupus erythematosus: a phase I, multicentre, double-blind randomised study. Ann. Rheum. Dis. 701905–13 [Google Scholar]
  164. Petri M, Wallace DJ, Spindler A, Chindalore V, Kalunian K. 164.  et al. 2013. Sifalimumab, a human anti-interferon-alpha monoclonal antibody, in systemic lupus erythematosus: a phase I randomized, controlled, dose-escalation study. Arthritis Rheum. 651011–21 [Google Scholar]
  165. McBride JM, Jiang J, Abbas AR, Morimoto A, Li J. 165.  et al. 2012. Safety and pharmacodynamics of rontalizumab in patients with systemic lupus erythematosus: results of a phase I, placebo-controlled, double-blind, dose-escalation study. Arthritis Rheum. 643666–76 [Google Scholar]
  166. Wang B, Higgs BW, Chang L, Vainshtein I, Liu Z. 166.  et al. 2013. Pharmacogenomics and translational simulations to bridge indications for an anti-interferon-alpha receptor antibody. Clin. Pharmacol. Ther. 93483–92 [Google Scholar]
  167. Chung L, Fiorentino DF, Benbarak MJ, Adler AS, Mariano MM. 167.  et al. 2009. Molecular framework for response to imatinib mesylate in systemic sclerosis. Arthritis Rheum. 60584–91 [Google Scholar]
  168. Johnston A, Guzman AM, Swindell WR, Wang F, Kang S, Gudjonsson JE. 168.  2014. Early tissue responses in psoriasis to the antitumour necrosis factor-alpha biologic etanercept suggest reduced interleukin-17 receptor expression and signalling. Br. J. Dermatol. 171:97–107 [Google Scholar]
  169. Sofen H, Smith S, Matheson RT, Leonardi CL, Calderon C. 169.  et al. 2014. Guselkumab (an IL-23-specific mAb) demonstrates clinical and molecular response in patients with moderate-to-severe psoriasis. J. Allergy Clin. Immunol. 133:1032–40 [Google Scholar]
  170. Ogihara Y, Ogata S, Nomoto K, Ebato T, Sato K. 170.  et al. 2014. Transcriptional regulation by infliximab therapy in Kawasaki disease patients with immunoglobulin resistance. Pediatr. Res. 76287–93 [Google Scholar]
  171. Serrano-Fernandez P, Moller S, Goertsches R, Fiedler H, Koczan D. 171.  et al. 2010. Time course transcriptomics of IFNB1b drug therapy in multiple sclerosis. Autoimmunity 43172–78 [Google Scholar]
  172. Sturzebecher S, Wandinger KP, Rosenwald A, Sathyamoorthy M, Tzou A. 172.  et al. 2003. Expression profiling identifies responder and non-responder phenotypes to interferon-beta in multiple sclerosis. Brain 126:1419–29 [Google Scholar]
  173. Guarda G, Braun M, Staehli F, Tardivel A, Mattmann C. 173.  et al. 2011. Type I interferon inhibits interleukin-1 production and inflammasome activation. Immunity 34213–23 [Google Scholar]
  174. Palucka AK, Blanck JP, Bennett L, Pascual V, Banchereau J. 174.  2005. Cross-regulation of TNF and IFN-alpha in autoimmune diseases. PNAS 102:3372–77 [Google Scholar]
  175. Burska AN, Roget K, Blits M, Soto Gomez L, van de Loo F. 175.  et al. 2014. Gene expression analysis in RA: towards personalized medicine. Pharmacogenomics J. 14:93–106 [Google Scholar]
  176. Lequerre T, Gauthier-Jauneau AC, Bansard C, Derambure C, Hiron M. 176.  et al. 2006. Gene profiling in white blood cells predicts infliximab responsiveness in rheumatoid arthritis. Arthritis Res. Ther. 8R105 [Google Scholar]
  177. Oliveira RD, Fontana V, Junta CM, Marques MM, Macedo C. 177.  et al. 2012. Differential gene expression profiles may differentiate responder and nonresponder patients with rheumatoid arthritis for methotrexate (MTX) monotherapy and MTX plus tumor necrosis factor inhibitor combined therapy. J. Rheumatol. 39:1524–32 [Google Scholar]
  178. Dennis G Jr., Holweg CT, Kummerfeld SK, Choy DF, Setiadi AF. 178.  et al. 2014. Synovial phenotypes in rheumatoid arthritis correlate with response to biologic therapeutics. Arthritis Res. Ther. 16R90 [Google Scholar]
  179. Wright HL, Thomas HB, Moots RJ, Edwards SW. 179.  2015. Interferon gene expression signature in rheumatoid arthritis neutrophils correlates with a good response to TNFi therapy. Rheumatology 54188–93 [Google Scholar]
  180. Sanayama Y, Ikeda K, Saito Y, Kagami S, Yamagata M. 180.  et al. 2014. Prediction of therapeutic responses to tocilizumab in patients with rheumatoid arthritis: biomarkers identified by analysis of gene expression in peripheral blood mononuclear cells using genome-wide DNA microarray. Arthritis Rheumatol. 661421–31 [Google Scholar]
  181. van Baarsen LG, Wijbrandts CA, Rustenburg F, Cantaert T, van der Pouw Kraan TC. 181.  et al. 2010. Regulation of IFN response gene activity during infliximab treatment in rheumatoid arthritis is associated with clinical response to treatment. Arthritis Res. Ther. 12R11 [Google Scholar]
  182. Koczan D, Drynda S, Hecker M, Drynda A, Guthke R. 182.  et al. 2008. Molecular discrimination of responders and nonresponders to anti-TNF alpha therapy in rheumatoid arthritis by etanercept. Arthritis Res. Ther. 10R50 [Google Scholar]
  183. Thurlings RM, Boumans M, Tekstra J, van Roon JA, Vos K. 183.  et al. 2010. Relationship between the type I interferon signature and the response to rituximab in rheumatoid arthritis patients. Arthritis Rheum. 623607–14 [Google Scholar]
  184. Raterman HG, Vosslamber S, de Ridder S, Nurmohamed MT, Lems WF. 184.  et al. 2012. The interferon type I signature towards prediction of non-response to rituximab in rheumatoid arthritis patients. Arthritis Res. Ther. 14R95 [Google Scholar]
  185. Sellam J, Marion-Thore S, Dumont F, Jacques S, Garchon HJ. 185.  et al. 2014. Use of whole-blood transcriptomic profiling to highlight several pathophysiologic pathways associated with response to rituximab in patients with rheumatoid arthritis: data from a randomized, controlled, open-label trial. Arthritis Rheumatol. 662015–25 [Google Scholar]
  186. Owczarczyk K, Lal P, Abbas AR, Wolslegel K, Holweg CT. 186.  et al. 2011. A plasmablast biomarker for nonresponse to antibody therapy to CD20 in rheumatoid arthritis. Sci. Transl. Med. 3101ra92 [Google Scholar]
  187. Kiefer K, Oropallo MA, Cancro MP, Marshak-Rothstein A. 187.  2012. Role of type I interferons in the activation of autoreactive B cells. Immunol. Cell Biol. 90498–504 [Google Scholar]
  188. Jourde-Chiche N, Chiche L, Chaussabel D. 188.  2016. Introducing a new dimension to molecular disease classifications. Trends Mol. Med. 22:451–53 [Google Scholar]
  189. Rosenblum MD, Remedios KA, Abbas AK. 189.  2015. Mechanisms of human autoimmunity. J. Clin. Investig. 125:2228–33 [Google Scholar]
  190. Calis JJ, Rosenberg BR. 190.  2014. Characterizing immune repertoires by high throughput sequencing: strategies and applications. Trends Immunol. 35581–90 [Google Scholar]
  191. Robinson WH. 191.  2015. Sequencing the functional antibody repertoire–diagnostic and therapeutic discovery. Nat. Rev. Rheumatol. 11:171–82 [Google Scholar]
  192. Tipton CM, Fucile CF, Darce J, Chida A, Ichikawa T. 192.  et al. 2015. Diversity, cellular origin and autoreactivity of antibody-secreting cell population expansions in acute systemic lupus erythematosus. Nat. Immunol. 16:755–65 [Google Scholar]
  193. Stern JN, Yaari G, Vander Heiden JA, Church G, Donahue WF. 193.  et al. 2014. B cells populating the multiple sclerosis brain mature in the draining cervical lymph nodes. Sci. Transl. Med. 6248ra107 [Google Scholar]
  194. Planas R, Jelcic I, Schippling S, Martin R, Sospedra M. 194.  2012. Natalizumab treatment perturbs memory- and marginal zone-like B-cell homing in secondary lymphoid organs in multiple sclerosis. Eur. J. Immunol. 42:790–98 [Google Scholar]
  195. Tan YC, Kongpachith S, Blum LK, Ju CH, Lahey LJ. 195.  et al. 2014. Barcode-enabled sequencing of plasmablast antibody repertoires in rheumatoid arthritis. Arthritis Rheumatol. 662706–15 [Google Scholar]
  196. Doorenspleet ME, Klarenbeek PL, de Hair MJ, van Schaik BD, Esveldt RE. 196.  et al. 2014. Rheumatoid arthritis synovial tissue harbours dominant B-cell and plasma-cell clones associated with autoreactivity. Ann. Rheum. Dis. 73756–62 [Google Scholar]
  197. Ishigaki K, Shoda H, Kochi Y, Yasui T, Kadono Y. 197.  et al. 2015. Quantitative and qualitative characterization of expanded CD4+ T cell clones in rheumatoid arthritis patients. Sci. Rep. 512937 [Google Scholar]
  198. McCarthy MI, Abecasis GR, Cardon LR, Goldstein DB, Little J. 198.  et al. 2008. Genome-wide association studies for complex traits: Consensus, uncertainty and challenges. Nat. Rev. Genet. 9356–69 [Google Scholar]
  199. Albert FW, Kruglyak L. 199.  2015. The role of regulatory variation in complex traits and disease. Nat. Rev. Genet. 16:197–212 [Google Scholar]
  200. Westra HJ, Peters MJ, Esko T, Yaghootkar H, Schurmann C. 200.  et al. 2013. Systematic identification of trans eQTLs as putative drivers of known disease associations. Nat. Genet. 451238–43 [Google Scholar]
  201. Corradin O, Saiakhova A, Akhtar-Zaidi B, Myeroff L, Willis J. 201.  et al. 2014. Combinatorial effects of multiple enhancer variants in linkage disequilibrium dictate levels of gene expression to confer susceptibility to common traits. Genome Res. 24:1–13 [Google Scholar]
  202. Okada Y, Wu D, Trynka G, Raj T, Terao C. 202.  et al. 2014. Genetics of rheumatoid arthritis contributes to biology and drug discovery. Nature 506376–81 [Google Scholar]
  203. Walsh AM, Whitaker JW, Huang CC, Cherkas Y, Lamberth SL. 203.  et al. 2016. Integrative genomic deconvolution of rheumatoid arthritis GWAS loci into gene and cell type associations. Genome Biol. 1779 [Google Scholar]
  204. Lessard CJ, Li H, Adrianto I, Ice JA, Rasmussen A. 204.  et al. 2013. Variants at multiple loci implicated in both innate and adaptive immune responses are associated with Sjögren's syndrome. Nat. Genet. 451284–92 [Google Scholar]
  205. Tewhey R, Kotliar D, Park DS, Liu B, Winnicki S. 205.  et al. 2016. Direct identification of hundreds of expression-modulating variants using a multiplexed reporter assay. Cell 165:1519–29 [Google Scholar]
  206. Peters JE, Lyons PA, Lee JC, Richard AC, Fortune MD. 206.  et al. 2016. Insight into genotype-phenotype associations through eQTL mapping in multiple cell types in health and immune-mediated disease. PLOS Genet. 12e1005908 [Google Scholar]
  207. Fairfax BP, Makino S, Radhakrishnan J, Plant K, Leslie S. 207.  et al. 2012. Genetics of gene expression in primary immune cells identifies cell type-specific master regulators and roles of HLA alleles. Nat. Genet. 44502–10 [Google Scholar]
  208. Farh KK, Marson A, Zhu J, Kleinewietfeld M, Housley WJ. 208.  et al. 2015. Genetic and epigenetic fine mapping of causal autoimmune disease variants. Nature 518:337–43 [Google Scholar]
  209. Lee JC, Espeli M, Anderson CA, Linterman MA, Pocock JM. 209.  et al. 2013. Human SNP links differential outcomes in inflammatory and infectious disease to a FOXO3-regulated pathway. Cell 155:57–69 [Google Scholar]
  210. Lynch KW. 210.  2004. Consequences of regulated pre-mRNA splicing in the immune system. Nat. Rev. Immunol. 4931–40 [Google Scholar]
  211. Wahl MC, Will CL, Luhrmann R. 211.  2009. The spliceosome: design principles of a dynamic RNP machine. Cell 136:701–18 [Google Scholar]
  212. Nilsen TW, Graveley BR. 212.  2010. Expansion of the eukaryotic proteome by alternative splicing. Nature 463457–63 [Google Scholar]
  213. Braunschweig U, Gueroussov S, Plocik AM, Graveley BR, Blencowe BJ. 213.  2013. Dynamic integration of splicing within gene regulatory pathways. Cell 152:1252–69 [Google Scholar]
  214. Martinez NM, Lynch KW. 214.  2013. Control of alternative splicing in immune responses: Many regulators, many predictions, much still to learn. Immunol. Rev. 253:216–36 [Google Scholar]
  215. Ueda H, Howson JM, Esposito L, Heward J, Snook H. 215.  et al. 2003. Association of the T-cell regulatory gene CTLA4 with susceptibility to autoimmune disease. Nature 423:506–11 [Google Scholar]
  216. Gu M, Kakoulidou M, Giscombe R, Pirskanen R, Lefvert AK. 216.  et al. 2008. Identification of CTLA-4 isoforms produced by alternative splicing and their association with myasthenia gravis. Clin. Immunol. 128:374–81 [Google Scholar]
  217. Sestak AL, Nath SK, Sawalha AH, Harley JB. 217.  2007. Current status of lupus genetics. Arthritis Res. Ther. 9210 [Google Scholar]
  218. Kozyrev SV, Abelson AK, Wojcik J, Zaghlool A, Linga Reddy MV. 218.  et al. 2008. Functional variants in the B-cell gene BANK1 are associated with systemic lupus erythematosus. Nat. Genet. 40211–16 [Google Scholar]
  219. Tsuzaka K, Fukuhara I, Setoyama Y, Yoshimoto K, Suzuki K. 219.  et al. 2003. TCRζ mRNA with an alternatively spliced 3′-untranslated region detected in systemic lupus erythematosus patients leads to the down-regulation of TCRζ and TCR/CD3 complex. J. Immunol. 171:2496–503 [Google Scholar]
  220. Tsuzaka K, Setoyama Y, Yoshimoto K, Shiraishi K, Suzuki K. 220.  et al. 2005. A splice variant of the TCRζ mRNA lacking exon 7 leads to the down-regulation of TCRζ, the TCR/CD3 complex, and IL-2 production in systemic lupus erythematosus T cells. J. Immunol. 174:3518–25 [Google Scholar]
  221. Moulton VR, Grammatikos AP, Fitzgerald LM, Tsokos GC. 221.  2013. Splicing factor SF2/ASF rescues IL-2 production in T cells from systemic lupus erythematosus patients by activating IL-2 transcription. PNAS 110:1845–50 [Google Scholar]
  222. Feng D, Sangster-Guity N, Stone R, Korczeniewska J, Mancl ME. 222.  et al. 2010. Differential requirement of histone acetylase and deacetylase activities for IRF5-mediated proinflammatory cytokine expression. J. Immunol. 185:6003–12 [Google Scholar]
  223. Mancl ME, Hu G, Sangster-Guity N, Olshalsky SL, Hoops K. 223.  et al. 2005. Two discrete promoters regulate the alternatively spliced human interferon regulatory factor-5 isoforms. Multiple isoforms with distinct cell type-specific expression, localization, regulation, and function. J. Biol. Chem. 280:21078–90 [Google Scholar]
  224. Stone RC, Feng D, Deng J, Singh S, Yang L. 224.  et al. 2012. Interferon regulatory factor 5 activation in monocytes of systemic lupus erythematosus patients is triggered by circulating autoantigens independent of type I interferons. Arthritis Rheum. 64788–98 [Google Scholar]
  225. Stone RC, Du P, Feng D, Dhawan K, Ronnblom L. 225.  et al. 2013. RNA-Seq for enrichment and analysis of IRF5 transcript expression in SLE. PLOS ONE 8e54487 [Google Scholar]
  226. Richez C, Yasuda K, Bonegio RG, Watkins AA, Aprahamian T. 226.  et al. 2010. IFN regulatory factor 5 is required for disease development in the FcγRIIB−/−Yaa and FcγRIIB−/− mouse models of systemic lupus erythematosus. J. Immunol. 184:796–806 [Google Scholar]
  227. Alevizos I, Illei GG. 227.  2010. microRNAs as biomarkers in rheumatic diseases. Nat. Rev. Rheumatol. 6391–98 [Google Scholar]
  228. Ravenscroft JC, Suri M, Rice GI, Szynkiewicz M, Crow YJ. 228.  2011. Autosomal dominant inheritance of a heterozygous mutation in SAMHD1 causing familial chilblain lupus. Am. J. Med. Genet. A 155A235–37 [Google Scholar]
  229. Roberts RJ, Carneiro MO, Schatz MC. 229.  2013. The advantages of SMRT sequencing. Genome Biol. 14405 [Google Scholar]
  230. Macosko EZ, Basu A, Satija R, Nemesh J, Shekhar K. 230.  et al. 2015. Highly parallel genome-wide expression profiling of individual cells using nanoliter droplets. Cell 161:1202–14 [Google Scholar]
  231. Barnett CP, Todd EJ, Ong R, Davis MR, Atkinson V. 231.  et al. 2014. Distal arthrogryposis type 5D with novel clinical features and compound heterozygous mutations in ECEL1. Am. J. Med. Genet. A 164A1846–49 [Google Scholar]
  232. Kostic AD, Gevers D, Siljander H, Vatanen T, Hyotylainen T. 232.  et al. 2015. The dynamics of the human infant gut microbiome in development and in progression toward type 1 diabetes. Cell Host Microbe 17:260–73 [Google Scholar]
  233. Haberman Y, Tickle TL, Dexheimer PJ, Kim MO, Tang D. 233.  et al. 2014. Pediatric Crohn disease patients exhibit specific ileal transcriptome and microbiome signature. J. Clin. Investig. 124:3617–33 [Google Scholar]
  234. Vatanen T, Kostic AD, d'Hennezel E, Siljander H, Franzosa EA. 234.  et al. 2016. Variation in microbiome LPS immunogenicity contributes to autoimmunity in humans. Cell 165:842–53 [Google Scholar]
  235. Shaw KA, Bertha M, Hofmekler T, Chopra P, Vatanen T. 235.  et al. 2016. Dysbiosis, inflammation, and response to treatment: a longitudinal study of pediatric subjects with newly diagnosed inflammatory bowel disease. Genome Med. 875 [Google Scholar]
  236. 236. Int. Cancer Genome Consort., Hudson TJ, Anderson W, Artez A, Barker AD et al. 2010. International network of cancer genome projects. Nature 464:993–98 Corrigendum. 2010 Nature 465:966 [Google Scholar]
  237. Netea MG, Joosten LA, Li Y, Kumar V, Oosting M. 237.  et al. 2016. Understanding human immune function using the resources from the Human Functional Genomics Project. Nat. Med. 22:831–33 [Google Scholar]
  238. Collins FS, Varmus H. 238.  2015. A new initiative on precision medicine. N. Engl. J. Med. 372793–95 [Google Scholar]
  239. Crow YJ, Chase DS, Lowenstein Schmidt J, Szynkiewicz M, Forte GM. 239.  et al. 2015. Characterization of human disease phenotypes associated with mutations in TREX1, RNASEH2A, RNASEH2B, RNASEH2C, SAMHD1, ADAR, and IFIH1. Am. J. Med. Genet. A 167A296–312 [Google Scholar]
  240. Zhang X, Bogunovic D, Payelle-Brogard B, Francois-Newton V, Speer SD. 240.  et al. 2015. Human intracellular ISG15 prevents interferon-α/β over-amplification and auto-inflammation. Nature 51789–93 [Google Scholar]
  241. Meuwissen ME, Schot R, Buta S, Oudesluijs G, Tinschert S. 241.  et al. 2016. Human USP18 deficiency underlies type 1 interferonopathy leading to severe pseudo-TORCH syndrome. J. Exp. Med. 213:1163–74 [Google Scholar]
  242. Liu Y, Ramot Y, Torrelo A, Paller AS, Si N. 242.  et al. 2012. Mutations in proteasome subunit beta type 8 cause chronic atypical neutrophilic dermatosis with lipodystrophy and elevated temperature with evidence of genetic and phenotypic heterogeneity. Arthritis Rheum. 64895–907 [Google Scholar]
  243. Zhou Q, Yang D, Ombrello AK, Zavialov AV, Toro C. 243.  et al. 2014. Early-onset stroke and vasculopathy associated with mutations in ADA2. N. Engl. J. Med. 370911–20 [Google Scholar]
  244. Liu Y, Jesus AA, Marrero B, Yang D, Ramsey SE. 244.  et al. 2014. Activated STING in a vascular and pulmonary syndrome. N. Engl. J. Med. 371507–18 [Google Scholar]
  245. Jang MA, Kim EK, Now H, Nguyen NT, Kim WJ. 245.  et al. 2015. Mutations in DDX58, which encodes RIG-I, cause atypical Singleton-Merten syndrome. Am. J. Hum. Genet. 96266–74 [Google Scholar]
  246. Briggs TA, Rice GI, Daly S, Urquhart J, Gornall H. 246.  et al. 2011. Tartrate-resistant acid phosphatase deficiency causes a bone dysplasia with autoimmunity and a type I interferon expression signature. Nat. Genet. 43127–31 [Google Scholar]
  247. Park J, Munagala I, Xu H, Blankenship D, Maffucci P. 247.  et al. 2013. Interferon signature in the blood in inflammatory common variable immune deficiency. PLOS ONE 8:e74893 [Google Scholar]
  248. Smith EJ, Allantaz F, Bennett L, Zhang D, Gao X. 248.  et al. 2010. Clinical, molecular, and genetic characteristics of PAPA syndrome: a review. Curr. Genom. 11:519–27 [Google Scholar]
/content/journals/10.1146/annurev-immunol-051116-052225
Loading
/content/journals/10.1146/annurev-immunol-051116-052225
Loading

Data & Media loading...

  • Article Type: Review Article
This is a required field
Please enter a valid email address
Approval was a Success
Invalid data
An Error Occurred
Approval was partially successful, following selected items could not be processed due to error