Translational Research
Volume 155, Issue 3 , Pages 109-117 , March 2010

Genetic regulation of serum cytokines in systemic lupus erythematosus

  • Silvia N. Kariuki
  • ,
  • Timothy B. Niewold

      Affiliations

    • Corresponding Author InformationReprint requests: Timothy B. Niewold, MD, Section of Rheumatology, University of Chicago, 5841 S. Maryland Avenue, MC 0930, Chicago, IL 60637

Received 20 July 2009 ,Revised 27 August 2009 ,Accepted 28 August 2009.

References 

  1. Chun HY, Chung JW, Kim HA, et al. Cytokine IL-6 and IL-10 as biomarkers in systemic lupus erythematosus. J Clin Immunol. 2007;27:461–466
  2. Liu TF, Jones BM. Impaired production of IL-12 in system lupus erythematosus. II: IL-12 production in vitro is correlated negatively with serum IL-10, positively with serum IFN-gamma and negatively with disease activity in SLE. Cytokine. 1998;10:148–153
  3. Grondal G, Gunnarsson I, Ronnelid J, Rogberg S, Klareskog L, Lundberg I. Cytokine production, serum levels and disease activity in systemic lupus erythematosus. Clin Exp Rheumatol. 2000;18:565–570
  4. Rahman A, Isenberg DA. Systemic lupus erythematosus. N Engl J Med. 2008;358:929–939
  5. Kariuki SN, Crow MK, Niewold TB. The PTPN22 C1858T polymorphism is associated with skewing of cytokine profiles toward high interferon-alpha activity and low tumor necrosis factor alpha levels in patients with lupus. Arthritis Rheum. 2008;58:2818–2823
  6. Studnicka-Benke A, Steiner G, Petera P, Smolen JS. Tumour necrosis factor alpha and its soluble receptors parallel clinical disease and autoimmune activity in systemic lupus erythematosus. Br J Rheumatol. 1996;35:1067–1074
  7. Kariuki SN, Moore JG, Kirou KA, Crow MK, Utset TO, Niewold TB. Age- and gender-specific modulation of serum osteopontin and interferon-alpha by osteopontin genotype in systemic lupus erythematosus. Genes Immun. 2009;10:487–494
  8. Hooks JJ, Moutsopoulos HM, Geis SA, Stahl NI, Decker JL, Notkins AL. Immune interferon in the circulation of patients with autoimmune disease. N Engl J Med. 1979;301:5–8
  9. Niewold TB. Interferon alpha-induced lupus: proof of principle. J Clin Rheumatol. 2008;14:131–132
  10. Crow MK. Type I interferon in systemic lupus erythematosus. Curr Top Microbiol Immunol. 2007;316:359–386
  11. Baechler EC, Batliwalla FM, Karypis G, et al. Interferon-inducible gene expression signature in peripheral blood cells of patients with severe lupus. Proc Natl Acad Sci U S A. 2003;100:2610–2615
  12. Fairhurst AM, Wandstrat AE, Wakeland EK. Systemic lupus erythematosus: multiple immunological phenotypes in a complex genetic disease. Adv Immunol. 2006;92:1–69
  13. Crow MK, Kirou KA, Wohlgemuth J. Microarray analysis of interferon-regulated genes in SLE. Autoimmunity. 2003;36:481–490
  14. Hua J, Kirou K, Lee C, Crow MK. Functional assay of type I interferon in systemic lupus erythematosus plasma and association with anti-RNA binding protein autoantibodies. Arthritis Rheum. 2006;54:1906–1916
  15. Niewold TB, Hua J, Lehman TJ, Harley JB, Crow MK. High serum IFN-alpha activity is a heritable risk factor for systemic lupus erythematosus. Genes Immun. 2007;8:492–502
  16. Landolt-Marticorena C, Bonventi G, Lubovich A, et al. Lack of association between the interferon-alpha signature and longitudinal changes in disease activity in Systemic Lupus Erythematosus. Ann Rheum Dis. 2009;68:1440–1446
  17. Moser KL, Kelly JA, Lessard CJ, Harley JB. Recent insights into the genetic basis of systemic lupus erythematosus. Genes Immun. 2009;10:373–379
  18. Harley IT, Kaufman KM, Langefeld CD, Harley JB, Kelly JA. Genetic susceptibility to SLE: new insights from fine mapping and genome-wide association studies. Nat Rev Genet. 2009;10:285–290
  19. Takaoka A, Yanai H. Interferon signalling network in innate defence. Cell Microbiol. 2006;8:907–922
  20. Kirou KA, Lee C, George S, Louca K, Peterson MG, Crow MK. Activation of the interferon-alpha pathway identifies a subgroup of systemic lupus erythematosus patients with distinct serologic features and active disease. Arthritis Rheum. 2005;52:1491–1503
  21. Ytterberg SR, Schnitzer TJ. Serum interferon levels in patients with systemic lupus erythematosus. Arthritis Rheum. 1982;25:401–406
  22. Niewold TB, Kelly JA, Flesch MH, Espinoza LR, Harley JB, Crow MK. Association of the IRF5 risk haplotype with high serum interferon-alpha activity in systemic lupus erythematosus patients. Arthritis Rheum. 2008;58:2481–2487
  23. Ronnblom LE, Alm GV, Oberg KE. Possible induction of systemic lupus erythematosus by interferon-alpha treatment in a patient with a malignant carcinoid tumour. J Intern Med. 1990;227:207–210
  24. Niewold TB, Swedler WI. Systemic lupus erythematosus arising during interferon-alpha therapy for cryoglobulinemic vasculitis associated with hepatitis C. Clin Rheumatol. 2005;24:178–181
  25. Tsao BP, Grossman JM, Riemekasten G, et al. Familiality and co-occurrence of clinical features of systemic lupus erythematosus. Arthritis Rheum. 2002;46:2678–2685
  26. Ramos PS, Kelly JA, Gray-McGuire C, et al. Familial aggregation and linkage analysis of autoantibody traits in pedigrees multiplex for systemic lupus erythematosus. Genes Immun. 2006;7:417–432
  27. Ioannou Y, Isenberg DA. Current evidence for the induction of autoimmune rheumatic manifestations by cytokine therapy. Arthritis Rheum. 2000;43:1431–1442
  28. Petri M. Epidemiology of systemic lupus erythematosus. Best Pract Res Clin Rheumatol. 2002;16:847–858
  29. Lopez P, Mozo L, Gutierrez C, Suarez A. Epidemiology of systemic lupus erythematosus in a northern Spanish population: gender and age influence on immunological features. Lupus. 2003;12:860–865
  30. Szyper-Kravitz M, Zandman-Goddard G, Lahita RG, Shoenfeld Y. The neuroendocrine-immune interactions in systemic lupus erythematosus: a basis for understanding disease pathogenesis and complexity. Rheum Dis Clin North Am. 2005;31:161–175
  31. van Vollenhoven RF, Engleman EG, McGuire JL. An open study of dehydroepiandrosterone in systemic lupus erythematosus. Arthritis Rheum. 1994;37:1305–1310
  32. Chagnon P, Schneider R, Hebert J, et al. Identification and characterization of an Xp22.33;Yp11.2 translocation causing a triplication of several genes of the pseudoautosomal region 1 in an XX male patient with severe systemic lupus erythematosus. Arthritis Rheum. 2006;54:1270–1278
  33. Stevens AM, Tsao BP, Hahn BH, et al. Maternal HLA class II compatibility in men with systemic lupus erythematosus. Arthritis Rheum. 2005;52:2768–2773
  34. Niewold TB, Adler JE, Glenn SB, Lehman TJ, Harley JB, Crow MK. Age- and sex-related patterns of serum interferon-alpha activity in lupus families. Arthritis Rheum. 2008;58:2113–2119
  35. Denhardt DT, Noda M. Osteopontin expression and function: role in bone remodeling. J Cell Biochem Suppl. 1998;30-31:92–102
  36. Lampe MA, Patarca R, Iregui MV, Cantor H. Polyclonal B cell activation by the Eta-1 cytokine and the development of systemic autoimmune disease. J Immunol. 1991;147:2902–2906
  37. Scatena M, Liaw L, Giachelli CM. Osteopontin: a multifunctional molecule regulating chronic inflammation and vascular disease. Arterioscler Thromb Vasc Biol. 2007;27:2302–2309
  38. Masutani K, Akahoshi M, Tsuruya K, et al. Predominance of Th1 immune response in diffuse proliferative lupus nephritis. Arthritis Rheum. 2001;44:2097–2106
  39. Chabas D, Baranzini SE, Mitchell D, et al. The influence of the proinflammatory cytokine, osteopontin, on autoimmune demyelinating disease. Science. 2001;294:1731–1735
  40. Shinohara ML, Lu L, Bu J, et al. Osteopontin expression is essential for interferon-alpha production by plasmacytoid dendritic cells. Nat Immunol. 2006;7:498–506
  41. Forton AC, Petri MA, Goldman D, Sullivan KE. An osteopontin (SPP1) polymorphism is associated with systemic lupus erythematosus. Hum Mutat. 2002;19:459
  42. D'Alfonso S, Barizzone N, Giordano M, et al. Two single-nucleotide polymorphisms in the 5' and 3' ends of the osteopontin gene contribute to susceptibility to systemic lupus erythematosus. Arthritis Rheum. 2005;52:539–547
  43. Han S, Guthridge JM, Harley IT, et al. Osteopontin and systemic lupus erythematosus association: a probable gene-gender interaction. PLoS ONE. 2008;3:e0001757
  44. Vanacker JM, Delmarre C, Guo X, Laudet V. Activation of the osteopontin promoter by the orphan nuclear receptor estrogen receptor related alpha. Cell Growth Differ. 1998;9:1007–1014
  45. Lee YH, Rho YH, Choi SJ, et al. The PTPN22 C1858T functional polymorphism and autoimmune diseases–a meta-analysis. Rheumatology. 2007;46:49–56
  46. Mavragani CP, Danielides S, Niewold TB, Kirou KA, Moutsopoulos HM, Crow MK. Activation of the type I interferon pathway in autoimmune thyroid disease. Arthritis Rheum. 2007;56:S229
  47. Palucka AK, Blanck JP, Bennett L, Pascual V, Banchereau J. Cross-regulation of TNF and IFN-alpha in autoimmune diseases. Proc Natl Acad Sci U S A. 2005;102:3372–3377
  48. Devendra D, Eisenbarth GS. Interferon alpha—a potential link in the pathogenesis of viral-induced type 1 diabetes and autoimmunity. Clin Immunol. 2004;111:225–233
  49. Walker JG, Ahern MJ, Coleman M, et al. Characterisation of a dendritic cell subset in synovial tissue which strongly expresses Jak/STAT transcription factors from patients with rheumatoid arthritis. Ann Rheum Dis. 2007;66:992–999
  50. Roelofs MF, Wenink MH, Brentano F, et al. Type I interferons might form the link between Toll-like receptor (TLR) 3/7 and TLR4-mediated synovial inflammation in rheumatoid arthritis (RA). Ann Rheum Dis. 2009;68:1486–1493
  51. Barrett JC, Hansoul S, Nicolae DL, et al. Genome-wide association defines more than 30 distinct susceptibility loci for Crohn's disease. Nat Genet. 2008;40:955–962
  52. Rutgeerts P, Vermeire S, Van Assche G. Biological therapies for inflammatory bowel diseases. Gastroenterology. 2009;136:1182–1197
  53. Vang T, Miletic AV, Bottini N, Mustelin T. Protein tyrosine phosphatase PTPN22 in human autoimmunity. Autoimmunity. 2007;40:453–461
  54. Rieck M, Arechiga A, Onengut-Gumuscu S, Greenbaum C, Concannon P, Buckner JH. Genetic variation in PTPN22 corresponds to altered function of T and B lymphocytes. J Immunol. 2007;179:4704–4710
  55. Pierer M, Kaltenhauser S, Arnold S, et al. Association of PTPN22 1858 single-nucleotide polymorphism with rheumatoid arthritis in a German cohort: higher frequency of the risk allele in male compared to female patients. Arthritis Res Ther. 2006;8:R75
  56. Dastmalchi M, Grundtman C, Alexanderson H, et al. A high incidence of disease flares in an open pilot study of infliximab in patients with refractory inflammatory myopathies. Ann Rheum Dis. 2008;67:1670–1677
  57. Mavragani CP, Niewold TB, Moutsopoulos NM, Pillemer SR, Wahl SM, Crow MK. Augmented interferon-alpha pathway activation in patients with Sjogren's syndrome treated with etanercept. Arthritis Rheum. 2007;56:3995–4004
  58. Tyler DR, Persky ME, Matthews LA, Chan S, Farrar JD. Pre-assembly of STAT4 with the human IFN-alpha/beta receptor-2 subunit is mediated by the STAT4 N-domain. Mol Immunol. 2007;44:1864–1872
  59. Remmers EF, Plenge RM, Lee AT, et al. STAT4 and the risk of rheumatoid arthritis and systemic lupus erythematosus. N Engl J Med. 2007;357:977–986
  60. Sigurdsson S, Nordmark G, Garnier S, et al. A risk haplotype of STAT4 for systemic lupus erythematosus is over-expressed, correlates with anti-dsDNA and shows additive effects with two risk alleles of IRF5. Hum Mol Genet. 2008;17:2868–2876
  61. Korman BD, Alba MI, Le JM, et al. Variant form of STAT4 is associated with primary Sjogren's syndrome. Genes Immun. 2008;9:267–270
  62. Prahalad S, Hansen S, Whiting A, et al. Variants in TNFAIP3, STAT4, and C12orf30 loci associated with multiple autoimmune diseases are also associated with juvenile idiopathic arthritis. Arthritis Rheum. 2009;60:2124–2130
  63. Bave U, Nordmark G, Lovgren T, et al. Activation of the type I interferon system in primary Sjogren's syndrome: a possible etiopathogenic mechanism. Arthritis Rheum. 2005;52:1185–1195
  64. Niewold TB, Rivera TL, Buyon JP, Crow MK. Serum type I interferon activity is dependent on maternal diagnosis in anti-SSA/Ro-positive mothers of children with neonatal lupus. Arthritis Rheum. 2008;58:541–546
  65. Taylor KE, Remmers EF, Lee AT, et al. Specificity of the STAT4 genetic association for severe disease manifestations of systemic lupus erythematosus. PLoS Genet. 2008;4:e1000084
  66. Kariuki SN, Kirou KA, MacDermott EJ, Barillas-Arias L, Crow MK, Niewold TB. Cutting edge: autoimmune disease risk variant of STAT4 confers increased sensitivity to IFN-alpha in lupus patients in vivo. J Immunol. 2009;182:34–38
  67. Jacob CO, McDevitt HO. Tumour necrosis factor-alpha in murine autoimmune ‘lupus’ nephritis. Nature. 1988;331:356–358
  68. Aringer M, Smolen JS. The role of tumor necrosis factor-alpha in systemic lupus erythematosus. Arthritis Res Ther. 2008;10:202
  69. Yao Y, Richman L, Higgs BW, et al. Neutralization of interferon-alpha/beta-inducible genes and downstream effect in a phase I trial of an anti-interferon-alpha monoclonal antibody in systemic lupus erythematosus. Arthritis Rheum. 2009;60:1785–1796
  70. Fan K, Dai J, Wang H, et al. Treatment of collagen-induced arthritis with an anti-osteopontin monoclonal antibody through promotion of apoptosis of both murine and human activated T cells. Arthritis Rheum. 2008;58:2041–2052

 Timothy B. Niewold, MD is an Assistant Professor of Medicine, Section of Rheumatology, University of Chicago. His article is based on a presentation given at the Combined Annual Meeting of the Central Society for Clinical Research and Midwestern Section American Federation for Medical Research held in Chicago, Ill, April 2009.

 Supported by National Institutes of Health Grant K08 AI083790, NIAID Clinical Research Loan Repayment Grant AI071651, Arthritis National Research Foundation Eng Tan Scholar Award, University of Chicago CTSA Core Subsidy Grant and Collaborative University of Chicago/Northshore University Health System Translational Research Pilot Grant RR024999 from UL1.

PII: S1931-5244(09)00269-2

doi: 10.1016/j.trsl.2009.08.012

Translational Research
Volume 155, Issue 3 , Pages 109-117 , March 2010