Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Full Paper
  • Published:

Analysis of gene expression profiles in human systemic lupus erythematosus using oligonucleotide microarray

Genes & Immunity volume 4, pages 177–186 (2003)Cite this article

Abstract

Epidemiologic studies suggest a strong genetic component for susceptibility to systemic lupus erythematosus (SLE). To investigate the genetic mechanism of pathogenesis of SLE, we studied the difference in gene expression of peripheral blood cells between 10 SLE patients and 18 healthy controls using oligonucleotide microarray. When gene expression for patients was compared to the mean of normal controls, among the 3002 target genes, 61 genes were identified with greater than a two-fold change difference in expression level. Of these genes, 24 were upregulated and 37 downregulated in at least half of the patients. By the Welch's ANOVA/Welch's t-test, all these 61 genes were significantly different (P<0.05) between SLE patients and normal controls. Among these genes with differential expression, IFN-ω and Ly6E (TSA-1/Sca-2) may play an important role in the mechanism of SLE pathogenesis. TSA-1 antigens may represent an important alternative pathway for T-cell activation that may be involved in IFN-mediated immunomodulation. Hierarchical clustering showed that patient samples were clearly separated from controls based on their gene expression profile. These results demonstrate that high-density oligonucleotide microarray has the potential to explore the mechanism of pathogenesis of systemic lupus erythematosus.

This is a preview of subscription content, access via your institution

Access options

Buy this article

  • Purchase on Springer Link
  • Instant access to full article PDF
Buy now

Prices may be subject to local taxes which are calculated during checkout

Figure 1
Figure 2

Similar content being viewed by others

Accession codes

Accessions

GenBank/EMBL/DDBJ

References

  1. Hochberg MC . The epidemiology of systemic lupus erythematosus. In: Wallace DJ, Hahn BH (eds). Dubois’ Lupus Erythematosus. Williams and Wilkins: Baltimore, 1997, pp 49–65.

    Google Scholar 

  2. Wakeland EK, Liu K, Graham RR, Behrens TW . Delineating the genetic basis of systemic lupus erythematosus. Immunity 2001; 15: 397–408.

    Article  CAS  PubMed  Google Scholar 

  3. Deapen DM, Escalante A, Weinrib L, Horwitz DA, Mack M . A revised estimate of twin concordance in systemic lupus erythematosus. Arthritis Rheum 1992; 35: 311–318.

    Article  CAS  PubMed  Google Scholar 

  4. Vyse TJ, Todd JA . Genetic analysis of autoimmune diseases. Cell 1996; 85: 311–318.

    Article  CAS  PubMed  Google Scholar 

  5. Arnett FC . The genetic basis of lupus erythematosus. In: Wallace DJ, Hahn BH (eds). Dubois’ Lupus Erythematosus. Williams and Wilkins: Baltimore, 1997, pp 77–117.

    Google Scholar 

  6. Wu J, Edberg JC, Redecha PB et al. A novel polymorphism of Fcγ RIIIa(CD16) alters receptor function and predisposes to autoimmune disease. J Clin Invest 1997; 100: 1059–1070.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  7. Tsao BP, Cantor RM, Kalunian KC et al. Evidence for linkage of a candidate chromosome 1 region to human systemic lupus erythematosus. J Clin Invest 1997; 99: 725–731.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  8. Shai R, Quismorio FP, Li L et al. Genome-wide screen for systemic lupus erythematosus susceptibility genes in multiplex families. Hum Mol Genet 1999; 8: 639–644.

    Article  CAS  PubMed  Google Scholar 

  9. Gaffney PM, Kearns GM, Shark KB et al. A genome-wide search for susceptibility genes in human systemic lupus erythematosus sib-pair families. Proc Natl Acad Sci USA 1998; 95: 14875–14879.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  10. Gaffney PM, Ortmann WA, Selby SA et al. Genome screening in human systemic lupus erythematosus: results from a second Minnesota cohort and combined analyses of sib-pair families. Am J Hum Genet 2000; 66: 547–556.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  11. Brown PO, Hartwell L . Genomics and human disease-variations on variation. Nature Genet 1998; 18: 91–93.

    Article  CAS  PubMed  Google Scholar 

  12. Derisi JL, Lyer VR, Brown PO . Exploring the metabolic and genetic control of gene expression on a genomic scale. Science 1997; 278: 680–686.

    Article  CAS  PubMed  Google Scholar 

  13. Schena M, Shalon D, Davis RW et al. Quantitative monitoring of gene expression patterns with a complementary DNA microarray. Science 1995; 270: 467–470.

    Article  CAS  PubMed  Google Scholar 

  14. Heller RA, Schena M, Chai A et al. Discovery and analysis of inflammatory disease-related genes using cDNA microarrays. Proc Natl Acad Sci USA 1997; 94: 2150–2155.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  15. Lawrance IC, Fiocchi C, Chakravarti S . Ulcerative colitis and Crohn's diseases: distinctive gene expression profiles and novel susceptibility candidate genes. Hum Mol Genet 2001; 10: 445–456.

    Article  CAS  PubMed  Google Scholar 

  16. Staudt LM . Gene expression physiology and pathophysiology of the immune system. Trends Immunol 2001; 22: 35–40.

    Article  CAS  PubMed  Google Scholar 

  17. Rus V, Atamas SP, Shustova V et al. Expression of cytokin- and chemokine-related genes in peripheral blood mononuclear cells from lupus patients by cDNA array. Clin Immunol 2002; 102: 283–290.

    Article  CAS  PubMed  Google Scholar 

  18. Taniguchi M, Miura K, Iwao H, and Yamanaka S . Quantitative assessment of DNA microarray—comparison with Northern blot analyses. Genomics 2001; 71: 34–39.

    Article  CAS  PubMed  Google Scholar 

  19. Von Wussow P, Jakschies D, Hartung K, Deicher H . Presence of interferon and anti-interferon in patients with systemic lupus erythematosus. Rheumatol Int 1988; 8: 225–230.

    Article  CAS  PubMed  Google Scholar 

  20. Preble OT, Rothko K, Klippel JH, Friedman RM, Johnston MI . Interferon-induced 2’-5’adenylate synthetase in vivo and interferon production in vitro by lymphocytes from systemic lupus erythematosus patients with and without circulating interferon. J Exp Med 1983; 157: 2140–2146.

    Article  CAS  PubMed  Google Scholar 

  21. Hylton W, Cayley J, Dore C, Denman AM . 2’,5’-Oligoadenylate synthetase induction in lymphocytes of patients with connective tissue diseases. Ann Rheum Dis 1986; 45: 220–224.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  22. Tsao BP, Cantor RM, Grossman JM et al. PARP alleles within the linked chromosomal region are associated with systemic lupus erythematosus. J Clin Invest 1999; 103: 1135–1140.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  23. Raziuddin S, Al-Janadi MA, Alwabel AA . T-cell receptor α/β chain-CD3 protein complex defect in systemic lupus erythematosus: T-cell function. Am J Med 1992; 93: 461–466.

    Article  CAS  PubMed  Google Scholar 

  24. Ytterberg SR, Schnitzer TJ . Serum interferon levels in patients with systemic lupus erythematosus. Arthritis Rheum 1982; 25: 401–406.

    Article  CAS  PubMed  Google Scholar 

  25. Hauptmann R, Swetly P . A novel class of human type I interferons. Nucleic Acids Res 1985; 13: 4739–4749.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  26. Adolf GR . Monoclonal antibodies and enzyme immunoassays specific for human interferon (IFN) ω 1: evidence that IFN- ω 1 is a component of human leukocyte IFN. Virology 1990; 175: 410–417.

    Article  CAS  PubMed  Google Scholar 

  27. Cederblad B, Blomberg S, Vallin H et al. Patients with systemic lupus erythematosus have reduced numbers of circulating natural interferon-alpha-producing cells. J Autoimmunol 1998; 11: 465–470.

    Article  CAS  Google Scholar 

  28. Blomberg S, Eloranta ML, Cederblad B et al. Presence of cutaneous interferon-α producing cells in patients with systemic lupus erythematosus. Lupus 2001; 10: 484–490.

    Article  CAS  PubMed  Google Scholar 

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

    Article  CAS  PubMed  Google Scholar 

  30. Ronnblom LE, Alm GV, Oberg KE . Autoimmunity after alpha-interferon therapy for malignant carcinoid tumour. Ann Intern Med 1991; 115: 178–183.

    Article  CAS  PubMed  Google Scholar 

  31. Neubauer RH, Goldstein L, Rabin H, Stebbing N . Stimulation of in vitro immunoglobulin production by interferon-α. J Immunol 1985; 134: 299–303.

    CAS  PubMed  Google Scholar 

  32. Marrack P, Kappler J, Mitchell T . Type I interferon keep activated T cells alive. J Exp Med 1999; 189: 521–529.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  33. Su L, David M . Inhibition of B cell receptor-mediated apoptosis by IFN. J Immunol 1999; 162: 6317–6321.

    CAS  PubMed  Google Scholar 

  34. Blanco P, Palucka AK, Gill M, Pascual V, Banchereau J . Induction of dendritic cell differentiation by IFN-α in systemic lupus erythematosus. Science 2001; 294: 1540–1543.

    Article  CAS  PubMed  Google Scholar 

  35. Ronnblom L, Alm GV . An etiopathogenic role for the type I IFN system in SLE. Trends Immunol 2001; 22: 427–431.

    Article  CAS  PubMed  Google Scholar 

  36. Shan XC, Bourdeau A, Rhoton A et al. Characterization and mapping to human chromosome 8q24.3 of Ly-6-related gene 9804 encoding an apparent homologue of mouse TSA-1. J Immunol 1998; 160: 197–208.

    CAS  PubMed  Google Scholar 

  37. Godfrey DI, Masciantonio M, Tucek CL et al. Thymic shared antigen-1, a novel thymocyte marker discriminating immature from mature thymocyte subsets. J Immunol 1992; 148: 2006–2011.

    CAS  PubMed  Google Scholar 

  38. Liossis SC, Ding XZ, Dennis GJ, Tsokos GC . Altered pattern of TCR/CD3-mediated protein-tyrosyl phosphorylation in T cells from patients with systemic lupus erythematosus. J Clin Invest 1998; 101: 1448–1457.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  39. Brundula V, Rivas LJ, Blasini AM et al. Diminished levels of T cell receptor ζ chains in peripheral blood T lymphocytes from patients with systemic lupus erythematosus. Arthritis Rheum 1999; 42: 1908–1916.

    Article  CAS  PubMed  Google Scholar 

  40. Noda S, Kosugi A, Saitoh SI, Narumiya S, Hamaoka T . Protection from anti-TCR/CD3-induced apoptosis in immature thymocytes by a signal through thymic shared antigen-1/stem cell antigen-2. J Exp Med 1996; 183: 2355–2360.

    Article  CAS  PubMed  Google Scholar 

  41. Saitoh SI, Kosugi A, Noda S et al. Modulation of TCR-mediated signaling pathway by thymic shared antigen-1(TSA-1)/stem cell antigen-2(Sca-2). J Immunol 1995; 155: 5574–5581.

    CAS  PubMed  Google Scholar 

  42. Dumont FJ, Coker LZ . Interferon-α/β enhances the expression of Ly-6 antigens on T cells in vivo and in vitro. Eur J Immunol 1986; 16: 735–740.

    Article  CAS  PubMed  Google Scholar 

  43. Golub TR, Slonim DK, Tamayo P et al. Molecular classification of cancer: class discovery and class prediction by gene expression monitoring. Science 1999; 286: 531–537.

    Article  CAS  PubMed  Google Scholar 

  44. Tan EM, Cohen AS, Fries JF et al. The 1982 revised criteria for the classification of systemic lupus erythematosus. Arthritis Rheumatosus 1982; 25: 1271–1277.

    Article  CAS  Google Scholar 

  45. Bombardier C, Gladman DD, Urowitz MB, Caron D, Chang CH . Derivation of the SLEDAI: a disease activity index for lupus patients. The Committee on Prognosis Studies in SLE. Arthritis Rheum 1992; 35: 630–640.

    Article  CAS  PubMed  Google Scholar 

  46. Lockhart DJ, Winzeler EA . Genomics, gene expression and DNA arrays. Nature 2000; 405: 827–836.

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgements

This work was supported by the National Nature Science Foundation of China (No. 39730430). We thank the patients for providing the blood samples.

Author information

Authors and Affiliations

  1. Department of Rheumatology, Nanjing First Hospital, Nanjing Medical University, China

    G-M Han

  2. Shanghai Institute of Rheumatology, Second Medical University, Shanghai, China

    S-L Chen, N Shen, S Ye, C-D Bao & Y-Y Gu

Authors
  1. G-M Han
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. S-L Chen
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. N Shen
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. S Ye
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. C-D Bao
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Y-Y Gu
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to G-M Han.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Han, GM., Chen, SL., Shen, N. et al. Analysis of gene expression profiles in human systemic lupus erythematosus using oligonucleotide microarray. Genes Immun 4, 177–186 (2003). https://doi.org/10.1038/sj.gene.6363966

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/sj.gene.6363966

Keywords

This article is cited by

Search

Advanced search

Quick links