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Profiles of gene expression in human autoimmune disease

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Abstract

Human autoimmune diseases arise from complex interactions between genetic and environmental factors, result from immune attack upon target tissues, and affect 3–5% of the population. We compared gene expression profiles (>4000 genes) in the peripheral blood mononuclear cells of normal individuals after immunization to individuals with four different autoimmune diseases (rheumatoid arthritis, systemic lupus erythematosus, insulin-dependent diabetes mellitus, and multiple sclerosis). All autoimmune individuals, including unaffected first-degree relatives, share a common gene expression profile that is completely distinct from the immune profile. Therefore, this expression pattern is not simply a recapitulation of the immune response to nonself, is not a result of the disease process, and results, as least in part, from genetic factors. Surprisingly, these genes are clustered in chromosomal domains suggesting there is some genomewide logic to this unique expression pattern. These data argue that that there is a constant pattern of gene expression in autoimmunity that is independent of the specific autoimmune disease and clinical parameters associated with any individual autoimmune disease.

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References

  1. Jacobson, D. L., Gange, S. J., Rose, N. R., and Graham, N. M. (1997) Epidemiology and estimated population burden of selected autoimmune diseases in the United States. Clin. Immunol. Immunopathol. 84, 223–243.

    Article  PubMed  CAS  Google Scholar 

  2. Olsen, N. J. and Kovacs, W. J. (1996) Gonadal steroids and immunity. Endocr. Rev. 17, 369–384.

    Article  PubMed  CAS  Google Scholar 

  3. Pincus, T., Sokka, T., and Wolfe, F. (2001) Premature mortality in patients with rheumatoid arthritis: evolving concepts. Arthritis Rheum. 44, 1234–1236.

    Article  PubMed  CAS  Google Scholar 

  4. Cervera, R., Khamashta, M. A., Font, J., Sebastiani, G. D., Gil, A., Lavilla, P., et al. (1999) Morbidity and mortality in systemic lupus erythematosus during a 5-year period. A multicenter prospective study of 1,000 patients. European Working Party on Systemic Lupus Erythematosus. Medicine (Baltimore) 78, 167–175.

    Article  CAS  Google Scholar 

  5. Sokka, T. and Pincus, T. (2001) Markers for work disability in rheumatoid arthritis. J. Rheumatol. 28, 1718–1722.

    PubMed  CAS  Google Scholar 

  6. Kaltenhauser, S., Wagner, U., Schuster, E., Wassmuth, R., Arnold, S., Seidel, W., et al. (2001) Immunogenetic markers and seropositivity predict radiological progression in early rheumatoid arthritis independent of disease activity. J. Rheumatol 28, 735–744.

    PubMed  CAS  Google Scholar 

  7. Pascual, M., Mataran, L., Jones, G., Shing, D., van der Slik, A. R., Giphart, M. J., et al. (2002) HLA haplotypes and susceptibility to rheumatoid arthritis. More than class II genes. Scand. J. Rheumatol. 31, 275–278.

    Article  PubMed  CAS  Google Scholar 

  8. Becker, K. G., Simon, R. M., Bailey-Wilson, J. E., Freidlin, B., Biddison, W. E., McFarland, H. F., et al. (1998) Clustering of non-major histocompatibility complex susceptibility candidate loci in human autoimmune diseases. Proc. Natl. Acad. Sci. USA 95, 9979–9984.

    Article  PubMed  CAS  Google Scholar 

  9. Lin, J. P., Cash, J. M., Doyle, S. Z., Peden, S., Kanik, K., Amos, C. I., et al. (1998) Familial clustering of rheumatoid arthritis with other autoimmune diseases. Hum. Genet. 103, 475–482.

    Article  PubMed  CAS  Google Scholar 

  10. Cohen, M. G. and Webb, J. (1987) Concurrence of rheumatoid arthritis and systemic lupus erythematosus: report of 11 cases. Ann. Rheum Dis. 46, 853–858.

    Article  PubMed  CAS  Google Scholar 

  11. Edberg, J. C., Langefeld, C. D., Wu, J., Moser, K. L., Kaufman, K. M., Kelly, J., et al. (2002) Genetic linkage and association of Fcgamma receptor IIIA (CD16A) on chromosome 1q23 with human systemic lupus erythematosus. Arthritis Rheum. 46, 2132–2140.

    Article  PubMed  CAS  Google Scholar 

  12. Namjou, B., Nath, S. K., Kilpatrick, J., Kelly, J. A., Reid, J., James, J. A., et al. (2002) Stratification of pedigrees multiplex for systemic lupus erythematosus and for self-reported rheumatoid arthritis detects a systemic lupus erythematosus susceptibility gene (SLER1) at 5p 15.3. Arthritis Rheum. 46, 2937–2945.

    Article  PubMed  CAS  Google Scholar 

  13. Maas, K., Chan, S., Parker, J., Slater, A., Moore, J., Olsen, N., et al. (2002) Cutting edge: molecular portrait of human autoimmune disease. J. Immunol. 169, 5–9.

    PubMed  CAS  Google Scholar 

  14. Eisen, M. B., Spellman, P. T., Brown, P. O., and Botstein, D. (1998) Cluster analysis and display of genome-wide expression patterns. Proc. Natl. Acad. Sci. USA 95, 14863–14868.

    Article  PubMed  CAS  Google Scholar 

  15. Sherlock, G. (2000) Analysis of large-scale gene expression data. Curr. Opin. Immunol. 12, 201–205.

    Article  PubMed  CAS  Google Scholar 

  16. Krichevsky, A. M., Metzer, E., and Rosen, H. 1999. Translational control of specific genes during differentiation of HL-60 cells. J. Biol. Chem 274, 14295–14305.

    Article  PubMed  CAS  Google Scholar 

  17. Marrack, P., Kappler, J. and Kotzin, B. L. (2001) Autoimmune disease: why and where it occurs. Nat. Med. 7, 899–905.

    Article  PubMed  CAS  Google Scholar 

  18. Amundson, S. A., Myers, T. G., and Fornance A. J., Jr. (1998) Roles for p53 in growth arrest and apoptosis: putting on the brakes after genotoxic stress. Oncogene 17, 3287–3291.

    Article  PubMed  Google Scholar 

  19. Zhao, R., Gish, K., Murphy, M., Yin, Y., Notterman, D., Hoffman, W. H., et al. (2000) Analysis of p53-regulated gene expression patterns using oligonucleotide arrays. Genes Dev. 14, 981–993.

    Article  PubMed  CAS  Google Scholar 

  20. Kannan, K., Kaminski, N., Rechavi, G., Jakob-Hirsch, J., Amariglio, N., and Givol, D. (2001) DNA microarrays identification of primary and secondary target genes regulated by p53. Oncogene 20, 225–2234.

    Google Scholar 

  21. Bradley, J. V. (1968) Distribution-free statistical tests. Prentice-Hall, Englewood Cliffs, NJ.

    Google Scholar 

  22. Brem, R. B., Yvert, G., Clinton, R., and Kruglyak L. (2002) Genetic dissection of transcriptional regulation in budding yeast. Science 296, 752–755.

    Article  PubMed  CAS  Google Scholar 

  23. Caron, H., van Schaik, B., van der Mee, M., Baas, F., Riggins, G., van Sluis, P., et al. (2001) The human transcriptome map: clustering of highly expressed genes in chromosomal domains. Science 291, 1289–1292.

    Article  PubMed  CAS  Google Scholar 

  24. Venter, J. C. et al. (2001) The sequence of the human genome. Science 291, 1304–1351.

    Article  PubMed  CAS  Google Scholar 

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Correspondence to Thomas M. Aune.

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Aune, T.M., Maas, K., Parker, J. et al. Profiles of gene expression in human autoimmune disease. Cell Biochem Biophys 40, 81–96 (2004). https://doi.org/10.1385/CBB:40:2:081

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