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. 2004 May;63(5):578–582. doi: 10.1136/ard.2003.012948

Autoimmune manifestations in human myelodysplasia: a positive correlation with interferon regulatory factor-1 (IRF-1) expression

S Giannouli 1, D Tzoanopoulos 1, K Ritis 1, G Kartalis 1, H Moutsopoulos 1, M Voulgarelis 1
PMCID: PMC1754981  PMID: 15082491

Abstract

Background: Patients with myelodysplasia may have autoimmune manifestations (AIM). Interferon regulatory factor-1 (IRF-1) is a transcription factor involved in interferon signalling, leukaemogenesis, and the development of the immune system.

Objectives: To determine whether IRF-1 is implicated in the pathophysiology of AIM in myelodysplasia.

Methods: 14 patients with myelodysplasia were studied, seven with AIM and seven without. Five patients with vasculitis and seven normal subjects served as controls. The expression of IRF-1 was studied in bone marrow mononuclear cells taken from patients and controls, using a relative quantitative reverse transcriptase polymerase chain reaction.

Results: A 10-fold reduction in full length IRF-1 mRNA was detected in the myelodysplasia patients without AIM compared with the normal controls. In contrast, the group with AIM had increased IRF-1 transcripts, to a level almost equal to that observed in patients with vasculitis and normal controls.

Conclusions: Myelodysplasia patients without IRF-1 expression had a decreased incidence of AIM. Thus the absence of IRF-1 transcription factor appears to protect against the development of autoimmunity in myelodysplasia.

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Figure 1 .

Figure 1

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Reverse transcriptase polymerase chain reaction (RT-PCR) amplifications representing interferon regulatory factor-1 (IRF-1) mRNA and 18 S rRNA in patients and controls. (A) Group A, lanes 1–7: seven myelodysplasia patients with autoimmune manifestations. (B) Group B, lanes 1–7: seven myelodysplasia patients without autoimmune manifestations. (C) Group C, lanes 1–5: five patients with systemic vasculitis. (D) Group D, lanes 1–7: seven normal individuals. Myelodysplasia patients from group B have decreased levels of full length IRF-1 mRNA expression in association with exon skipped products, as in case 1 and 4 (arrows). On the other hand, myelodysplasia patients from group A express the full length of IRF-1 mRNA (a 1006 bp product), without exon skipped products. The control groups (C and D) also show expression of the full length of IRF-1 mRNA. M, 100 bp marker (Gibco).

Figure 2 .

Figure 2

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Box plots showing the median, minimum, maximum, and quartile pixel values for each group of patients. The relative interferon regulatory factor-1 (IRF-1) mRNA expression to 18s rRNA levels is presented as box plots with median and interquartile ranges for each group. Group A, seven myelodysplastic patients with autoimmune manifestations; group B, seven myelodysplastic patients without autoimmune manifestations; group C, five patients with systemic vasculitis; group D, seven normal individuals.

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Bennett J. M., Catovsky D., Daniel M. T., Flandrin G., Galton D. A., Gralnick H. R., Sultan C. Proposals for the classification of the myelodysplastic syndromes. Br J Haematol. 1982 Jun;51(2):189–199. [PubMed] [Google Scholar]
  2. Bloch D. A., Michel B. A., Hunder G. G., McShane D. J., Arend W. P., Calabrese L. H., Edworthy S. M., Fauci A. S., Fries J. F., Leavitt R. Y. The American College of Rheumatology 1990 criteria for the classification of vasculitis. Patients and methods. Arthritis Rheum. 1990 Aug;33(8):1068–1073. doi: 10.1002/art.1780330803. [DOI] [PubMed] [Google Scholar]
  3. Greenberg P., Cox C., LeBeau M. M., Fenaux P., Morel P., Sanz G., Sanz M., Vallespi T., Hamblin T., Oscier D. International scoring system for evaluating prognosis in myelodysplastic syndromes. Blood. 1997 Mar 15;89(6):2079–2088. [PubMed] [Google Scholar]
  4. Hamblin T. J. Immunological abnormalities in myelodysplastic syndromes. Semin Hematol. 1996 Apr;33(2):150–162. [PubMed] [Google Scholar]
  5. Harada H., Kondo T., Ogawa S., Tamura T., Kitagawa M., Tanaka N., Lamphier M. S., Hirai H., Taniguchi T. Accelerated exon skipping of IRF-1 mRNA in human myelodysplasia/leukemia; a possible mechanism of tumor suppressor inactivation. Oncogene. 1994 Nov;9(11):3313–3320. [PubMed] [Google Scholar]
  6. Kröger Andrea, Köster Mario, Schroeder Katharina, Hauser Hansjörg, Mueller Peter P. Activities of IRF-1. J Interferon Cytokine Res. 2002 Jan;22(1):5–14. doi: 10.1089/107999002753452610. [DOI] [PubMed] [Google Scholar]
  7. Maruyama M., Fujita T., Taniguchi T. Sequence of a cDNA coding for human IRF-1. Nucleic Acids Res. 1989 Apr 25;17(8):3292–3292. doi: 10.1093/nar/17.8.3292. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Miyamoto M., Fujita T., Kimura Y., Maruyama M., Harada H., Sudo Y., Miyata T., Taniguchi T. Regulated expression of a gene encoding a nuclear factor, IRF-1, that specifically binds to IFN-beta gene regulatory elements. Cell. 1988 Sep 9;54(6):903–913. doi: 10.1016/s0092-8674(88)91307-4. [DOI] [PubMed] [Google Scholar]
  9. Ogasawara K., Hida S., Azimi N., Tagaya Y., Sato T., Yokochi-Fukuda T., Waldmann T. A., Taniguchi T., Taki S. Requirement for IRF-1 in the microenvironment supporting development of natural killer cells. Nature. 1998 Feb 12;391(6668):700–703. doi: 10.1038/35636. [DOI] [PubMed] [Google Scholar]
  10. Salkowski C. A., Kopydlowski K., Blanco J., Cody M. J., McNally R., Vogel S. N. IL-12 is dysregulated in macrophages from IRF-1 and IRF-2 knockout mice. J Immunol. 1999 Aug 1;163(3):1529–1536. [PubMed] [Google Scholar]
  11. Tada Y., Ho A., Matsuyama T., Mak T. W. Reduced incidence and severity of antigen-induced autoimmune diseases in mice lacking interferon regulatory factor-1. J Exp Med. 1997 Jan 20;185(2):231–238. doi: 10.1084/jem.185.2.231. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Tanaka N., Ishihara M., Kitagawa M., Harada H., Kimura T., Matsuyama T., Lamphier M. S., Aizawa S., Mak T. W., Taniguchi T. Cellular commitment to oncogene-induced transformation or apoptosis is dependent on the transcription factor IRF-1. Cell. 1994 Jun 17;77(6):829–839. doi: 10.1016/0092-8674(94)90132-5. [DOI] [PubMed] [Google Scholar]
  13. Tzoanopoulos Dimitrios, Speletas Matthaios, Arvanitidis Konstantinos, Veiopoulou Christina, Kyriaki Sofia, Thyphronitis George, Sideras Paschalis, Kartalis Georgios, Ritis Konstantinos. Low expression of interferon regulatory factor-1 and identification of novel exons skipping in patients with chronic myeloid leukaemia. Br J Haematol. 2002 Oct;119(1):46–53. doi: 10.1046/j.1365-2141.2002.03829.x. [DOI] [PubMed] [Google Scholar]
  14. Willman C. L., Sever C. E., Pallavicini M. G., Harada H., Tanaka N., Slovak M. L., Yamamoto H., Harada K., Meeker T. C., List A. F. Deletion of IRF-1, mapping to chromosome 5q31.1, in human leukemia and preleukemic myelodysplasia. Science. 1993 Feb 12;259(5097):968–971. doi: 10.1126/science.8438156. [DOI] [PubMed] [Google Scholar]

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