Department of Pathophysiology, Medical School, National University of Athens, Athens, Greece (M. Voulgarelis, S. Giannouli, A. G. Tzioufas); First Division of Internal Medicine, Democritus University of Trace, Alexandroupolis, Greece (K. Ritis).
Myelodysplasia-associated autoimmunity: clinical and pathophysiologic concepts
Article first published online: 7 OCT 2004
European Journal of Clinical Investigation
Volume 34, Issue 10, pages 690–700, October 2004
How to Cite
Voulgarelis, M., Giannouli, S., Ritis, K. and Tzioufas, A. G. (2004), Myelodysplasia-associated autoimmunity: clinical and pathophysiologic concepts. European Journal of Clinical Investigation, 34: 690–700. doi: 10.1111/j.1365-2362.2004.01417.x
- Issue published online: 7 OCT 2004
- Article first published online: 7 OCT 2004
- Received 4 August 2004; accepted 7 September 2004
- autoimmune manifestations;
- bone marrow failure;
- ineffective haemopoiesis;
- myelodysplastic syndrome
Myelodysplastic syndrome (MDS), an acquired clonal disorder of haemopoietic progenitor cells, is characterized by haemopoietic insufficiency associated with cytopenias, leading to serious morbidity plus the additional risk of leukaemic transformation. In MDS an acquired insult to the haemopoietic stem cell leads to impaired differentiation and myelodysplasia. However, there is increasing evidence that the marrow failure of MDS is immune-mediated. A model of MDS pathophysiology suggests that transformation of normal stem cells induces an autoimmune T-cell response with the bone marrow as the target organ. This autoimmune attack results in chronic overproduction of pro-apoptotic cytokines, especially tumour necrosis factor alpha (TNFα). In addition, several reports have revealed that approximately 10% of MDS patients have clinical autoimmune disorders. This review illustrates the cellular/molecular mechanisms and the implication of the tumour suppressor gene interferon regulatory factor-1 (IRF-1) in the pathophysiology of MDS-associated autoimmune deregulation.