1. ¹Department of Hematology, University of Leuven, Leuven, Belgium
2. ²Stem Cell Institute, University of Leuven, Leuven, Belgium
3. ³Department of Immunology, University of Leuven, Leuven, Belgium
4. ⁴PanGenetics BV, Utrecht, The Netherlands
5. ⁵Department of Hematology, Sint-Augustinus Hospital, Wilrijk, Belgium
6. ⁶Department of Hematology, Jules Bordet Institute, Brussels, Belgium

Correspondence: Dr S Meers, Hematology Department, University Hospital of Leuven, University of Leuven, Herestraat 49, B-3000 Leuven, Belgium. E-mail: stef.meers@med.kuleuven.be

Received 2 July 2007; Revised 6 August 2007; Accepted 8 August 2007; Published online 6 September 2007.

Abstract

Immune mechanisms have been shown to contribute to the process of myelodysplastic syndromes (MDS)-related bone marrow (BM) failure. The aim of this study was to evaluate the possible contribution of activated monocytes through CD40–CD40L(CD154) interactions with activated T helper cells. We demonstrated in 77 predominantly lower risk MDS patients that the CD40 receptor was expressed significantly higher on monocytes and that CD40L was expressed significantly higher on T helper cells in peripheral blood (PB) and BM. Increased levels of CD40 and CD40L were detected in the same patients. In addition, stimulation of the CD40 receptor on purified PB monocytes led to a significantly higher tumor necrosis factor alpha production in patients. Co-culture of BM mononuclear cells of 21 patients in the presence of a blocking CD40 monoclonal antibody (ch5D12) led to a significant increase in the number of colony-forming units. A correlation was seen between increased CD40 expression on monocytes with patients' age below 60 years and with the cytogenetic abnormality trisomy 8. These results demonstrate that CD40 expression on monocytes may identify a subgroup of MDS patients in whom immune-mediated hematopoietic failure is part of the disease process. As such, the CD40–CD40L-based activation of monocytes might be a target to counteract MDS-related BM failure.