Prevention of CMV-induced myelosuppression by anti-CMV antibodies: an in vitro model
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Published on: May 27, 2011
D Bron1, L Lagneaux, A Delforge
1Institut Jules Bordet, Brussels, Belgium.
Abstract:
Pathogenesis of cytomegalovirus (CMV)-induced myelosuppression is not clearly understood and could be related to a direct toxic effect on the marrow progenitors and/or an alteration of the marrow environment. Myeloid progenitors (granulocyte-macrophage colony-forming units, CFU-GM) were not affected by incubation with increasing titers of CMV (10-10(5) plaque-forming units [pfu]/ml) during 2-6 h. By contrast, using the blast colony-forming cell (Bl-CFC) assay, we confirmed that CMV induced myelosuppression through an alteration of the marrow-derived stromal layer. Using this experimental model, we compared the capacity of nonspecific human immunoglobulins (IgG), specific polyclonal anti-CMV IgG, and a human monoclonal anti-CMV IgG to prevent the myelosuppressive effect of 10(4) pfu/ml of CMV. Specific anti-CMV IgG (polyclonal or monoclonal) at the concentration of 10 micrograms/ml were able to prevent the CMV-induced myelosuppressive effect, whereas nonspecific human IgG was not effective in this model. Our results suggest that 1) CMV-induced myelosuppression is related to an alteration of the marrow microenvironment, 2) specific monoclonal and polyclonal anti-CMV IgG prevent this myelosuppressive effect in vitro, and 3) human monoclonal anti-CMV IgG could be useful in vivo in the immunoprophylaxis of CMV infections.
Insights
Cytomegalovirus (CMV) causes myelosuppression by altering the bone marrow environment, not directly harming progenitors. Specific anti-CMV antibodies, including monoclonal versions, can prevent this effect in vitro.
Area of Science:
- Hematology
- Virology
- Immunology
Background:
- The exact mechanism of cytomegalovirus (CMV)-induced myelosuppression remains unclear.
- It may involve direct toxicity to bone marrow progenitors or changes in the bone marrow microenvironment.
Purpose of the Study:
- To investigate the pathogenesis of CMV-induced myelosuppression.
- To evaluate the efficacy of specific anti-CMV immunoglobulins in preventing this effect.
Main Methods:
- Assessing the effect of CMV on myeloid progenitors (CFU-GM) and blast colony-forming cells (Bl-CFC).
- Utilizing a bone marrow stromal layer model to study CMV-induced myelosuppression.
- Comparing the protective effects of nonspecific IgG, polyclonal anti-CMV IgG, and monoclonal anti-CMV IgG against CMV.
Main Results:
- CMV did not directly affect myeloid progenitors (CFU-GM) at tested concentrations.
- CMV induced myelosuppression by altering the bone marrow stromal layer.
- Specific polyclonal and monoclonal anti-CMV IgG (10 µg/ml) prevented CMV-induced myelosuppression, while nonspecific IgG did not.
Conclusions:
- CMV-induced myelosuppression is primarily mediated by alterations to the bone marrow microenvironment.
- Specific anti-CMV IgG, both polyclonal and monoclonal, demonstrate in vitro efficacy in preventing CMV-induced myelosuppression.
- Human monoclonal anti-CMV IgG shows potential for in vivo immunoprophylaxis against CMV infections.
