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Published on: October 19, 2014
Monocyte dysfunction in patients with multiple myeloma and lymphoplasmacytic disorders is related to serum
C J Mainwaring1, M A Williams, C R Singer
1Department of Haematology, Royal United Hospital NHS Trust, Bath.
Abstract:
We have investigated monocyte function in 30 patients with lymphoplasmacytic disorders and in 21 age and sex matched normal controls. Marked abnormalities of all facets of monocyte function were demonstrated in six patients with multiple myeloma (MM) and a single patient with Waldenström's macroglobulinaemia (WM) plus significant paraproteinaemia. Serious infection occurred in three of these patients. An inverse relationship between the level of the serum paraprotein and impairment of monocyte phagocytosis plus killing of Candida albicans was observed. Crossover studies suggested that these abnormal findings were constitutive and not reversed by removal of the serum paraprotein. The data suggest that monocyte function is constitutively abnormal in patients with MM and can be further, but reversibly, inhibited by high paraprotein levels. Further research is required to confirm these findings, ascertain whether monocyte function can be normalized using chemotherapy or growth factors, and if so, whether their tumouricidal functions could be harnessed in the treatment of this currently incurable condition.
Insights
Monocyte function is impaired in multiple myeloma (MM) and Waldenström's macroglobulinaemia (WM), increasing infection risk. High paraprotein levels worsen this impairment, suggesting a target for future therapies.
Area of Science:
- Immunology
- Hematology
- Oncology
Background:
- Monocyte dysfunction is implicated in lymphoplasmacytic disorders.
- The impact of paraproteins on monocyte function requires further elucidation.
Purpose of the Study:
- To investigate monocyte function in patients with lymphoplasmacytic disorders.
- To determine the relationship between paraprotein levels and monocyte function.
Main Methods:
- Assessed monocyte phagocytosis and candidacidal activity in patients and controls.
- Correlated monocyte function with serum paraprotein levels.
- Performed crossover studies to assess reversibility of abnormalities.
Main Results:
- Marked monocyte function abnormalities observed in multiple myeloma (MM) and Waldenström's macroglobulinaemia (WM) patients.
- Inverse relationship between paraprotein level and monocyte phagocytosis/killing capacity.
- Abnormalities were largely constitutive but exacerbated by high paraprotein levels.
Conclusions:
- Monocyte function is constitutively impaired in MM and further inhibited by paraproteins.
- Potential for therapeutic interventions targeting monocyte function in MM and WM.
- Further research needed to explore normalization with chemotherapy or growth factors.
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