Abstract
BackgroundInteraction between multiple myeloma (MM) cells and proximal monocytes is expected during plasma cell proliferation. However, the role of monocyte subsets in the disease progression is unknown.ObjectiveThis study evaluated circulating monocyte populations in MM patients and their correlation with disease severity.MethodsPeripheral monocytes from 20 patients with MM attending Assiut University Hospital in Assiut, Egypt, between October 2018 and August 2019 were processed using a flow cytometry procedure and stratified using the intensity of expression of CD14 and CD16 into classical (CD16−CD14++), intermediate (CD16+CD14++), and non-classical (CD16++CD14+) subsets. The data were compared with data from 20 healthy control participants with comparable age and sex.ResultsIn patients with MM, the percentage of classical monocytes was significantly lower (mean ± standard error: 77.24 ± 0.66 vs 83.75 ± 0.5), while those of non-classical (12.44 ± 0.5 vs 8.9 ± 0.34) and intermediate (10.3 ± 0.24 vs 7.4 ± 0.29) monocytes were significantly higher when compared with those of controls (all p < 0.0001). Proportions of non-classical and intermediate monocytes correlated positively with serum levels of plasma cells, M-protein, calcium, creatinine and lactate dehydrogenase, and correlated negatively with the serum albumin level. Proportions of classical monocytes correlated positively with albumin level and negatively correlated with serum levels of M-protein, plasma cells, calcium, creatinine, and lactate dehydrogenase.ConclusionCirculating monocyte subpopulations are skewed towards non-classical and intermediate monocytes in MM patients, and the intensity of this skewness increases with disease severity.
Highlights
Multiple myeloma (MM) is a cancer that affects B-cells, plasma cells, leading to their expansion and the excessive production of immunoglobulins
Circulating non-classical monocytes have been observed to increase in some autoimmune diseases such as lupus and rheumatoid arthritis,[10,11] and the frequency of intermediate monocytes has been associated with bone erosion in patients with psoriatic arthritis.[12]
After comparing the mean levels of serum calcium, lactate dehydrogenase (LDH), and serum creatinine between MM patients and healthy controls, we found statistically significant increased levels in MM patients
Summary
Multiple myeloma (MM) is a cancer that affects B-cells, plasma cells, leading to their expansion and the excessive production of immunoglobulins. Malignant plasma cells may control the quality of the immune cells in the bone marrow and produce immunoglobulins that can act as tumour-associated antigens which are further processed by antigen-presenting cells to stimulate specific anti-tumour T-cell responses.[1] Monocytes and macrophages play a fundamental role in this inflammatory response, possibly through bone marrow expansion and cytokine production in myeloma patients.[2,3,4,5] This is corroborated by findings from in-vitro studies.[6,7] The increased peripheral monocytes in MM patients may inhibit antitumor immune responses and increase tumour aggression.[2,3] Human peripheral blood monocytes are a heterogeneous population, as they differ in their phenotype, surface marker expression, and function.[8] They can be classified based on the fluorescent intensities of CD16 and CD14 into three distinct populations, including classical monocytes (CD16−CD14++), intermediate monocytes (CD16+CD14++), and non-classical monocytes (CD16++CD14+).[9] Circulating non-classical monocytes have been observed to increase in some autoimmune diseases such as lupus and rheumatoid arthritis,[10,11] and the frequency of intermediate monocytes has been associated with bone erosion in patients with psoriatic arthritis.[12]. The role of monocyte subsets in the disease progression is unknown
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