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Multiplexed Fluorescent Immunohistochemical Staining, Imaging, and Analysis in Histological Samples of Lymphoma
Published on: January 9, 2019
Circulating Ki67 positive lymphocytes in multiple myeloma and benign monoclonal gammopathy
A Miguel-Garcia1, E Matutes, F Tarin
1Department of Haematology, Hospital General Universitario, Valencia, Spain.
Insights
Proliferating lymphocytes (Ki67+) are higher in multiple myeloma and MGUS patients compared to controls. This Ki67 expression may indicate aggressive multiple myeloma and distinguish it from MGUS.
Area of Science:
- Immunology
- Hematology
- Oncology
Background:
- Multiple myeloma and monoclonal gammopathy of unknown significance (MGUS) are plasma cell disorders.
- Understanding the role of circulating lymphocytes in these conditions is crucial for diagnosis and prognosis.
Purpose of the Study:
- To quantify and characterize proliferating (Ki67+) lymphocytes in multiple myeloma and MGUS patients.
- To correlate these findings with clinical parameters and disease status.
- To investigate the involvement of B and T cell components in disease progression or control.
Main Methods:
- Analysis of blood lymphocytes from patients with multiple myeloma (n=15), MGUS (n=10), and healthy controls (n=10).
- Utilized sequential double immunoenzymatic staining with antibodies for Ki67, T cell markers (CD3, CD4, CD8), B cell markers (HLA-Dr, immunoglobulin light chains), and NK cell marker (CD11b).
Main Results:
- Significantly higher proportion of Ki67+ lymphocytes in multiple myeloma (6.8%) and MGUS (3.5%) compared to controls (1.69%).
- Over 50% of Ki67+ cells in multiple myeloma and MGUS were activated T lymphocytes (CD3+/HLA-Dr+).
- Elevated levels of proliferating T cells expressing CD8 and CD11b were observed in multiple myeloma and MGUS patients compared to controls. In multiple myeloma, Ki67+ lymphocytes correlated positively with beta-2-microglobulin and disease stage.
Conclusions:
- Ki67 expression in blood lymphocytes may serve as a prognostic indicator for aggressive multiple myeloma.
- Ki67+ lymphocyte analysis could aid in differentiating multiple myeloma from MGUS.
- Activated proliferating T cells might represent an immune response against the tumor in these conditions.
Aims:
To estimate the proportion and nature of the proliferating (Ki67+) circulating lymphocytes in a series of patients with multiple myeloma and monoclonal gammopathy of unknown significance (MGUS) and to correlate this with other clinical and laboratory parameters, using blood from healthy adults as a control. To investigate the extent to which the B and T lymphoid components are involved in progression and/or control of disease.
Methods:
Blood lymphocytes from 15 patients with multiple myeloma, 10 patients with MGUS and 10 healthy adults were analysed using a sequential double immunoenzymatic staining technique. Antibodies directed against Ki67 were used to detect cells in cycle, CD3, CD4, and CD8 to identify T cells, HLA-Dr as a marker for B cells and activated T cells, and CD11b as a marker for natural killer cells. Polyclonal antibodies directed against the kappa and lambda immunoglobulin light chains were also used to detect B cells.
Results:
The proportion of proliferating (Ki67+) lymphocytes was significantly higher in patients with multiple myeloma (6.8 +/- 2.6) and MGUS (3.5 +/- 1.1) compared with the normal controls (1.69 +/- 0.3); this was also true when multiple myeloma and MGUS cases were compared. In multiple myeloma and MGUS over 50% of the Ki67+ cells were activated T lymphocytes (CD3+/HLA-Dr+); a minority (11%) were non-clonal B lymphocytes. In contrast to controls (6.7 +/- 1.9), in patients with multiple myeloma and MGUS the proportion of proliferating T cells expressing CD8 (23.6 +/- 12.5 and 15.3 +/- 7.7, respectively) and CD11b (13 +/- 8.7 and 11.6 +/- 3.9, respectively) was higher. In multiple myeloma there was a positive correlation between the proportion of Ki67+ lymphocytes, beta-2-microglobulin concentrations and disease stage.
Conclusions:
Although the number of patients investigated is small, this study suggests that Ki67 expression in blood lymphocytes from patients with multiple myeloma may be a good prognostic indicator for aggressive disease and may help to distinguish multiple myeloma from MGUS. The activated proliferating T cells in these diseases may represent an immunological reaction against the tumour.
