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Immunoglobulin Gene Sequence Analysis In Chronic Lymphocytic Leukemia: From Patient Material To Sequence Interpretation
Published on: November 26, 2018
[Immune Reconstitution after BTKi Treatment in Chronic Lymphocytic Leukemia]
Yuan-Li Wang1, Pei-Xia Tang1, Kai-Li Chen1
1Department of Hematology, Union Hospital, Fujian Medical University, Fujian Institute of Hematology, Fuzhou 350000, Fujian Province, China.
Insights
Bruton's tyrosine kinase inhibitors (BTKi) treatment effectively reduces chronic lymphocytic leukemia (CLL) clones and enhances immune function by increasing IgA, T cells, and cytokine regulation. BTKi therapy also restores T-cell receptor (TCR) and B-cell receptor (BCR) diversity in CLL patients.
Area of Science:
- Hematology
- Immunology
- Oncology
Context:
- Chronic lymphocytic leukemia (CLL) is a B-cell malignancy characterized by the accumulation of malignant B lymphocytes.
- BTK inhibitors (BTKi) have emerged as a targeted therapy for CLL, offering a more precise approach than traditional chemotherapy.
- Understanding the impact of BTKi on immune reconstitution is crucial for managing long-term outcomes and potential complications in CLL patients.
Purpose:
- To investigate the effects of Bruton's tyrosine kinase inhibitor (BTKi) treatment on immune reconstitution in patients diagnosed with chronic lymphocytic leukemia (CLL).
- To analyze changes in B-cell and T-cell subpopulations, immunoglobulin levels, and cytokine profiles following BTKi therapy in CLL.
Summary:
- Retrospective analysis of 59 CLL patients treated with BTKi revealed significant reduction in malignant B-cell clones (CD5+/CD19+) within one year.
- BTKi treatment led to increased IgA levels, altered T-cell subpopulations (increased CD4+ and CD8+ cells), and modulated cytokine expression (upregulated IL-2, downregulated IL-4 and IFN-γ).
- Importantly, BTKi therapy promoted the recovery of T-cell receptor (TCR) and B-cell receptor (BCR) diversity, particularly in patients achieving complete remission.
Impact:
- BTKi treatment demonstrates a multifaceted role in immune reconstitution for CLL patients, extending beyond direct tumor cell reduction.
- The observed restoration of immune cell populations and diversity suggests a potential for improved long-term immune surveillance and reduced susceptibility to infections.
- These findings highlight BTKi as a valuable therapeutic strategy that not only targets CLL but also contributes to the recovery of the patient's overall immune function.
Objective:
To analyze the immune reconstitution after BTKi treatment in patients with chronic lymphocytic leukemia (CLL).
Methods:
The clinical and laboratorial data of 59 CLL patients admitted from January 2017 to March 2022 in Fujian Medical University Union Hospital were collected and analyzed retrospectively.
Results:
The median age of 59 CLL patients was 60.5(36-78). After one year of BTKi treatment, the CLL clones (CD5 +/CD19 +) of 51 cases (86.4%) were significantly reduced, in which the number of cloned-B cells decreased significantly from (46±6.1)×109/L to (2.3±0.4)×109/L (P =0.0013). But there was no significant change in the number of non-cloned B cells (CD19 + minus CD5 +/CD19 +). After BTKi treatment, IgA increased significantly from (0.75±0.09)g/L to (1.31±0.1)g/L (P <0.001), while IgG and IgM decreased from (8.1±0.2)g/L and (0.52±0.6)g/L to (7.1±0.1)g/L and (0.47±0.1)g/L, respectively (P <0.001, P =0.002). BTKi treatment resulted in a significant change in T cell subpopulation of CLL patients, which manifested as both a decrease in total number of T cells from (2.1±0.1)×109/L to (1.6±0.4)×109/L and NK/T cells from (0.11±0.1)×109/L to (0.07±0.01)×109/L (P =0.042, P =0.038), both an increase in number of CD4 + cells from (0.15±6.1)×109/L to (0.19±0.4)×109/L and CD8 + cells from (0.27±0.01)×109/L to (0.41±0.08)×109/L (both P <0.001). BTKi treatment also up-regulated the expression of interleukin (IL)-2 while down-regulated IL-4 and interferon (IFN)-γ. However, the expression of IL-6, IL-10, and tumor necrosis factor (TNF)-α did not change significantly. BTKi treatment could also restored the diversity of TCR and BCR in CLL patients, especially obviously in those patients with complete remission (CR) than those with partial remission (PR). Before and after BTKi treatment, Shannon index of TCR in patients with CR was 0.02±0.008 and 0.14±0.001 (P <0.001), while in patients with PR was 0.01±0.03 and 0.05±0.02 (P >0.05), respectively. Shannon index of BCR in patients with CR was 0.19±0.003 and 0.33±0.15 (P <0.001), while in patients with PR was 0.15±0.009 and 0.23±0.18 (P <0.05), respectively.
Conclusions:
BTKi treatment can shrink the clone size in CLL patients, promote the expression of IgA, increase the number of functional T cells, and regulate the secretion of cytokines such as IL-2, IL-4, and IFN-γ. BTKi also promote the recovery of diversity of TCR and BCR. BTKi treatment contributes to the reconstitution of immune function in CLL patients.
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