Contributions
Abstract: PB1844
Type: Publication Only
Background
Recent data indicate a significant role of antigenic stimulation in chronic lymphocytic leukemia (CLL) development. It has been suggested that severe, symptomatic infections of bacterial and viral etiology can initiate immune disorders leading to the development of CLL. A special role is attributed to infections of the respiratory tract of bacterial etiology, especially those with Streptococcus pneumoniae. The induction of a humoral response against the pneumococcal sheath of antigens depends on the B-cell receptor (B-cell receptor) and receptors recognizing pathogen-associated molecular patterns (PAMPs), which also include Toll-like receptors (TLRs), especially TLR4 signaling pathway with the synergistic effect of ligands for TLR2 derived from the cell wall of the pathogens and TLR9, which recognizes fragments of nucleic acids.
Aims
The aim of the study was to evaluate the relationship between the expression of TLR2 and TLR9 responsible for the recognition of Streptococcus pneumoniae antigens and prognostic factors, treatment free survival (TFS) and the incidence of infectious complications in patients with CLL.
Methods
The study group consisted of 119 patients aged 49-87 with newly diagnosed CLL. Expression of the studied receptors was assessed by flow cytometry on CD19+ lymphocytes B and CD14+ monocytes with the use of monoclonal antibodies: FITC antihuman CD282 (TLR2) and PE Rat anti-Human CD289 (TLR9).
Results
In patients with CLL percentages of B lymphocytes expressing TLR2 and TLR9 were significantly lower compared to the control group (Md 0.38% vs. 1.58%, p <0.05) and Md 0.6% vs. 16.84%; p <0.01, respectively). The lower percentage of CD19+/TLR2+ and CD19+/ TLR9+ cells was associated with unfavorable prognostic factors (deletion of 17p and/or deletion of 11q, ZAP-70 and CD38 expression). Percentages of CD14+/TLR9+ monocytes were lower in the group of patients with advanced disease stages according to the Rai classification, CD38 and ZAP-70 expression and unfavorable cytogenetic aberrations. Percentages of CD14+/TLR2+ cells were lower in CD38-positive and ZAP-70-positive patients. There was also a significantly lower percentage of CD19+/TLR9+ B cells and CD14+/TLR9+ monocytes in patients requiring treatment during observation in comparison with the group of patients with no need to start the therapy. TFS was significantly longer in patients with a higher percentage of monocytes expressing TLR9 (25 vs 20 months, p <0.05).
The percentage of B lymphocytes expressing TLR9 was significantly lower in patients with recurrent infections. In addition, the reverse correlation between the percentage of monocytes expressing TLR2 and TLR9 and the overall incidence of infections and the incidence of the bacterial infections was observed. Moreover, in patients who required IgG supplementation, the percentages of monocytes CD14+/TLR9+ and lymphocytes CD19+/TLR9+ were significantly lower compared to the patients without the need for supplementation (p <0.05).
Conclusion
The presented data suggest that the reduced expression of TLR2 and TLR9 might be involved in CLL pathogenesis and progression. One of the potential mechanisms in which the aberrant expression of TLR2 and TLR9 may affect the development and progression of CLL is the increasing susceptibility to infections that from one side are one of the most important causes of morbidity and mortality in patients with CLL, and on the other side may contribute to the progression of leukemia.
Session topic: 5. Chronic lymphocytic leukemia and related disorders – Biology & Translational Research
Keyword(s): Chronic Lymphocytic Leukemia, Infection, Prognostic factor
Abstract: PB1844
Type: Publication Only
Background
Recent data indicate a significant role of antigenic stimulation in chronic lymphocytic leukemia (CLL) development. It has been suggested that severe, symptomatic infections of bacterial and viral etiology can initiate immune disorders leading to the development of CLL. A special role is attributed to infections of the respiratory tract of bacterial etiology, especially those with Streptococcus pneumoniae. The induction of a humoral response against the pneumococcal sheath of antigens depends on the B-cell receptor (B-cell receptor) and receptors recognizing pathogen-associated molecular patterns (PAMPs), which also include Toll-like receptors (TLRs), especially TLR4 signaling pathway with the synergistic effect of ligands for TLR2 derived from the cell wall of the pathogens and TLR9, which recognizes fragments of nucleic acids.
Aims
The aim of the study was to evaluate the relationship between the expression of TLR2 and TLR9 responsible for the recognition of Streptococcus pneumoniae antigens and prognostic factors, treatment free survival (TFS) and the incidence of infectious complications in patients with CLL.
Methods
The study group consisted of 119 patients aged 49-87 with newly diagnosed CLL. Expression of the studied receptors was assessed by flow cytometry on CD19+ lymphocytes B and CD14+ monocytes with the use of monoclonal antibodies: FITC antihuman CD282 (TLR2) and PE Rat anti-Human CD289 (TLR9).
Results
In patients with CLL percentages of B lymphocytes expressing TLR2 and TLR9 were significantly lower compared to the control group (Md 0.38% vs. 1.58%, p <0.05) and Md 0.6% vs. 16.84%; p <0.01, respectively). The lower percentage of CD19+/TLR2+ and CD19+/ TLR9+ cells was associated with unfavorable prognostic factors (deletion of 17p and/or deletion of 11q, ZAP-70 and CD38 expression). Percentages of CD14+/TLR9+ monocytes were lower in the group of patients with advanced disease stages according to the Rai classification, CD38 and ZAP-70 expression and unfavorable cytogenetic aberrations. Percentages of CD14+/TLR2+ cells were lower in CD38-positive and ZAP-70-positive patients. There was also a significantly lower percentage of CD19+/TLR9+ B cells and CD14+/TLR9+ monocytes in patients requiring treatment during observation in comparison with the group of patients with no need to start the therapy. TFS was significantly longer in patients with a higher percentage of monocytes expressing TLR9 (25 vs 20 months, p <0.05).
The percentage of B lymphocytes expressing TLR9 was significantly lower in patients with recurrent infections. In addition, the reverse correlation between the percentage of monocytes expressing TLR2 and TLR9 and the overall incidence of infections and the incidence of the bacterial infections was observed. Moreover, in patients who required IgG supplementation, the percentages of monocytes CD14+/TLR9+ and lymphocytes CD19+/TLR9+ were significantly lower compared to the patients without the need for supplementation (p <0.05).
Conclusion
The presented data suggest that the reduced expression of TLR2 and TLR9 might be involved in CLL pathogenesis and progression. One of the potential mechanisms in which the aberrant expression of TLR2 and TLR9 may affect the development and progression of CLL is the increasing susceptibility to infections that from one side are one of the most important causes of morbidity and mortality in patients with CLL, and on the other side may contribute to the progression of leukemia.
Session topic: 5. Chronic lymphocytic leukemia and related disorders – Biology & Translational Research
Keyword(s): Chronic Lymphocytic Leukemia, Infection, Prognostic factor