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Updated: Aug 19, 2026
From a 2DE-Gel Spot to Protein Function: Lesson Learned From HS1 in Chronic Lymphocytic Leukemia
Published on: October 19, 2014
Defective complement activity in chronic lymphocytic leukemia
Insights
Patients with chronic lymphocytic leukemia (CLL) exhibit impaired C3b binding to bacteria, increasing infection risk. This complement defect may explain susceptibility to bacterial infections in CLL patients.
Area of Science:
- Immunology
- Hematology
- Microbiology
Background:
- Patients with chronic lymphocytic leukemia (CLL) face heightened risks of bacterial infections.
- Complement-mediated opsonization is crucial for clearing encapsulated bacteria, a common pathogen in CLL.
- A potential defect in C3b binding to bacteria in CLL patients warrants investigation.
Purpose of the Study:
- To investigate the C3b binding capacity of serum from CLL patients to various bacterial species.
- To determine if a deficiency in C3b binding contributes to the increased infection susceptibility in CLL.
Main Methods:
- Bacterial strains (Streptococcus pneumoniae types 3, 14, 25; Staphylococcus aureus; Escherichia coli) were incubated with normal serum or CLL patient serum.
- Bound C3b was quantified using spectrophotofluorometry.
- CLL serum was analyzed for potential deficiencies in C3b binding activity, including comparisons with hypogammaglobulinemic CLL patients and those with a history of infection.
Main Results:
- All 15 CLL sera demonstrated reduced C3b binding to at least one bacterial species compared to normal serum.
- C3b binding defects were observed across different bacterial types, irrespective of their complement pathway activation (classical, alternative, or both).
- Restoration of C3b binding upon mixing CLL serum with normal serum indicated a deficiency, not an inhibitor, and was more pronounced in hypogammaglobulinemic CLL patients and those with prior infections.
Conclusions:
- CLL patients possess a functional defect in C3b binding to bacteria, impacting complement-mediated opsonization.
- This impaired C3b binding is a significant factor contributing to the increased incidence of bacterial infections in individuals with CLL.
- Therapeutic strategies aimed at enhancing complement function may be beneficial for managing infections in CLL patients.
Abstract:
Patients with chronic lymphocytic leukemia (CLL) are at an increased risk for infections with bacteria which require complement for osponization. We explored the possibility that patients with CLL have a defect in binding the potent opsonin C3b to bacteria. Bacteria selected for these experiments included Streptococcus pneumoniae type 3, which binds C3 by activating the classical complement pathway (CCP), type 25, which can bind normal amounts of C3b by the alternative complement pathway (ACP), type 14, which can activate both the CCP and ACP, and Staphylococcus aureus and Escherichia coli, both of which activate the CCP. Bacteria were treated with normal serum or serum from 15 patients with CLL, and the bound C3b was quantified spectrophotofluorometrically. Despite normal serum concentrations of C3, C4, Factor B, C-reactive protein, and total hemolytic complement activity, all 15 CLL sera bound reduced amounts of C3b to at least one bacterial species; 9 to S pneumoniae type 3, 8 to types 14 and 25, 11 to S aureus, and 13 to E coli. Mixing normal serum with CLL serum restored C3b binding to all bacteria, suggesting a deficiency rather than an inhibitor of activity. Serum from ten hypogammaglobulinemic CLL patients bound less C3b (62.7 +/- 5% of normal) (means +/- SEM) than those with normal immunoglobulin levels (81.9 +/- 5%) (p less than .005). Nevertheless, the addition of specific antibacterial antibodies to CLL serum did not enhance C3b binding to any of the bacteria. Serum from patients with a history of a bacterial infection bound less C3b (62.3 +/- 5%) than those without a history of infections (76.1 +/- 6%) (p less than .05). Thus, there is a defect in either the activation or activity of C3 in CLL serum which may contribute to the increased incidence of infections in these patients.
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