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Defective complement activity in chronic lymphocytic leukemia.

M E Heath, B D Cheson

    American Journal of Hematology
    |May 1, 1985
    PubMed
    Summary
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    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.

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  • 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.