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The complement system is defective in chronic lymphatic leukemia patients and in their healthy relatives
M Schlesinger1, I Broman, G Lugassy
1Institute of Immunology, Barzilai Medical Center, Ashkelon, Israel.
Insights
Chronic lymphocytic leukemia (CLL) patients often have impaired complement systems, with low protein levels found in most patients at diagnosis. These complement defects correlate with disease stage and may contribute to infections.
Area of Science:
- Immunology
- Hematology
- Clinical Medicine
Background:
- The complement system is crucial for immune response.
- Infections are common complications in chronic lymphocytic leukemia (CLL).
- The role of the complement system in CLL pathophysiology is not fully understood.
Purpose of the Study:
- To investigate complement system impairment in CLL patients.
- To correlate complement levels with disease stage and infectious complications.
- To explore potential genetic predisposition to complement deficits in CLL.
Main Methods:
- Serum levels of 14 complement proteins were measured using radial immunodiffusion assay.
- 26 CLL patients were monitored over 2 years.
- CLL patients were compared to sex- and age-matched healthy controls.
Main Results:
- 18 of 26 CLL patients exhibited low serum complement levels at diagnosis (P < 0.0001).
- Defects affected classical and/or alternative pathways, including late components (C5-C9).
- Reduced properdin was the most frequent abnormality (11/18); defects were more prevalent in advanced disease stages (Rai II-IV, 100%) than early stages (0-1, 40%).
- Severe infections occurred in 5 patients, predominantly those with complement deficiencies and advanced disease.
Conclusions:
- An impaired complement system is associated with CLL pathophysiology and infectious complications.
- Complement deficits may be linked to disease progression and severity.
- Genetic predisposition could underlie complement deficiency in some CLL patients.
Abstract:
The present study was aimed at analyzing the existence of an impaired complement system in CLL patients. For this purpose, the serum levels of the serum complement proteins C1q, C1r, C1s, C2, C3, C4, C5, C6, C7, C8, C9, Factor B and properdin were repeatedly evaluated by means of radial immunodiffusion assay in 26 CLL patients over a period of 2 years. At the time of diagnosis, 18 of the 26 CLL patients showed low serum levels in at least one of these complement proteins as compared to a group of sex- and age-matched healthy subjects (P < 0.0001). Complement defects affected either the classical and/or the alternative pathway components, and in some case low levels of late components (C5-C9) were also observed. A reduced level of properdin was the most frequent abnormality (11/18). The presence of such abnormalities were correlated with the stage of the disease, and they were found in 100% of the patients (11) in advanced stages (Rai II-IV), and in 40% of patients (15) in early stages (0-1) (P < 0.004). Severe infections occurred in five patients; four of them were in advanced stages of the disease and had decreased levels of at least one complement component, whereas the remaining patient was in an early stage and had normal levels of complement components. These data support the notion that an impaired complement system might be involved in the pathophysiology of CLL and its infectious complications. Although more work is needed to sustain this hypothesis, we discuss the possibility on the basis of data obtained in the first-degree relatives of CLL patients, that in some CLL patients the complement deficit might reflect a genetic predisposition.