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Phagocytes and C4 in paraproteinaemia
Abstract:
Immunological studies were performed on patients with multiple myeloma. A defect in polymorphonuclear leucocyte (PMN) function as evidenced by diminished adherence of these cells to nylon fibre columns was detected in 16, and low levels of the fourth component of complement (C4) were observed in 14, of the 26 patients studied. Twelve of the patients with low C4 exhibited the defect in PMN adhesiveness whereas only four of the 12 patients with normal C4 showed the defect. The PMN defect was not caused solely by the low C4, since PMNs from seven patients with hereditary angioedema, which is associated with low levels of C4, did not show the defect. The low C4 and defect in PMN adhesiveness occurred primarily in patients with IgG myeloma; all but one of the patients with IgA myeloma, macroglobulinaemia, or light chain disease were normal in both parameters. Results of skin window studies indicated that patients with the PMN defect also had a defect in the early PMN inflammatory response. The defect in PMN adhesiveness could be completely corrected by incubating the cells in normal plasma. Binding of the C4 to paraprotein could not be demonstrated, and C1 activation was found to be caused only by one of 10 isolated paraproteins studied. These studies indicate that patients with paraproteinaemia have immunological abnormalities in addition to low immunoglobulin levels and suggest that these abnormalities may be involved in the pathogenesis of the recurrent infections commonly associated with this disease.
Insights
Patients with multiple myeloma often have immune system defects, including impaired polymorphonuclear leucocyte (PMN) function and low complement C4 levels, contributing to recurrent infections.
Area of Science:
- Immunology
- Hematology
- Clinical Medicine
Background:
- Multiple myeloma is associated with immune dysregulation and increased susceptibility to infections.
- Polymorphonuclear leucocyte (PMN) dysfunction and complement component deficiencies, particularly C4, are observed in some patients.
Purpose of the Study:
- To investigate immunological abnormalities in multiple myeloma patients.
- To determine the relationship between PMN function, C4 levels, and paraprotein type.
- To explore the impact of these defects on the inflammatory response and infection susceptibility.
Main Methods:
- Assessed PMN adherence to nylon fiber columns.
- Measured serum C4 levels.
- Performed skin window studies to evaluate inflammatory response.
- Incubated patient PMNs in normal plasma for functional correction.
- Investigated C4 binding to paraproteins and C1 activation.
Main Results:
- 16 of 26 patients showed defective PMN adherence; 14 had low C4 levels.
- Low C4 was more frequent in patients with defective PMN adherence.
- PMN defects were primarily seen in IgG myeloma patients.
- Skin window studies confirmed impaired early inflammatory response in patients with PMN defects.
- PMN adhesiveness defects were correctable with normal plasma.
Conclusions:
- Multiple myeloma patients exhibit immunological abnormalities beyond immunoglobulin deficiencies.
- Defective PMN function and low C4 levels are common in IgG myeloma and may contribute to infection risk.
- These immune defects may play a role in the pathogenesis of recurrent infections in paraproteinemia.