Comparison of serum immunofixation electrophoresis and free light chain assays in the detection of monoclonal gammopathies.

BACKGROUND: Diagnosis of monoclonal gammopathies (MGs) is determined by demonstration of a monoclonal immunoglobulin molecule or chain in serum and/or urine. Previous results on immunofixation electrophoresis (IFE) and quantitative free light chain (FLC) measurements have been conflicting. PATIENTS AND METHODS: The purpose of this study was to compare IFE with serum FLC assays in the detection of MG. Between November 2006 and November 2007, results on routinely ordered serum IFE specimens were compared with independently conducted FLC assays. RESULTS: Monoclonal gammopathies were identified in 144 specimens by IFE; 73 patients (50.7%) had a normal kappa/lambda ratio in the FLC assay. Also, 44.6% of samples with IgG and IgA M-proteins had a normal kappa/lambda ratio. Of 357 sera that showed no M-protein by IFE, 95.8% exhibited a normal kappa/lambda ratio. Out of 11 patients with light chain disease, 9 had abnormal kappa/lambda ratios. It is unclear why half of the patients with MG by IFE had normal kappa/lambda ratios. Lower M-components in these patients suggested that some had monoclonal gammopathy of undetermined significance. CONCLUSION: For screening purposes, serum IFE should be carried out in patients with suspected MG.

Human monoclonal macroglobulins with antibody activity.

Assays for specific antigen-binding activity were performed on sera from 172 patients with monoclonal macroglobulinemia defined by immunofixation electrophoresis. The sera were collected between 1970 and 2002. Mean IgM level was 1,409 mg/dL with a range from 70 to 6,800. Cryoglobulins were identified in 15.3% (26/170 sera: 12 trace, five single component, and nine mixed IgM-IgG). Rheumatoid factor (RF) was detected in 19 of 151 (12.6%) samples with titers ranging from 1:80 to 1:327,680. Among the nine mixed IgM-IgG cryos, eight were RF-positive and six of six displayed positivity for hepatitis C virus. Cold agglutinins (CA) were present in 8.5% (10/117) of sera with anti-I titers between 1:512 and 1:65,536. IgM binding to a series of glycosaminoglycan oligosaccharides, glycolipids, and glycoprotein antigens was found in 75 samples (43%). IgM binding to antigens having known associations to polyneuropathies occurred in 20 patients (12%). Antinuclear antibody (ANA) was documented in 10.7% (18/169) of sera. Anti-DNA activity was absent in all samples tested. Sera from 71% of patients with monoclonal macroglobulinemia in this series exhibited binding to autoantigens. Some of these immune complexes resulted in clinically significant manifestations. Our results suggest that many monoclonal immunoglobulins may be functional antibodies rather than "paraproteins." Characterization of antigen-binding activities may provide insight into the pathogenesis of monoclonal gammopathies.