Elsevier

Seminars in Oncology

Volume 30, Issue 2, April 2003, Pages 318-324
Seminars in Oncology

Waldenstrom's Macroglobulinemia
Human monoclonal macroglobulins with antibody activity,☆☆,

https://doi.org/10.1053/sonc.2003.50077Get rights and content

Abstract

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. Semin Oncol 30:318-324. © 2003 Elsevier Inc. All rights reserved.

Section snippets

Materials and methods

Analysis was carried out on sera from 172 patients with monoclonal macroglobulinemia collected between 1970 to 2002 (12 from 1970 to 1979, 17 from 1980 to 1989, 53 from 1990 to 1995, 75 from 1996 to 2000, nine in 2001, and six in 2002). Sera were stored at −20°C until 1 to 20 days before assay. Clinical data were determined by retrospective chart review. The study protocol was approved by the Institutional Review Board, Baylor University Medical Center, Dallas, TX.

Results

Mean age of the patients was 67 years (range, 31 to 96). There were 90 men and 82 women. Of the original 172 patient sera, one could not be verified as containing monoclonal macroglobulin and was excluded. The remaining 171 had monoclonal macroglobulins by IFE. Quantitative serum IgM levels varied between 70 and 6,800 mg/dL, with a mean level of 1,409. Some patients did not have a definable M-protein on SPE because of polyclonal hypergammaglobulinemia or low serum IgM levels. Biclonal

Discussion

The presence of antibody activity in serum from a patient with monoclonal gammopathy does not necessarily indicate that the M-protein possesses the activity. Criteria to establish that monoclonal immunoglobulins are antibodies have been discussed.1, 5, 6, 7, 8, 9, 10, 11 That some monoclonal macroglobulins and myeloma proteins satisfy these criteria has been documented for more than three decades. Most of the antigens identified have been of autologous or bacterial origin (Table 4).1, 24, 25, 26

Acknowledgements

We thank Drs Rana Saad and George Netto for performing the hepatitis C RNA determinations.

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    Supported in part by the Edward and Ruth Wilkof Foundation, the Robert Schanbaum Memorial Fund, and the James E. Nauss Cancer Research Fund.

    ☆☆

    Address reprint requests to Marvin J. Stone, MD, Baylor-Sammons Cancer Center, 3500 Gaston Ave, Dallas, TX 75246.

    0093-7754/03/3002-0042$30.00/0

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