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Letters to the Editor |
1 Laboratory Medicine, Immunology, and 2 Internal Medicine, Hematology, University Hospital Leuven, Leuven, Belgium
aAddress correspondence to this author at: Laboratory Medicine, University Hospital Leuven, Herestraat 49, B-3000 Leuven, Belgium. Fax 32-16-347931; e-mail Xavier.bossuyt{at}uz.kuleuven.ac.be.
To the Editor:
Luraschi et al. (1) recently published the first report describing the use of capillary zone electrophoresis (CZE) coupled with immunosubtraction to detect and characterize low concentrations of free 
heavy chains in serum. By contrast, we describe a case in which CZE failed to detect and characterize µ heavy chain disease.
A 90-year-old woman who complained of weight loss presented with progressive enlargement of the left parotid gland, splenomegaly, and palpable inguinal lymph node enlargements. A combined positron emission tomography/computed tomography whole body scan confirmed left parotid involvement as well as supra- and infradiaphragmatic involvement of the lymph nodes. Laboratory investigation showed hemoglobin, leukocyte count and differentiation, and a platelet count within the appropriate reference intervals. Serum lactate dehydrogenase was increased. The IgG concentration was 5.46 g/L, the IgM concentration 1.27 g/L, and the IgA concentration 0.78 g/L. CZE results were normal, but immunofixation revealed a µ heavy chain. A lymph node biopsy showed an extranodal marginal zone B-cell lymphoma of mucosa-associated tissue. The patient was treated with chlorambucil and had an excellent response.
The CZE electropherogram [Paragon 2000 (software version 1.6.02); Beckman-Coulter; Fig. 1
] revealed no anomalous peaks. The -globulin appeared normal. Immunofixation analysis (Sebia system using Hydragel 4 IF gels; Fig. 1
, inset) revealed a µ-type monoclonal component lacking light chains and migrating in the 
2-globulin fraction. Immunosubtraction performed with Sepharose-bound antibodies and the Paragon 2000 instrument failed to demonstrate the µ heavy chain. Pretreatment of the sample with anti-µ did not change the electropherogram. The IgM subtraction pattern as an overlay on the CZE pattern is shown in Fig. 1 of the Data Supplement that accompanies the online version of this letter at http://www.clinchem.org/content/vol51/issue7/. Direct evidence for the occurrence of free µ heavy chains was obtained by following a set of experiments (Fig. 2 of the online Data Supplement). Pretreatment of the sample with anti-µ caused the monoclonal µ heavy chain to disappear on immunofixation analysis. Pretreatment with anti-
or anti-
antibodies led to a decrease in the polyclonal -globulin zone on immunofixation, but not of the monoclonal µ heavy chain, providing evidence for the presence of free µ-type heavy chains. On the basis of the immunofixation analysis and the nephelometric quantification, we estimated the concentration of the monoclonal µ fraction to be 
1.27 g/L. Immunofixation analysis of a 25-fold–concentrated urine sample revealed the presence of free monoclonal µ heavy chains.
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µ Heavy chain disease is the rarest of all heavy chain diseases with only 34 cases reported to date (2)(3). The most common symptoms of patients with µ heavy chain disease are those of lymphoproliferative malignancy (chronic lymphatic leukemia, non-Hodgkin lymphoma, Waldenström macroglobulinemia, and multiple myeloma). Splenomegaly and hepatomegaly are common. There is no specific treatment.
Although the detection of low-concentration monoclonal heavy chains by CZE has been reported (1), the present report demonstrates that some heavy chain diseases are missed by CZE. This result is not surprising as it is well known (a) that CZE may fail to detect small monoclonal proteins (4) and (b) that monoclonal free heavy chains are frequently not detected (in >50% of cases) by routine serum protein electrophoresis (3). CZE may miss this specific monoclonal µ heavy chain because of its low concentration and/or its migration in the 2-globulin region. It is therefore essential to perform immunofixation on all samples (serum and urine) in which there is high clinical suspicion of the presence of a monoclonal protein.
References
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