Case Report Clonally related IgA- and IgE-secreting plasma cells in a myeloma patient Bakkus MHC, Schots R, Gomez La Fuente PB, Van Riet I, Thielemans K, De Waele M, Van Camp B. Clonally related IgA- and IgE-secreting plasma cells in a myeloma patient. Eur J Haematol 2000: 65: 348±355. # Munksgaard 2000. Abstract: Objectives: The purpose of this work was to study the clonal relationship between the cells that secrete monoclonal proteins in an IgA/ IgE double multiple myeloma patient. Double monoclonal gammopathy is a rare condition in which two types of monoclonal proteins can be found in the serum and/or urine of patients with multiple myeloma or gammopathy of undetermined signi®cance. The study of the relationship between the cells expressing the different monoclonal proteins may provide insight in the pathogenesis of these disorders. Methods: The clonal relationship of the two tumoral plasma cell populations was examined by immunophenotyping and sequence analysis of the variable regions of the immunoglobulin heavy chain genes. Both immunoglobulin sequences were isolated from the bone marrow using a polymerase chain reaction (PCR)-based cloning strategy. Rare isotype-switch variants were detected by a myeloma-speci®c PCR in combination with different isotype-speci®c primers. An in vitro culture system, based on the activation of the CD40 molecule on the B cell, was used in order to isolate and expand myeloma-related B cells from peripheral blood that could possibly be regarded as myeloma precursor cells. Results: The variable parts of the immunoglobulin heavy chains linked to either Ca or Ce were exactly the same, including the same somatic mutations. From the in vitro CD40 cultures B cells could be isolated that either expressed IgA or IgE with exactly the same variable immunoglobulin part as the myeloma clone. No pre-switched IgM myeloma-related B cells could be found. Conclusion: Both cell populations in this IgA/IgE myeloma patient shared a common clonal origin. No evidence for a pre-switched IgM precursor myeloma cell was found in this patient. M. H. C. Bakkus 1 , R. Schots 1 , P. B. Gomez La Fuente 1 , I. Van Riet 1 , K. Thielemans 2 , M. De Waele 1 , B. Van Camp 1 1 Department of Hematology and Immunology and 2 Department of Physiology, VUB, Brussels, Belgium Key words: multiple myeloma; double monoclonal gammopathies; immunoglobulin sequences; polymerase chain reaction Correspondence: Dr M. H. C. Bakkus, Department of Hematology±Immunology, AZ-VUB, Laarbeeklaan 103, 1090 Brussels, Belgium Tel: +31-2-4774564 Fax: +31-2-4774568 e-mail: mbakkus@heim.vub.ac.be Accepted for publication 2 August 2000 Double monoclonal gammopathy (DMG) is a rare condition in which two monoclonal proteins can be found in the serum and/or urine of patients with multiple myeloma (MM) or gammopathy of unde- termined signi®cance (MGUS) (1±3). The incidence of DMG among patients with myeloma is about 1%. The most frequent association is IgG+IgA (32.6%), followed by IgG+IgM (24.1%), two IgG's (17.0%), IgA+IgM (8.5%) and two IgM's (7.8%) (4, 5). The least frequent is IgA+IgE, which has been reported in only one case of MG so far (2). The study of the clonal relationship between the cells that secrete both monoclonal proteins may provide insight into the pathogenesis of these disorders. Immunoglobulin sequence analysis in MM sugg- ested that the oncogenic transformation occurs at the stage of a mature antigen-selected B cell that has passed through the germinal centre reaction and in which the somatic mutation process has stopped (6). In DMG, nucleotide sequence analyses of the Eur J Haematol 2000: 65: 348±355 Printed in UK. All rights reserved Copyright # Munksgaard EUROPEAN JOURNAL OF HAEMATOLOGY ISSN 0902-4441 348