Clonally related IgA- and IgE-secreting plasma cells in a myeloma patient

Objectives: The purpose of this work was to study the clonal relationship b etween the cells that secrete monoclonal proteins in an IgA/ IgE double mul tiple myeloma patient. Double monoclonal gammopathy is a rare condition in which two types of monoclonal proteins can be found in the serum and/or uri ne of patients with multiple myeloma or gammopathy of undetermined signific ance. The study of the relationship between the cells expressing the differ ent monoclonal proteins may provide insight in the pathogenesis of these di sorders. Methods: The clonal relationship of the two tumoral plasma cell po pulations was examined by immunophenotyping and sequence analysis of the va riable regions of the immunoglobulin heavy chain genes. Both immunoglobulin sequences were isolated from the bone marrow using a polymerase chain reac tion (PCR)-based cloning strategy. Rare isotype-switch variants were detect ed by a myeloma-specific PCR in combination with different isotype-specific primers. An in vitro culture system, based on the activation of the CD40 m olecule on the B cell, was used in order to isolate and expand myeloma-rela ted B cells from peripheral blood that could possibly be regarded as myelom a precursor cells. Results: The variable parts of the immunoglobulin heavy chains linked to either C alpha or CE were exactly the same, including the same somatic mutations. From the in vitro CD40 cultures B cells could be is olated that either expressed IgA or IgE with exactly the same variable immu noglobulin part as the myeloma clone. No pre-switched IgM myeloma-related B cells could be found. Conclusion: Both cell populations in this IgA/IgE my eloma patient shared a common clonal origin. No evidence for a pre-switched IgM precursor myeloma cell was found in this patient.