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 significance. 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-specific PCR in combination with different isotype-specific 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 Calpha or Cepsilon 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.
