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

• Published in: European journal of haematology Vol. 65; no. 5; pp. 348 - 355
• Main Authors: Bakkus, M. H. C., Schots, R., Gomez La Fuente, P. B., Van Riet, I., Thielemans, K., De Waele, M., Van Camp, B.
• Format: Journal Article
• Language: English
• Published: Copenhagen Munksgaard International Publishers 01.11.2000; Blackwell
• Subjects: Aged; Aged, 80 and over; B-Lymphocytes - cytology; B-Lymphocytes - immunology; Base Sequence; Biological and medical sciences; CD40 Ligand; Clone Cells - metabolism; Culture Media; double monoclonal gammopathies; Humans; Immunodeficiencies. Immunoglobulinopathies; Immunoglobulin A - blood; Immunoglobulin E - blood; Immunoglobulin Heavy Chains - genetics; immunoglobulin sequences; Immunoglobulinopathies; Immunopathology; Immunophenotyping; Male; Medical sciences; Molecular Sequence Data; multiple myeloma; Multiple Myeloma - immunology; Multiple Myeloma - pathology; Myeloma Proteins - metabolism; Plasma Cells - metabolism; polymerase chain reaction; Reverse Transcriptase Polymerase Chain Reaction; Sequence Analysis, DNA; Sequence Homology, Nucleic Acid; Human; Immunopathology; Clonality; IgA; IgE; Male; Malignant hemopathy; Plasmocyte; Myeloma; Case study; Immunoglobulinopathy; Lymphoproliferative syndrome; Elderly; Monoclonal immunoglobulin
• ISSN: 0902-4441; 1600-0609
• DOI: 10.1034/j.1600-0609.2000.065005348.x

: 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 Cα or Cε 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.