A VH4-34+ myeloma protein with weak autoreactivity

• Published in: Haematologica (Roma) Vol. 92; no. 5; pp. 690 - 693
• Main Authors: Froyland, Marianne, Thompson, Keith M, Thorpe, Susan J, Sahota, Surinder S, Gedde-Dahl, Tobias, Bogen, Bjarne
• Format: Journal Article
• Language: English
• Published: Pavia Haematologica 01.05.2007; Ferrata Storti Foundation
• Subjects: Aged; Amino Acid Sequence; Antibodies, Antinuclear - genetics; Antibodies, Antinuclear - immunology; Antibodies, Monoclonal - immunology; Antigen-Antibody Reactions; Autoimmunity; B-Lymphocytes - immunology; B-Lymphocytes - pathology; Base Sequence; Biological and medical sciences; Clone Cells - immunology; Clone Cells - pathology; DNA Mutational Analysis; Gene Rearrangement, B-Lymphocyte, Heavy Chain; Gene Rearrangement, B-Lymphocyte, Light Chain; Genes, Immunoglobulin; Hematologic and hematopoietic diseases; Humans; Immunodeficiencies. Immunoglobulinopathies; Immunoglobulin A - immunology; Immunoglobulin Heavy Chains - genetics; Immunoglobulin Variable Region - genetics; Immunoglobulinopathies; Immunopathology; Leukemias. Malignant lymphomas. Malignant reticulosis. Myelofibrosis; Mass Spectrometry; Medical sciences; Molecular Sequence Data; Multiple Myeloma - immunology; Multiple Myeloma - pathology; Myeloma Proteins - genetics; Myeloma Proteins - immunology; Neoplastic Stem Cells - immunology; Neoplastic Stem Cells - pathology; Polymerase Chain Reaction; Recombinant Fusion Proteins - immunology; Self Tolerance; Sequence Alignment; Sequence Deletion; Sequence Homology, Nucleic Acid; Human; Immunopathology; autoreactivity; VH4-34; Hematology; myeloma protein; B cell neoplasm; Malignant hemopathy; Lymphoid neoplasm; Gene expression; Myeloma; Immunoglobulinopathy; Lymphoproliferative syndrome; Genetics
• ISSN: 0390-6078; 1592-8721
• DOI: 10.3324/haematol.10850

From the Institute of Immunology, University of Oslo and Rikshospitalet-Radiumhospitalet Medical Center, Oslo, Norway (MF, KMT, BB); National Institute for Biological Standards and Control, Potters Bar, UK (SJT); Cancer Sciences Division, University of Southampton, Southampton, UK (SSS); Section of Hematology, Medical Department, Rikshospitalet-Radiumhospitalet Medical Center, Oslo, Norway (TGD) Correspondence: Keith M. Thompson, Institute of Immunology, Rikshospitalet, N-0027 Oslo, Norway. E-mail: keith.thompson{at}medisin.uio.no . It has been suggested that VH4-34 gene segment expression is counter-selected in multiple myeloma (MM) due to a self-tolerance mechanism. We cloned and sequenced a VH4-34 gene segment from bone marrow mononuclear cells of a stage III MM patient. We show that VH4-34 was expressed by the serum IgA myeloma (M)-protein, as demonstrated by reactivity with the VH4-34 specific 9G4 mAb and mass spectrometry (MS). The M-protein had weak reactivity with nuclei. These results demonstrate that VH4-34 may be expressed in secreted IgA M-protein with weak autoreactivity. Thus, counter-selection of VH4-34 is pronounced but not absolute in MM. Mechanisms of how VH4-34 can occasionally be expressed in MM and clinical implications are discussed. Key words: VH4-34, myeloma protein, autoreactivity.