Abstract
Monoclonal gammopathies (MGs) are hematological diseases characterized by high levels of a monoclonal immunoglobulin (Ig) or M-protein. Within this group are patients with more than one M-protein, referred to as double MGs (DMGs). The M-proteins in DMG patients may have different heavy chain (HC) isotypes that are associated with different light chains (LCs), or different HCs that are LC matched. In this study, we examined the clonal relatedness of the M-proteins in the latter type in a cohort of 14 DMG patients. By using PCR, we identified 7/14 DMG patients that expressed two Ig HC isotypes with identical Ig HC variable (IGHV), diversity (IGHD), joining (IGHJ), and complementarity determining region (HCDR3) sequences. Two additional DMG patients had two Ig transcripts using the same IGHV, IGHD and IGHJ genes but with slight differences in variable region or HCDR3 mutations. LC analysis confirmed that a single LC was expressed in 3/7 DMG patients with identical HC transcripts and in the two DMGs with highly similar transcripts. The PCR findings were confirmed by immunofluorescence for HC and LC expression. Clonally related HC-dissimilar/LC-matched DMGs may occur often and defines a new subtype of MG that may serve as a tool for studies of disease pathogenesis.
Highlights
Monoclonal gammopathies (MGs) encompass a number of disorders characterized by the presence of a clonal expansion of malignant plasma cells (PCs) typically located within the bone marrow (BM)
When light chain (LC) expression was considered, 73% of those patients that expressed IgG/IgA expressed the same LC compared with 60% of IgG/IgM combinations.[14]. These results suggest that double MGs (DMGs) may include patients with independent malignant PC clones, as well as those that have clonally related malignant PCs resulting from class switch recombination (CSR) that has occurred at some point during disease pathogenesis
Review of clinical data for patient samples in our MG tissue bank identified 14 patients with DMGs characterized by two heavy chain (HC) and a single monoclonal LC upon immunofixation electrophoresis
Summary
Monoclonal gammopathies (MGs) encompass a number of disorders characterized by the presence of a clonal expansion of malignant plasma cells (PCs) typically located within the bone marrow (BM). These patients generally have high levels of monoclonal serum immunoglobulin (Ig) of a single isotype, which is referred to as the M-protein. MM, MGUS and AL have typically undergone IGH isotype switch to IgG, IgA or IgE, and studies in MM suggest that the malignant PCs no longer undergo SHM as evidenced by lack of intraclonal diversity.[7,8,9,10]
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