title: Spontaneous monoclonal immunoglobulin-secreting peripheral blood mononuclear cells as a marker of disease severity in multiple myeloma.
abstract: Peripheral blood from patients with multiple myeloma (MM) contains a small number of plasma cells related to the bone marrow tumour cells by their cytoplasmic immunoglobulin (Ig), their cell membrane antigen expression and/or their gene rearrangements, but hitherto the monoclonal Ig (M-Ig) production by circulating cells has not been reported. Using a two-colour ELISPOT assay, Ig-secreting cells (Ig-SCs) were detected in the blood of 28 MM and five Waldenstrom's macroglobulinaemia (WM) patients. The number of cells that spontaneously produced an Ig isotype similar to that of the M-Ig in serum was greater than that of the other Ig-SCs. MM patients presented an excess of circulating heavy-chain (alpha or gamma) Ig-SCs (0.38% of the PBMC) with kappa or lambda light chains (0.48%) compared with the number of cells secreting the other heavy- (0.02%) and light-chain isotypes (0.03%). WM patients also presented high numbers of cells secreting the mu-heavy-chain isotype (0.66%). The Ig synthesized in vitro was characterized as monoclonal, and the M-Ig secretory capacity of the peripheral blood cells was similar to that observed for Ig-SCs from polyclonal activated B cells in vivo. The number of these monoclonal cells was significantly increased in patients in an advanced stage of MM (I/II vs. III, P < 0.001) and correlated with the serum beta-2 microglobulin concentration (r = 0. 69; P < 0.0003). The number of M-Ig-SCs in MM patients could be a useful marker for evaluating the progression of multiple myeloma.
authors.affiliation: Centre de Recherches de Biochimie Macromoléculaire, Laboratoire des Infections Rétrovirales et Signalisation Cellulaire, Institut de Biologie, 2 Bd Henri IV, Montpellier, France.
authors.forename: F
authors.initials: F
authors.lastname: Cordoba
authors.forename: T
authors.initials: T
authors.lastname: Lavabre-Bertrand
authors.forename: S L
authors.initials: SL
authors.lastname: Salhi
authors.forename: M F
authors.initials: MF
authors.lastname: Huguet
authors.forename: J
authors.initials: J
authors.lastname: Gerfaux
authors.forename: J F
authors.initials: JF
authors.lastname: Rossi
authors.forename: J P
authors.initials: JP
authors.lastname: Vendrell
mesh_terms: D000328:Adult; D000368:Aged; D000921:Antibody-Producing Cells / Q000276:immunology*; D015415:Biomarkers / Q000097:blood; D018450:Disease Progression; D004797:Enzyme-Linked Immunosorbent Assay / Q000379:methods; D005260:Female; D006801:Humans; D007132:Immunoglobulin Isotypes / Q000276:immunology; D007963:Leukocytes, Mononuclear / Q000276:immunology; D008297:Male; D008875:Middle Aged; D009101:Multiple Myeloma / Q000276:immunology*; D010950:Plasma Cells / Q000276:immunology; D008258:Waldenstrom Macroglobulinemia / Q000276:immunology; D001613:beta 2-Microglobulin / Q000032:analysis
chemical_list: D015415:Biomarkers; D007132:Immunoglobulin Isotypes; D001613:beta 2-Microglobulin