IgG1-kappa biclonal gammopathy associated with multiple myeloma suggests a regulatory mechanism.
Multiclonal gammopathies associated with multiple myeloma may result either from a neoplastic transformation of a cell clone undergoing immunoglobulin class switching or from independent transforming events yielding proliferation of unrelated plasma cell clones. The simultaneous presence of more than one neoplastic clone may possess regulatory implications in terms of cell proliferation, clonal expansion, secretion of M-components or response to chemotherapy. We report a patient, diagnosed with multiple myeloma stage IIIa, who presented with two well-defined homogeneous IgG1-kappa components in the serum (designated WER-1 and WER-2) with striking differences in their plasma concentration and response to the classic melphalan/prednisone treatment. Immunochemical characterization and amino terminal sequence analysis of both the heavy and light chains of each M-component undoubtedly determined their biclonal origin. WER-1 was identified as IgG1(VHII)-kappaI while WER-2 was classified as IgG1(VHIII)-kappaIII. The plateau phase was characterized by very low or undetectable levels of WER-2, a high, almost constant, concentration of WER-1 and the absence of Bence Jones proteinuria, whereas these parameters were completely reversed during the escape phase with levels resembling those observed at the time of diagnosis. The statistically significant negative correlation between the biclonal components and the different susceptibility to the treatment clearly suggests regulatory interactions between the clones WER-1 and WER-2.
Pizzolato
M
M
Department of Clinical Biochemistry, University of Buenos Aires, Argentina.
Bragantini
G
G
Bresciani
P
P
Pavlovsky
S
S
Chuba
J
J
Vidal
R
R
Rostagno
A
A
Ghiso
J
J
D000368:Aged; D018906:Antineoplastic Agents, Alkylating / Q000008:administration & dosage; D018931:Antineoplastic Agents, Hormonal / Q000008:administration & dosage; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D001536:Bence Jones Protein / Q000652:urine; D017809:Fatal Outcome; D006801:Humans; D007070:Immunoglobulin A / Q000032:analysis; D007074:Immunoglobulin G / Q000032:analysis*; D007075:Immunoglobulin M / Q000032:analysis; D016898:Interferon-alpha / Q000008:administration & dosage; D008297:Male; D008558:Melphalan / Q000008:administration & dosage; D009101:Multiple Myeloma / Q000150:complications* / Q000276:immunology / Q000628:therapy; D010265:Paraproteinemias / Q000150:complications* / Q000276:immunology / Q000628:therapy; D010266:Paraproteins / Q000032:analysis*; D011241:Prednisone / Q000008:administration & dosage; D017421:Sequence Analysis
D018906:Antineoplastic Agents, Alkylating; D018931:Antineoplastic Agents, Hormonal; D007070:Immunoglobulin A; D007074:Immunoglobulin G; D007075:Immunoglobulin M; D016898:Interferon-alpha; D010266:Paraproteins; D001536:Bence Jones Protein; D008558:Melphalan; D011241:Prednisone