Immunoglobulin class switch from IgA1 to IgG2 and simultaneous association with Bence Jones proteinuria in the escape phase in a myeloma patient treated with interferon alpha.
Immunoglobulin (Ig) class switch from alpha1 to gamma2 associated with kappa-type Bence Jones proteinuria was evident in the escape phase of an IgA1 myeloma patient treated with interferon alpha (IFN alpha). The additional M-protein, IgG2-kappa, level rapidly increased and was associated with Bence Jones proteinuria, whereas monoclonal IgA1-kappa progressively declined. The N-terminal 21 amino acid sequences of the kappa-chains of monoclonal IgA1, IgG2 and the Bence Jones protein were the same. The N-terminal 15 amino acid sequence of the gamma2-chain was identical to that of the alpha1-chain. Based on these findings, the IgA1 myeloma cells underwent a class switch in CH gene expression from alpha1 to gamma2 with cell differentiation in vivo. The mechanism of the Ig class switching is discussed from three points of view: (1) Increase in immature and plasmablastic myeloma cells in the escape phase is susceptible to Ig class switching by the T-cell-derived cytokines. (2) We presumed that administered IFN alpha increased the amounts of secreted IFN gamma from the Th1 cells. (3) Due to a large quantity of IFN gamma, an inducer of Cgamma2 germline transcript, Ig class switching occurred stepwise from the alpha1 constant region gene to the next 3'CH gamma2 gene.
Kozuru
M
M
Department of Haematology, National Kyushu Cancer Centre, Minami-ku, Fukuoka, Japan.
Uike
N
N
Takahira
H
H
Yufu
Y
Y
Goto
T
T
Muta
K
K
D000368:Aged; D001536:Bence Jones Protein / Q000652:urine*; D005260:Female; D006801:Humans; D007070:Immunoglobulin A / Q000276:immunology*; D007074:Immunoglobulin G / Q000276:immunology*; D007147:Immunoglobulin Light Chains / Q000032:analysis; D016130:Immunophenotyping; D016898:Interferon-alpha / Q000627:therapeutic use*; D009101:Multiple Myeloma / Q000276:immunology / Q000628:therapy*; D010950:Plasma Cells / Q000276:immunology
D007070:Immunoglobulin A; D007074:Immunoglobulin G; D007147:Immunoglobulin Light Chains; D016898:Interferon-alpha; D001536:Bence Jones Protein