Structure of the IgG3 γ heavy chain excreted in the urine of a patient with IgG-κ–type multiple myeloma

• Published in: Tenri Medical Bulletin Vol. 22; no. 2; pp. 64 - 70
• Main Authors: Matsumura, Mitsuko, Hayashida, Masahiko, Takata, Manami, Shimada, Masashi, Matsuo, Shuji
• Format: Journal Article
• Language: Japanese
• Published: Tenri Foundation, Tenri Institute of Medical Research 25.12.2019
• Subjects: Fc region; IgG3 subclass; immunofixation of urinary protein; multiple myeloma; Western blotting
• ISSN: 1344-1817; 2187-2244
• DOI: 10.12936/tenrikiyo.22-015

In patients with multiple myeloma (MM), when immunoglobulin (Ig) light chains are produced in excess of the corresponding heavy chains, the excess free light chains are freely filtered through the glomerular filtration barrier (i.e. 40–60 kDa) and excreted in the urine, referred to as Bence Jones protein (BJP). We report a patient with IgG-κ–type MM who excreted Ig γ heavy chain in the urine instead of BJP, which migrated at the fast-γ position on immunofixation. To determine the structure of the urinary Ig γ chain, we first performed Western blot (WB) analysis of the serum protein using anti-human Ig γ chain and found a 60-kDa protein band, which was larger than the 50-kDa IgG purified from normal human serum. We next subjected the urinary protein to a series of WB analyses under non-denaturing conditions against the Ig γ chain, Fc fragment, Fab fragment, and IgG subclasses, and found that the urinary protein contained 6–7 fragments of γ chain, ranging from 50 to 66 kDa, which reacted with anti-Fc and anti-IgG3 antibodies. This suggested that the IgG γ heavy chain in this MM patient belonged to the IgG3 subclass, characterized by the long hinge region and highest molecular weight among the IgG subclasses, and the urinary Ig γ chain was considered to represent dimers of the Fc fragments, which were generated by proteolytic cleavage at variable sites within the hinge region. As there are case reports of deposition of monoclonal IgG3 in the kidney, causing renal damage, our current approach may be applied to cases of MM in which a broad band at the fast-γ position that reacts with anti-IgG serum but lacks the associated light chain is detected on immunofixation of the urine in order to determine the subclass and structure of the excreted Ig γ chain.