Renal impairment is one of frequent and serious complications in patients with multiple myeloma (MM) and is associated with a higher incidence of infections and early death rate. The catalytic activity of Bence Jones proteins (BJP) affects the clinical processes of patients with MM, and can lead to renal impairment. Scientists point out that BJP have peptidolytic and nucleolytic activity, which can lead porcine kidney proximal tubule (LLC-PK1) to apoptosis in vitro experiments. By treating the cytotoxic BJP with serine protease inhibitor (DFP), BJP lost not only their catalytic activity, but also the cytotoxic effects. Therefore, further research on BJP will helpful to understand the pathogenesis of renal impairment in MM patients and may provide a new idea and measure for the treatment of MM with renal impairment. This article reviews the basic research and progress on the catalytic activity of BJP.
Animals ; Apoptosis ; Bence Jones Protein ; metabolism ; Humans ; Kidney ; pathology ; LLC-PK1 Cells ; Multiple Myeloma ; metabolism ; pathology ; Swine

This study was purposed to investigate the relationship between the catalysis of Bence Jones protein (BJP) in urine of patients with multiple myeloma(MM) and toxicity on the renal proximal tubular cells in vitro, and to explore the potential mechanism for the toxicity of BJP to renal impairment in patients with MM. The Michaelis-Menten constant (K(m)) and catalytic constant (k(cat)) of the amidase activity of BJP was calculated by Hanes equation. The LLC-PK1 cells were cultured with different concentration of BJP for 24 h, then proliferation of the cells were determined by MTT method and apoptosis were determined by flow cytometry. The results showed that the BJP from the MM patients with renal impairment significantly inhibited cell proliferation, as compared with that from MM patients without renal impairment. The BJP with higher k(cat) had higher toxicity to LLC-PK1 cells. BJP could induce apoptosis and necrosis of LLC-PK1 cells when reached a certain concentration and this effect enhanced with increase of BJP concentration. It is concluded that the catalysis of BJP and its toxicity to renal tubular epithelial cells has a positive correlation, and toxic effect of BJP on renal tubular epithelial cells results from inhibiting proliferation and inducing apoptosis and necrosis of the cells, which may be one of renal impairment mechanisms in MM patients.
Animals ; Bence Jones Protein ; metabolism ; toxicity ; Catalysis ; Coculture Techniques ; Epithelial Cells ; metabolism ; pathology ; Humans ; Kidney ; metabolism ; pathology ; Kidney Tubules ; cytology ; LLC-PK1 Cells ; Multiple Myeloma ; metabolism ; pathology ; Swine

A 58-yr-old man presented with leg edema and subacute weakness of his bilateral lower extremities. Urinary and serum immunoelectrophoresis revealed the presence of lambda-type Bence Jones proteins. He was ultimately diagnosed with monoclonal gammopathy of undetermined significance (MGUS). A renal biopsy specimen showed fibrillary glomerulonephritis (FGN), which was randomly arranged as 12-20 m nonbranching fibrils in the basement membranes. Immunofluorescence studies were negative for immunoglobulin (Ig)G, IgM, IgA, C3, and kappa light chains in the capillary walls and mesangial areas. A Congo red stain for amyloid was negative. Electromyography and nerve conduction velocity examinations results were compatible with the presence of demyelinating polyneuropathy. This case showed a rare combination of FGN, without Ig deposition, and MGUS combined with chronic inflammatory demyelinating polyneuropathy (CIDP).
Amyloid ; Basement Membrane ; Bence Jones Protein ; Biopsy ; Capillaries ; Congo Red ; Edema ; Electromyography ; Fluorescent Antibody Technique ; Glomerulonephritis* ; Immunoelectrophoresis ; Immunoglobulin A ; Immunoglobulin M ; Immunoglobulins ; Leg ; Lower Extremity ; Monoclonal Gammopathy of Undetermined Significance ; Neural Conduction ; Paraproteinemias ; Polyneuropathies*