Gerald Cohen1. 1. Division of Nephrology, Department of Medicine, University of Vienna, Vienna, Austria. cohen@nephro.imed3.akh-wien.ac.at
Abstract
BACKGROUND: Immunoglobulin light chains (IgLCs) are produced by B cells, slightly in excess of immunoglobulin heavy chains, and therefore are present in the serum of healthy adults in free form at low concentrations. Both the kappa and lambda form of these polyclonal IgLCs are mainly metabolized by the kidney and appear under normal conditions only in small amounts in the urine. In patients with a reduced or abolished kidney function, IgLC levels are increased. When overproduced in B cell lymphoproliferative disorders and deposited in the kidney, IgLCs can be, by themselves, a causative factor of renal diseases and the development of uremia. METHODS: We compared the effect of treatment with different low- and high-flux membranes on IgLC concentrations. The effect of free IgLCs on neutrophils, cells of the first-line unspecific immune defense, was assessed in in vitro experiments. RESULTS: We found that IgLC levels in hemodialysis and hemodiafiltration patients were higher than in pre-dialysis patients and that IgLC levels could not be brought into the normal range by currently available hemodialysis or hemodiafiltration treatments. IgLCs interfere with chemotaxis and the activation of glucose uptake, two essential neutrophil functions, and attenuate neutrophil apoptosis, the coordinated cell death that is crucial for the normal resolution of inflammation without tissue destruction. CONCLUSION: IgLCs occurring at increased levels in sera of patients with kidney failure modulate essential functions and the apoptotic cell death of neutrophils, and as a consequence contribute to the increased susceptibility to bacterial infections in uremic patients.
BACKGROUND: Immunoglobulin light chains (IgLCs) are produced by B cells, slightly in excess of immunoglobulin heavy chains, and therefore are present in the serum of healthy adults in free form at low concentrations. Both the kappa and lambda form of these polyclonal IgLCs are mainly metabolized by the kidney and appear under normal conditions only in small amounts in the urine. In patients with a reduced or abolished kidney function, IgLC levels are increased. When overproduced in B cell lymphoproliferative disorders and deposited in the kidney, IgLCs can be, by themselves, a causative factor of renal diseases and the development of uremia. METHODS: We compared the effect of treatment with different low- and high-flux membranes on IgLC concentrations. The effect of free IgLCs on neutrophils, cells of the first-line unspecific immune defense, was assessed in in vitro experiments. RESULTS: We found that IgLC levels in hemodialysis and hemodiafiltration patients were higher than in pre-dialysis patients and that IgLC levels could not be brought into the normal range by currently available hemodialysis or hemodiafiltration treatments. IgLCs interfere with chemotaxis and the activation of glucose uptake, two essential neutrophil functions, and attenuate neutrophil apoptosis, the coordinated cell death that is crucial for the normal resolution of inflammation without tissue destruction. CONCLUSION: IgLCs occurring at increased levels in sera of patients with kidney failure modulate essential functions and the apoptotic cell death of neutrophils, and as a consequence contribute to the increased susceptibility to bacterial infections in uremic patients.
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