The renal and hepatic distribution of Bence Jones proteins depends on glycosylation: a scintigraphic study in rats

Abstract

The aim of the present study was to evaluate renal and liver distribution of two monoclonal immunoglobulin light chains. The chains were purified individually from the urine of patients with multiple myeloma and characterized as lambda light chains with a molecular mass of 28 kDa. They were named BJg (high amount of galactose residues exposed) and BJs (sialic acid residues exposed) on the basis of carbohydrate content. A scintigraphic study was performed on male Wistar rats weighing 250 g for 60 min after iv administration of 1 mg of each protein (7.4 MBq), as the intact proteins and also after carbohydrate oxidation. Images were obtained with a Siemens gamma camera with a high-resolution collimator and processed with a MicroDelta system. Hepatic and renal distribution were established and are reported as percent of injected dose. Liver uptake of BJg was significantly higher than liver uptake of BJs (94.3 vs 81.4%) (P<0.05). This contributed to its greater removal from the intravascular compartment, and consequently lower kidney accumulation of BJg in comparison to BJs (5.7 vs 18.6%) (P<0.05). After carbohydrate oxidation, there was a decrease in hepatic accumulation of both proteins and consequently a higher renal overload. The tissue distribution of periodate-treated BJg was similar to that of native BJs: 82.7 vs 81.4% in the liver and 17.3 vs 18.6% in the kidneys. These observations indicate the important role of sugar residues of Bence Jones proteins for their recognition by specific membrane receptors, which leads to differential tissue accumulation and possible toxicity.

Calcium oxalate monohydrate aggregation induced by aggregation of desialylated Tamm-Horsfall protein

“…4) and relative abundance in urine, as well as the positive staining in Western blots from similar gels with specific antibodies. Band assignments are supported by earlier reports implicating serum proteins in urine, such as albumin, as promoters of THP aggregation [22], and by the observation that THP associates with other proteins (e.g., IgG light chains or Bence Jones protein) in renal cast formation [23, 39]. Based on the observation of the large number of associations between ds-THP and other urinary macromolecules, we anticipate that ds-THP aggregates formed during phase separation would trap many other proteins, which could foster stone formation by potentially altering the aggregate interactions with crystal surfaces or depleting the solution of molecularly dispersed proteins that serve as aggregation inhibitors.…”

“…Comparisons often are made between in vitro experiments at different pH, ionic strength, and THP concentrations, which significantly influence COM aggregation [20, 32]. THP aggregates have been reported in several in vitro studies [1, 9–11, 23, 25, 31, 32, 38, 39, 50, 52, 55, 65], yet THP aggregates have not been observed in freshly voided urine of healthy individuals [16]. Some have suggested that THP precipitation may be a first step in stone formation [16, 18, 46], but the role of THP aggregates in regulating COM aggregation is not well understood.…”

Germ Line Origin and Somatic Mutations Determine the Target Tissues in Systemic AL-Amyloidosis

“…It has been suggested from an experimental rat study that glycosylated immunoglobulin light chains preferably deposit in the liver [31]. This was not verified in the present study in which both glycosylated and nonglycosylated κ3a proteins formed heavy liver deposition.…”

Electrophoretic analysis of Bence Jones proteinuria

“…2-DE and other high resolution electrophoretic methods are also being used increasingly to detect and characterise the carbohydrate constituents of glycoproteins by the use of lectin probes following immunoblotting. This may be of particular interest in studies of nephrotoxicity as BJ proteins are glycosylated [91, 149±152] and differential glycosylation is of pathophysiological significance [153] in dictating tissue uptake of free LC [154] and fibrillogenesis [155].…”