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Amyloid Versus Non-Amyloid Immunoglobulin Deposits
Published in Gilles Grateau, Robert A. Kyle, Martha Skinner, Amyloid and Amyloidosis, 2004
LCDD is usually diagnosed by renal biopsy which shows: a) by immunofluorescence, linear LC deposits within glomerular and tubular basement membranes (97% of cases); b) by electron microscopy, the prototypic granular electron-dense deposits (77% of cases); and c) by light microscopy, nodular sclerosing glomerulopathy (51% of cases) (6). Myeloma cast nephropathy can be associated in 16%–32% of the cases and AL amyloidosis in 3%–33% of patients. Monoclonal protein is detected by immunofixation in serum or urine in 94% of LCDD patients with a κ/λ ratio of 68/32. The deposits may be formed by heavy chain (HC) instead of LC constituting the so-called heavy chain deposition disease (HCDD). Although these HC have a deletion of the CH1 domain, this deletion seems necessary but not sufficient for deposition, since VH probably also contributes to tissue deposition. In ∼10% of LCDD monotypic HC is associated with monotypic LC in deposits (light and heavy chain deposition disease, LHCDD).
Structural Bases of Light Chain-Related Pathology
Published in Maurizio Zanetti, J. Donald Capra, The Antibodies, 1999
Fred J. Stevens, Deborah T. Weiss, Alan Solomon
Monoclonal light chains, i.e., Bence Jones proteins, are responsible for the characteristic pathologic features found in patients with the light chain-related diseases that include myeloma (cast) nephropathy (MCN), light chain deposition disease (LCDD), light chain amyloidosis (AL), and acquired Fanconi’s syndrome (AFS). These disorders result from clonal proliferation of plasma cells that leads to the deposition of their Ig products as amorphous casts, punctate precipitates, highly ordered fibrils, or intracellular crystals, respectively (Figure 1). Such deposits in the kidney, heart, liver, and other vital structures result in impairment of organ function and ultimately account for the morbidity and eventual death of patients with these illnesses (Gallo et al, 1989; Buxbaum et al., 1990; Ofila et al, 1991; Stevens et al, 1991; Aucouturier et al., 1993; Solomon and Weiss, 1993; Bellotti and Merlini, 1996; Bellotti et al, 1996; Schiffer, 1996; Dhodapkar et al, 1997). Remarkably, not all Bence Jones proteins are harmful. In some cases, despite the daily excretion of prodigious amounts of protein (>50 g), there is no demonstrable pathology. Further, there is no apparent correlation between the amount of Bence Jones protein excreted and the type or extent of tissue deposition.
Management of multiple myeloma bone disease: impact of treatment on renal function
Published in Expert Review of Hematology, 2018
Nikolaos Kanellias, Maria Gavriatopoulou, Evangelos Terpos, Meletios Athanasios Dimopoulos
Renal impairment and bone disease are two of the main manifestations of multiple myeloma (MM). Renal impairment remains a common and severe myeloma complication which is associated with significant morbidity and increased early mortality [1,2]. The incidence of renal impairment in newly diagnosed cases of MM is 20–40% based on the definition used [3–6]. Renal impairment manifestations have a broad spectrum, which ranges from mild kidney injury, that may be quickly reversible (e.g. volume depletion) to severe acute kidney injury requiring renal replacement therapy. A significant proportion of patients with relapsed refractory MM (20%–25%) can also develop renal impairment during the course of the disease [7]. The most common form of renal damage is myeloma cast nephropathy (myeloma kidney). This is the most frequent pathophysiologic form of renal damage, in which the amount of free light chains that have not been absorbed in the proximal tubule, form casts by binding to a specific site of Tamm-Horsfall protein in the distal nephron [1,8,9]. The casts formed, lead to obstruction of the distal tubule and the ascending loop of Henle [10–12]. Apart from cast formation, light chains induce the production of pro-inflammatory cytokines which promote the production and deposition of matrix protein leading to fibrosis of the nephron [13–15].
Phenotypic plasticity of mesenchymal stem cells is crucial for mesangial repair in a model of immunoglobulin light chain-associated mesangial damage
Published in Ultrastructural Pathology, 2018
Guillermo A. Herrera, Jiamin Teng, Chun Zeng, Hongzhi Xu, Man Liang, J Steven Alexander, Bing Liu, Chris Boyer, Elba A. Turbat-Herrera
Free LCs were purified from the urine of patients with renal biopsy-proven (AL-amyloidosis) AL-Am (n = 4), LCDD (n = 4) and myeloma cast nephropathy (MCN) (n = 4) control LCs following a well described protocol extensively utilized.29 Ammonium sulfate was added to the urine to achieve 70% saturation. The precipitate was re-dissolved in distilled water and dialyzed at least 24 h using cellulose dialysis tubing (Spectra/Por Membrane Tubing, Thermo Fisher Scientific, Waltham, Massachusetts) with a 12,000–14,000 Da cutoff, against distilled water and then in a 0.01 M sodium phosphate buffer, pH 7.6. The urine was subsequently spun in a tip ending centrifuge bottle to get rid of debris. The supernatant was filtered through 0.2 μm membranes and further centrifuged with 300 KD MWCO membranes (Pall Life Sciences, Port Washington, NY). The material recovered was centrifuged again and the part obtained in the <300 KD portion was concentrated using a 3 KD MWCO membrane and then dialyzed using a 3500 MWCO membrane tube.
Ultrastructural identification of a proximal tubulopathy without crystals in a relapsed multiple myeloma patient
Published in Ultrastructural Pathology, 2018
John K Brealey, Yung Tran, Ruth Ninnes, Asanga Abeyaratne
Light microscopy – a single core of mostly cortical tissue containing 74 glomeruli (aggregated from the H&E sections and special stains) revealed capsular fibrosis in 9% of the glomeruli, 8% glomerular obsolescence and 15% interstitial fibrosis. No convincing evidence of myeloma-related renal disease was evident. Some tubules contained granular proteinaceous casts or red cell casts; however, refractile casts with a cellular reaction, as seen in myeloma cast nephropathy, were not identified. The Congo red stain for amyloid was negative.