Proteins in plasma and urine
Martin Andrew Crook in Clinical Biochemistry & Metabolic Medicine, 2013
The immunoglobulin most frequently increased is IgG, and, less commonly, IgA (about 2.5:1). Occasionally, IgM, IgD or IgE is found, the last two being very rare. Bence Jones protein may sometimes be present in plasma if renal failure is present. In about 20 per cent of cases, no paraprotein is detected in the plasma but BJP is detected in urine. Rarely, neither a paraprotein nor BJP can be found. In either case there is usually immune paresis. In IgD myelomatosis an increase in λ-globulin concentration may not be detectable by routine electrophoresis. The paraprotein should be typed and the plasma concentration monitored to follow progress. The serum free light chain ratio (κ to γ) may also be abnormal. This ratio is normally about 0.26–1.65 and can be useful in monitoring patients with low levels of paraprotein (monoclonal or ‘M’ protein) and of early treatment response and disease relapse.
Structural Bases of Light Chain-Related Pathology
Maurizio Zanetti, J. Donald Capra in The Antibodies, 1999
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.
Case 28: Bilateral Hip Pain
Layne Kerry, Janice Rymer in 100 Diagnostic Dilemmas in Clinical Medicine, 2017
A chest x-ray showed a right apical cavitating lesion that was unchanged compared with previous films. Pelvic and hip x-rays showed degenerative changes at both hip joints with narrowing of the joint space and marginal osteophytosis, consistent with osteoarthritis. A lateral spine x-ray revealed an anterior wedge fracture at the level of T4/T5 and loss of vertebral height at T12 through to L3. A myeloma screen was performed – the immunoglobulin levels were within normal range and there were no Bence Jones protein in the urine.
Biochemical and biophysical properties of an unreported T96R mutation causing transthyretin cardiac amyloidosis
Published in Amyloid, 2023
Meng Jiang, Mengdie Wang, Zhengyu Tao, Yezi Chai, Qiming Liu, Qifan Lu, Qizhen Wu, Xiaoying Ying, Yanan Huang, Ying Nie, Yuqi Tang, Xin Zhang, Yu Liu, Jun Pu
Endomyocardial biopsy and subsequent Congo red staining confirmed amyloidosis deposition. Cardiomyocyte atrophy along with disordered, degenerated and necrotic myofibrils were observed using electron microscopy. The muscle cell space was widened. A large number of amyloid fibers were seen between muscle cells and vessel walls and had a disordered arrangement (Figure 1(C)). To rule out light-chain amyloidosis, additional laboratory studies were conducted. No positive findings were shown when assessing Bence Jones protein, free light chain and immune electrophoresis. Tc-99m-PYP testing for ATTR amyloidosis was not confirmative (Figure 1(C)). Although the H/CL ratio was 1.7, the pattern of uptake indicated a more focal, intense uptake rather than a diffuse one. Subsequent genetic testing showed that the patient was heterozygous for the T96R pathogenic variant c.347C > G (ATTR p.T116R), consistent with a diagnosis of hereditary ATTR (Figure 1(D)).
Sequential renal biopsy in a patient with lupus nephritis and fingerprint deposits: a case report
Published in Modern Rheumatology Case Reports, 2018
Naoya Toriu, Rikako Hiramatsu, Hiroki Mizuno, Daisuke Ikuma, Akinari Sekine, Noriko Hayami, Keiichi Sumida, Masayuki Yamanouchi, Eiko Hasegawa, Junichi Hoshino, Naoki Sawa, Kenmei Takaichi, Kenichi Ohashi, Takeshi Fujii, Motoko Yanagita, Yoshifumi Ubara
In 1993, a 37-year-old Japanese man was admitted to our hospital with fever and bilateral arthritis of the hands, legs, and shoulders. On admission, the patient was 171.3 cm tall and weighed 54 kg, with a blood pressure of 110/60 mmHg, heart rate of 80/min, and temperature of 38.0 °C. He had no past history and familial history. Laboratory findings showed pancytopenia (white blood cell count of 2700/μL with 54 lymphocytes/μL, red blood cell count of 3.12 × 104/μL, Hb of 9.3 g/dL, and platelet count of 3.12 × 106/μl), positivity for anti-nuclear antibody (of homogenous type and speckled type) and anti-DNA antibody (144.9 U/mL), hypocomplementaemia (serum C3 of 20.1 mg/dL, C4 of 14 mg/dL, and CH50 of 9 U/mL), and proteinuria (24-h urinary protein excretion of 1.65 g). Anti-Sm antibody was nagatibe, and anti-SS-A and SS-B antibody were positive. Cryoglobulins were weakly positive and were classified as type 2 (Table 1). An electrocardiogram did not show low voltage in limb hand and echocardiography did not show cardiac hypertrophy. Serum monoclonal protein and urinary Bence Jones protein were negative. Systemic lupus erythematous was diagnosed and renal biopsy was performed.
The role of cystatin C as a proteasome inhibitor in multiple myeloma
Published in Hematology, 2020
Yijing Jiang, Jie Zhang, Chenlu Zhang, Lemin Hong, Yuwen Jiang, Ling Lu, Hongming Huang, Dan Guo
Multiple myeloma (MM) is a widespread hematological tumor characterized by the aberrant accumulation of bone marrow plasma cells (PCs) in the bone marrow. Abnormal plasma cell proliferation in the bone marrow leads to a large number of abnormal monoclonal immunoglobulins in the serum, followed by Bence-Jones protein, anemia, and abnormal immune function cause renal function damage. Myeloma nephropathy is relatively common complications in patients with MM. Generally, the majority of severe renal injuries in patients with multiple myeloma are associated with immunoglobulin (Ig) free light chains (FLCs) [9,10]. Substantial FLCs (nephrotoxic proteins) accumulated in the proximal tubular epithelium are responsible for most tubulointerstitial injuries. Monoclonal light chains in renal tubules stimulate the production of some proinflammatory cytokines, including macrophage chemoattractant protein-1 (MCP-1), interleukin-6 (IL-6), and tumor necrosis factor α (TNF-α), which subsequently, rapidly leads to renal tubulointerstitial fibrosis [11,12]. Light chain proteins can also cause glomerular function impairment when deposited on the glomerular basement membrane (GBM) and mesangial area [13]. Therefore, it remains critical that the extent of kidney damage at the early stages of multiple myeloma diagnosis be identified and early intervention provided.
Related Knowledge Centers
- Anemia
- Globulin
- Immunoglobulin Light Chain
- Kidney Failure
- Protein
- Urine
- Bone Marrow
- Waldenstrom Macroglobulinemia
- Plasma Cell
- Multiple Myeloma
- Waldenström Macroglobulinemia