Urinary Light Chains Research Articles

Interferon therapy in multiple myeloma: Failure of human fibroblast interferon administration to affect the course of light chain disease

Fibroblast interferon at a dosage of 28 × 10 6 U/wk failed to influence disease progression in a preterminal case of therapy-resistant light chain myeloma. In a second case, that had not previously been treated, a first course of fibroblast interferon ( 30 × 10 6 U/wk ) associated with corticosteroids remained without effect. In this patient subsequent leukocyte interferon treatment was associated with a decrease in urinary light chain excretion and normalization of calcaemia, all other parameters remaining unaltered. A third patient with light chain disease was resistant to chemotherapy ab origine. None of the disease parameters responded to either fibroblast or leukocyte interferon therapy ( 21 × 10 6 U/wk ). During therapy a downward trend occurred in the relative number of lymphocytes characterizable as B and T cells. Mitogenic reactivity remained unchanged except for a downward trend, during fibroblast interferon therapy, in reactivity to PHA and Con A after 6 days culturing. Spontaneous (background) mitogenesis upon culture showed an upward trend.

Urinary excretion of albumin, beta-2-microglobulin and light chains in pre-eclampsia, essential hypertension in pregnancy and normotensive pregnant and non-pregnant control subjects

Urinary albumin, beta-2-microglobulin (β2m) and light chain excretions were determined in first, second and third trimester of pregnancy and 5 days, 3 months and 6 months after delivery in patients with pre-eclampsia, essential hypertension and transient hypertension in pregnancy, and in normotensive pregnant and non-pregnant control subjects. In pre-eclampsia, albumin excretion was markedly reduced after delivery and did not deviate significantly from either the normotensive non-pregnant control group or the normotensive pregnant control group 6 months after delivery; light chain exeretion in pregnancy and 5 days after parturition was higher than in both normotensive non-pregnant and pregnant control subjects. In essential hypertension, albumin excretion was higher 5 days after delivery than in non-pregnant control subjects and reduced on examination 3 and 6 months later, but still significantly higher than in the normotensive control groups. In transient hypertension and normotensive pregnant subjects, ...

Monoclonal immunoglobulin light chains in urine of patients with lymphoma.

Fourteen of 31 patients with non-Hodgkin's lymphoma or chronic lymphocytic leukaemia had a monoclonal immunoglobulin light chain detectable in their urine. These chains are believed to be synthesized by the B lymphoid cells comprising the tumour. Upon comparing the different cases, the occurrence and amount of monoclonal light chain showed no dependence upon the extent of tumour, the presence of leukaemic component, or exposure to cytotoxic therapy. The method of detection involved purifying the urinary light chains by immunosorption, and examining their electrophoretic distributions so as to distinguish between the homogeneous monoclonal chains and their heterogeneous normal analogues.

A case of the Light Chain Disease Associated with the Combined Light Chain Nephropathy

A 34 year old male was admitted to the hospital with polydipsia, polyuria, severe bone pain and deformity of thorax. Twelve years previously, glycosuria and proteinuria had been established.He had a severe Bence-Jones proteinuria. The presence of κ-type light chain in serum and urine was demonstrated by tne immunoelectrophoreses. Residual immunoglobulins were markidly decreased. However, the percentage of plasma cells in the bone marrow was less than 10% and few atypical plasma cells were found. Therefore, it seems likely that he has not yet developed multiple myeloma but has been in the premyelomatic state.He had also the Fanconi's syndrome, the distal renal tubular acidosis and the renal diabetes inspidus.Therefore, the diagnosis of the light chain (κ) disease associated with the combined light chain nephropathy was made. Until recently only 8 cases of the combined light chain nephropathy (Smithline, 1976) have been reported in literatures.

全身性エリテマトーデスにおける尿中の低分子蛋白

By the use of radioimmunoassay, urinary β2-microglobulin concentration was mesured in 49 patients with systemic lupus erythematosus (SLE). The urinary β2-microglobulin was significantly elevated in SLE (p<0.01). The level of urinary β2-microglobulin did not correlate with the level of serum complement, antibody to DNA or the massive proteinuria. It was associated with urinary free light chain and the degree of renal tubular damage, but not with the glomerular lesions observed in renal biopsy specimens. The elevated level of β2-microglobulin in urine was most likely due to increased excretion of β2-microglobulin from involved tubulus or direct secretion from lymphocytes infiltrating the interstitium. The measurement of the level of urinary β2-microglobulin is useful for estimating the extent of renal interstitial damage in patients with SLE.

Light chain polymerism in normal individuals in patients with severe proteinuria and in normals with inhibited tubular protein reabsorption by lysine.

The polymeric forms of free kappa and lambda light chains were estimated in serum and urine from twelve normal individuals, from seven patients with nephrotic syndrome associated with normal GFR, and from eleven normal persons after inhibition of renal tubular protein reabsorption by lysine. The investigation showed that the serum concentrations of the monomeric and dimeric forms of light chains were similar in the three groups. The urinary excretion was increased in patients with nephrotic syndrome, the mean excretion of kappa chains being 9.2 mg/24 h and of lambda 6.6 mg/24 h compared with normal excretion of 2.2 mg/24 h for kappa and 1.0 mg/24 h for lambda. After inhibition of tubular protein reabsorption, the urinary light chains excretion increased to 101.3 mg/24 h for kappa and 40.0 mg/24 h for lambda chains, i.e. approximately 40 times normal level. The relative concentrations in the urine of the monomeric and dimeric forms of the two chain types were varied widely in the three groups investigated, particularly for lambda monomers where a low excretion rate and clearance value was found during inhibition of the protein reabsorption. The reason for the variations were found to be differences in polymerization and consequently differences in glomerular filtration. Evidence for a preferential reabsorption of any of the chain types or polymers was not seen.

Presence of free light chains in urine of patients suffering from subacute sclerosing panencephalitis.

The immunoelectrophoretic analysis of CSF of patients suffering from subacute sclerosing panencephalitis (SSPE) showed modifications in the IgG pattern. Using the same method and also the double diffusion in agar technique we have revealed in these patients the presence of free light chains in most urines studied. Isofocusing analysis of free light chains from urines of two patients suggests that these chains could be a monoclonal product.

Response to therapy in IgG myeloma patients excreting lambda or kappa light chains: CALGB experience

Sixty-eight previously untreated patients with IgG myeloma who were entered into five protocols of Cancer and Leukemia Group B (CALGB) were studied in order to determine the possible influence of excretion of kappa versus lambda urinary light chains on responses to treatment and survival. All patients in these protocols were included if the serum and urine protein abnormalities were confirmed by one of the two group reference laboratories. Pretreatment characteristics of the two groups of patients did not differ significantly. Of 44 patients with kappa Bence Jones proteinuria, 19 patients (43%) had good responses to treatment, whereas only 3 of 24 patients (13%) with lambda Bence Jones proteinuria had good responses (p = 0.02). Survival for the patients excreting kappa light chains was significantly better than survival for patients excreting lambda chains (median survival 31 versus 12 mo, p = 0.02).

Gn=“left”>Response to Therapy in IgG Myeloma Patients Excreting Lambda or Kappa Light Chains: CALGB Experience

AbstractSixty-eight previously untreated patients with IgG myeloma who were entered into five protocols of Cancer and Leukemia Group B (CALGB) were studied in order to determine the possible influence of excretion of kappa versus lambda urinary light chains on responses to treatment and survival. All patients in these protocols were included if the serum and urine protein abnormalities were confirmed by one of the two group reference laboratories. Pretreatment characteristics of the two groups of patients did not differ significantly. Of 44 patients with kappa Bence Jones proteinuria, 19 patients (43%) had good responses to treatment, whereas only 3 of 24 patients (13%) with lambda Bence Jones proteinuria had good responses (p = 0.02). Survival for the patients excreting kappa light chains was significantly better than survival for patients excreting lambda chains (median survival 31 versus 12 mo. p = 0.02).

Staging of myeloma. A preliminary study of staging factors and treatment in different stages.

Attempts were made to find prognostic factors in myeloma. In 16 deceased patients, urinary light chains, skeletal lesions, and the quantity of the monoclonal protein fraction in the serum were correlated to prognosis, in contrast to the electrophoretic mobility of the monoclonal fraction, the hemoglobin, the serum creatinine value, the serum calcium, or the intestinal calcium absorption. Skeletal calcium uptake was only numerically higher in mild myeloma than in advanced myeloma. Since these findings partially agreed with the staging procedure previously proposed by Salmon, a modification of this procedure was used to stage 50 myeloma patients. Survival was statistically significantly shorter in stage III than in stage I. A differentiated treatement with melphalan-prednisone in stage I, cytoxan infusions in stage II, and vincristine-cytoxan-prednisone in stage III is proposed. A preliminary comparison of nine patients in stage II-III given intensive treatment with 23 given melphalan-prednisone suggests a numerically, but not as yet a statistically significant increase in survival in the intensively treated group, which seems to have an 80% 2-year survival.

Plasma cell dyscrasias (except myeloma)

T HE PLASMA CELL DYSCRASIAS are a group of related diseases that are characterized by proliferation of immunoglobulin-producing cells, usually from a single clone or strain. These cells secrete immunoglobulins or their components as a homogenous protein detectable by serum protein electrophoresis as a single spike (designated M-protein for monoclonal), or by urine protein electrophoresis as a peak (urinary light chains). Synonyms for these disorders are monoclonal gammopathy, dysgammaglobulinemia, and paraimmunoglobulinopathy. In this paper, we will review the clinical and laboratory aspects and bone radiology of three disorders of this group, macroglobulinemia, amyloidosis, and heavy chain disease.

A urinary cryo-Bence Jones protein gelling at room temperature

The clinical details and immunochemical investigation of a patient with Bence Jones myeloma who was excreting large amounts of a urinary light chain cryoglobulin are described. The cryoprotein was of especial interest as it was in the gel phase not only at 4° but also at room temperature.

Primary acquired sideroblastic anemia preceding monoclonal gammopathy and malignant lymphoma

An elderly white man presented as a typical example of primary acquired Sideroblastic anemia in 1965. Three years later, the peripheral blood smear revealed the presence of atypical and immature lymphocytes. Two small palpable lymph nodes were noted in the right axilla and a possibly enlarged spleen on intravenous pyelogram in 1969; however, a biopsy specimen of the lymph node failed to show any evidence for malignant lymphoma. In 1970, a monoclonal gammopathy, immunoglobulin G (IgG), subclass G 1, kappa, Gm (afb) and InV (1-) was documented. At that time, the presence of kappa light chain in urine was also noted. The patient died of bronchopneumonia in February 1971. Autopsy revealed malignant lymphoma, poorly differentiated type, involving the abdominal lymph nodes and spleen. This unusual development of malignant lymphoma in a patient with primary acquired sideroblastic anemia has not, to the best of our knowledge, been recorded previously. Whether or not primary acquired sideroblastic anemia represents a prelymphoplasmaproliferative or other premalignant blood disorder can be settled only by longitudinal studies in a large number of such patients.

Fanconi syndrome with renal tubular acidosis and light chain proteinuria.

A patient is described with Sjogren’s syndrome, the Fanconi syndrome, proximal and distal renal tubular acidosis, and elevations of both blood and urine gamma globulin and light chains. Triamterene ha

Urinary immunoglobulins in patients with cancer.

Urinary immunoglobulins were studied in 63 patients with different types of cancer. The main object was to investigate the occurrence of monoclonal immunoglobulins, primarily of the Bence Jones type, in the urine. Cancer of the breast dominated in the group as a whole (23 cases), and different forms of gastrointestinal cancer dominated among the remaining cases. Elevated levels of urinary light chains were discovered in 8 out of 63 patients. A marked predominance of kappa‐type light chains was noted, similar to what has been observed in leukaemia and lymphoma. However, they lacked the electrophoretic homogeneity of Bence Jones protein.

Ultrastructural study of human myeloma cells in relation to its function.

The ultrastructure of neoplastic plasma cells from a patient with prolonged multiple myeloma was studied in relation to its function, that is, the secretion of immunoglobulin light chain. Peroxidase-labelled antibodies, each monospecific to its immunoglobulin component chain, were used to localize intracellular immunoglobulin within myeloma cells under the electron microscope. By this method, only the kappa type light chain was detected within myeloma cells in bone marrow tissue of this patient, indicating that the occurrence of free kappa type light chains in serum and urine was due to the cessation of heavy chain synthesis within the myeloma cells. The kappa chain was demonstrated as conspicuous electron-dense precipitates in ergastoplasm, its cisternal space, external layer of nuclear membrane, and ribosomes associated with ergastoplasm and nuclear membrane. No immunoglobulin was demonstrated in an atypical Golgi complex, an organelle which is ordinarily engaged in protein synthesis. Numerous crystalline structures and similar inclusion bodies found in myeloma cells appeared to have arisen from the Golgi area, but they did not ever react with the peroxidase label. Discharge of the kappa chain from the cell seems to be carried out through cell fragmentation, possibly caused by progressive distension of the ergastoplasmic cavity.

Application of a modified technique to study urinary immunoglobulin light chain and whole IgG excretion in normal human subjects and patients with immune-related disorders.

Abstract While urinary L-chain and IgG excretion has been well studied in normal human subjects, it has received little attention in disease, in large part because of lack of a feasible technique for studying large numbers of patients. The present report describes a simplified technique performed on 350 ml. of urine and involving ultrafiltration, radial immunodiffusion, batching with DEAE Sephadex, and acid 8M urea starch gel electrophoresis. Application of the technique to 10 normal and 69 abnormal subjects free of gross clinical proteinuria revealed elevated L-chain excretion in none of 5 patients with chronic lymphatic leukemia (CLL), 4 of 7 with lymphosarcoma (LSC), 5 of 5 with acute infectious mononucleosis, 2 of 5 with metastatic adenocarcinoma, none of 8 with idiopathic acquired autoimmune hemolytic anemia, 1 of 3 with idiopathic thrombocytopenic purpura, 1 of 5 normally pregnant women, 1 of 6 previously Rh-isosensitized pregnant women, and 9 other patients with a variety of disorders. Urinary L-chain paraproteins and abnormal k:λ ratios were present in 2 patients with CLL and 3 with LSC. Elevated urinary IgG excretion frequently accompanied elevated L-chain excretion. Albumin excretion was essentially normal in all patients. It is concluded that despite absence of clinical proteinuria, abnormal urinary L-chain and IgG excretion are frequently present in malignant lymphoid disorders, regularly present in infectious mononucleosis, and can be present in a variety of other immune-related diseases. Further work is needed to define more clearly the precise origin of urinary L-chain and the mechanisms governing its control before its full clinical value will be known.

Light chain deposition disease in kidney: A review of the literature

Light chain deposition disease is a rather uncommon monoclonal gammopathy with predominantly renal manifestations with presence of monoclonal light chains in serum and urine. It usually occurs in elderly male patients but can have a wide age range. Patients usually present with proteinuria and some renal dysfunction, but other organs like the liver and heart may also be involved and lead to the death of the patient. The survival of the patients is only about 18 months and benefit of renal transplantation in these patients is debatable, because of high chances of recurrence. Typical light microscopic diagnostic features are important to recognize this disease, which include mesangial nodules and thickening of tubular and glomerular basement membranes. Immunofluorescence shows a monoclonal pattern for kappa light chain, or much less commonly lambda light chain. Electron microscopy is further invaluable in identifying the granular deposits in the mesangial nodules and basement membranes. Keywords: Light chain deposition disease; Renal failure; Plasma cell dyscrasia; Immunofluroescence; Electron microscopy DOI: 10.3126/jpn.v1i1.4454 Journal of Pathology of Nepal (2011) Vol.1, 56-59

Isoelectric separation of urinary Bence Jones proteins and light chains of human IgG

Isoelectric separation of urinary Bence Jones proteins and light chains of human IgG

Isoelectric separation of urinary Bence Jones proteins and light chains of human IgG

Urinary Bence Jones proteins from three different myeloma patients and two preparations of light chains derived from normal, pooled human IgG either by oxidative sulfitolysis or reduction/alkylation were subjected to isoelectric separation in a vertical column containing a combined pH and density gradient. The Bence Jones proteins could be shown to be heterogeneous in pH gradients covering 0·5–7 pH units. In narrow pH gradients the resolving power was improved In pH gradients covering the range of pH 3–10 and in the presence of 5 M urea the light chain preparations could be partially resolved into the bands well-known from gel electrophoresis.