Bence-Jones protein, in urine

Monoclonal protein can be detected in serum, urine, or both in greater than 95% of patients with multiple myeloma (D16). Bone marrow plasma cells exceed 10%. Patients with advanced disease may excrete Bence-Jones proteins in urine. Both hypercalcemia and Bence-Jones proteinuria can contribute to renal failure (A6). 

A test for Bence Jones protein in urine. A few millilitres of urine are carefully placed onto concentrated hydrochloric acid. If Bence Jones protein is present, a layer of turbidity appears at the interface. The test has a false-negative rate of about 5%. False positives can occur if other proteins are present in large amounts, e.g. as in nephrotic syndrome. 

As indicated in Section I, the apparent mobility of a component under standardized experimental conditions is determined not only by the properties, concentration, and environment of that component but is also a function of the mobilities and concentrations of all the other components of the system. Thus the mobility of a Bence-Jones protein in urine may differ somewhat from that of the same Bence-Jones protein in blood plasma. Experiments in which urinary Bence-Jones proteins were added to normal serum, to be described, show that such environmental factors are probably responsible for the differences observed. 

Immunoglobulin fi agments in urine or serum in urine, usually Bence Jones protein in serum, occasionally other fragments, such as monomeric IgM or heavy chain fragments. 

Bundles, Coonrad, and Arends (R13) surveyed 35 patients with leukemia and detected paraproteins in at least 4, and possibly in 2 others. Since then there have been numerous reports of paraproteinemia with all kinds of lymphoma or leukemia, although almost no further surveys until 1969 when 19 of 76 patients were found to have excess light-chain excretion (L6). Personal surveys have revealed serum paraproteins in 3 atypical cases out of 124 consecutive patients with Hodgkin s disease, 26 of 207 with lymphosarcoma (see Section 7.7.2), 1 of 45 with reticulo-sarcoma, 0 of 31 with giant follicular lymphoma, 3 of 84 with chronic lymphatic leukemia, 0 of 43 with chronic myeloid leukemia, 0 of 57 with acute leukemia, and 1 of 5 with chronic monocytic leukemia as established by high lysozyme levels. Urine has revealed Bence Jones proteins in many of those with serum paraproteins and in addition only Bence Jones in 1 atypical Hodgkin s, 2 lymphosarcoma, 1 giant follicular lymphoma, yet 8 with chronic lymphatic leukemia. 

The ultracentrifuge has found comparatively little application to the study of pathological sera. McFarlane (235) obtained sedimentation diagrams of the sera in patients with tuberculosis, pneumonia, scarlet fever, multiple myeloma, ovarian carcinoma, and other disorders, but the results proved difiUcult to interpret. He found evidence of an increase in globuhns in some of the infections and in one case of myeloma noted a large fraction (probably not the X-protein), intermediate in sedimentation rate between the A and G components. Interesting results have been obtained in multiple myeloma (162, 178, 233, 235, 251, 271) in efforts to identify Bence-Jones proteins in the blood and urine. Whereas typical Bence-Jones proteins obtained from the urine (235, 251,... 

Blackman et al. (22) reported that the Bence-Jones protein in the urine of their case migrated with the mobility of /3-globulins, the major abnormal serum component also appearing as a large /3 peak. Malmros and Blix (231) foimd that the urinary Bence-Jones protein in the one case examined appeared to move with a mobility intermediate between /3- and y-globulins, the major abnormal serum protein component appearing as a large /3 peak. 

Kabat (251) was able to show by immunochemical methods that the main component of the serum of case 11 (Table VII) was, in fact, a Bence-Jones protein. Rabbit antiserum to this patient s urinary Bence-Jones protein gave a strong precipitin reaction with a 1 625 dilution of the patient s serum. This reaction appeared to be due entirely to Bence-Jones protein since after absorption of the rabbit antiserum with case 11 myeloma serum no additional precipitin reaction could be obtained with the patient s urine or purified Bence-Jones protein nor did the (absorbed) antiserum react with normal serum protein constituents. Qualitative dilution tests indicated a concentration of Bence-Jones protein in the serum of the same order of magnitude as was obtained for the main abnormal component by other methods. In case 1 (Table VII) Kabat was also able to demonstrate by immunochemical methods that while the main component was not a Bence-Jones protein, 0.15 to 0.2 gram per cent of a Bence-Jones protein nevertheless was present and could be identified and estimated by emplojdng the quantitative precipitin method. This concentration, approximately 1.5% of the total protein content of this serum, obviously could not be detected by salting-out, electrophoretic, or ultracentrifugal methods. 

Bence Jones proteins Light chain immunoglobulins found in the urine. 

It cannot be overemphasized that the absence of a monoclonal band of protein in the serum of a patient suspected of having multiple myelomatosis does not rule out the diagnosis. Quite frequently, the suspected patient may be excreting all the paraprotein in the form of a Bence Jones protein into the urine, and hence the simultaneous examination of both the serum and the urine by electrophoresis usually jirovides a rapid and excellent means of diagnosis. 

On examination of the urine and serum of numerous patients with suspected paraproteinemia in both Jamaicans and Africans between 1962 and 1966, it was concluded that whenever a low total serum y-globulin level with a normal serum electrophoretic pattern were encountered in a suspected case of multiple myelomatosis, it was then essential to obtain also a specimen of urine from such a patient for further electrophoretic examination. Invariably simultaneous electrophoresis of such sera and urines proved to be diagnostic, even when the classical heat test for Bence Jones protein was negative. Consequently it was found that concurrent electrophoresis of scrum and urine was the first means of detecting multiple myelomatosis in no less than 20% of the patients, which were subsequently confirmed either by bone marrow biopsy or X-ray examination or both (M3). 

Another crucial development was the finding that the BALB/c (Potter, 1972, 1977a) and later that the NZB strains of mice (Warner, 1975) when injected with paraffin oil develop a disease like multiple myeloma and also often excrete Bence Jones proteins. This not only provided an experimental model, but also permitted detailed comparison of mouse Bence Jones proteins and immunoglobulins with their human counterparts, an indispensable prerequisite for the study of antibody specificity. Relatively enormous quantities (kilograms in some instances) of Bence Jones proteins were obtainable from the urine of patients plasmapheresis yielded substantial quantities of myeloma proteins. Large amounts of the corresponding mouse proteins were also obtainable proteins from such neoplasms were in almost all instances monoclonal and homogeneous. 

The first tumor marker reported was the Bence Jones protein. Since its discovery in 1847 by precipitation of a protein in acidified boiled urine, the measurement of Bence Jones protein has been a diagnostic test for multiple myeloma (a tumor of plasma cells). More than 100 years after its discovery, the Nobel Prize-winning studies of Porter... 

While edema and redness of the uvula and soft palate were initially emphasized with y-chain disease, this sign has been found in other lymphoid neoplasia and is also not essential to y-chain. The y-chain has often been difficult to see on simple electrophoresis, and only a little enters the urine, in which Bence Jones protein has not been found. The y-chain exists as dimer, and represents mostly Fc (see Fig. 2) with some 8 or so amino acids of the Fd in front of it. The Fd seems quite untypical (F7) as if nonsense coding had resulted in a failure of most of it, so that no site is available for binding to light chains. As light chains seem to be not synthesized at all, presumably their coding has become completely nonsense or deleted. The molecular weights of such y-chains vary from 40,000 to 70,000. 

Bence Jones proteins (BJP), members of the paraproteins often found in the blood and urine of patients with multiple myeloma consisting of free light chains of immunoglobulins. 

---