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OBJECTIVE: Bence Jones proteinuria (BJP) refers to monoclonal free immunoglobulin light chains detected in urine, deriving from the clonal expansion of plasma cells in the bone marrow in patients with plasma cell dyscrasias, associated with monoclonal gammopathies of uncertain origin. This review summarizes routinely diagnostic procedures to assess BJP highlighting critical steps of preanalytical, analytical, and post-analytical phases.QUALITATIVE AND QUANTITATIVE METH-ODS: The best option for BJP detection is the first morning void urine sample and immunofixation electrophoresis detection technique (IFE) the recommended method, with the employment of specific polyvalent antisera. Other qualitative tests for a quick evaluation of BJP are currently available. Densitometric analysis per-formed on the 24-hour urine is the recommended method to quantify BJP. To overcome the 24-hour collection, it is possible to use morning urine sample and correlate the assessed value of BJP to creatininuria. In addition to the traditional ones, we here reviewed screening methods currently used to avoid false negatives and reduce the time around test (TAT), together with immunochemical quantification methods for in-creased sensitivity, after checking BJP by IFE. Mass spectrometry emerges as a new challenge in the determination of BJP.CONCLUSIONS: The employment of different based-assays methods may be useful for diagnostic purposes to improve the accuracy of BJP monitoring in monoclonal gammopathies.

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A 77-year-old man was admitted because of lumbago in 1989. Erythrocyte sedimentation rate was 75 mm/hour, hemoglobin 8.0 g/dl, white cell counts 2,400/mm³ without plasma cells, platelet counts 5.0×10⁴/mm³. Bence Jones proteinuria was demonstrated. Roentgenogram of skeleton revealed diffuse osteoporosis with oppression fractures of the thoratic and lumbar vertebrae. Immunoelectrophoresis revealed monoclonal Bence Jones (κ) M bow. Bone marrow smears showed 15.0% large and immature plasma cells. A diagnosis of multiple myeloma (Bence Jones κ) was made. During the next 28 days, leucocyte counts increased to 8,900/mm³ and plasma cell counts to 24.5%(2,181/mm³, respectively. A diagnosis of plasma cell leukemia was made. Plasma cells were proved in pleural effusions. Serum β₂ microglobulin increased to 18.4 μg/ml. In spite of administration of alkeran and prednisolone, he died of pneumonia one month after the onset of plasma cell leukemia.

A 77-year-old man was admitted because of lumbago in 1989. Erythrocyte sedimentation rate was 75 mm/hour, hemoglobin 8.0 g/dl, white cell counts 2,400/mm³ without plasma cells, platelet counts 5.0×10⁴/mm³. Bence Jones proteinuria was demonstrated. Roentgenogram of skeleton revealed diffuse osteoporosis with oppression fractures of the thoratic and lumbar vertebrae. Immunoelectrophoresis revealed monoclonal Bence Jones (κ) M bow. Bone marrow smears showed 15.0% large and immature plasma cells. A diagnosis of multiple myeloma (Bence Jones κ) was made. During the next 28 days, leucocyte counts increased to 8,900/mm³ and plasma cell counts to 24.5%(2,181/mm³, respectively. A diagnosis of plasma cell leukemia was made. Plasma cells were proved in pleural effusions. Serum β₂ microglobulin increased to 18.4 μg/ml. In spite of administration of alkeran and prednisolone, he died of pneumonia one month after the onset of plasma cell leukemia.

A 70-year-old woman was admitted to our hospital for close examination of massive proteinuria. Physical examination was negative ; normal blood pressure and no pretibial edema. Pertinent laboratory data revealed mild anemia, leukocytopenia and decreased levels of serum IgG, IgA and IgM. A 24-h urine collection contained 8.2g of Bence Jones protein (κ type) and 0.74 g of albumin. Bone marrow aspiratien revealed 48.4 % of atypical plasma cells. Bone destruction was not detected in the bone survey of either radiography or scintigraphy. She was diagnosed as having multiple myeloma (Bence Jones type) without bone involvement. Renal biopsy showed minor glomerular abnormalities and small foci of tubular atrophy and fibrosis. Neither amyloid deposition nor casts were observed. The patient is a rare case that was incidentally found to have multiple myeloma by urinalysis. One should be reminded of this case when an old patient has massive protemurla.

A Bence Jones protein isolated in the early 1960s from a patient (initials KWR) suffering from plasma-cell dyscrasia was crystallized and its structure was analyzed in four different unit cells by X-ray diffraction. The final models of the molecule in all crystal forms were virtually the same, although the elbow angles relating the constant and variable domains of the Bence Jones dimers varied over a range of 10 degrees. The tetragonal form had an R factor of 22.6% and an R(free) of 28.3% at 2.2 A resolution. Phosphate or sulfate ions (depending on the crystallization conditions) were found in the antigen-combining sites in all crystals, as well as an unidentified ligand tightly bound in the hydrophobic 'deep pocket' beneath the antigen-binding site. The ligand was treated as a phenol molecule. Two trigonal crystal forms were among those solved. One was grown at pH 4.0 and the other was only obtained after sitting for more than eight months at room temperature. The latter crystal was composed of molecules that were degraded in their constant domains. Both low pH and proteolytic degradation of constant domains are known to promote the polymerization of some Bence Jones proteins into amyloid fibrils. Indeed, in both trigonal crystal forms the molecules are organized with pseudo-hexagonal symmetry about the unique crystallographic axes in a manner suggestive of such fibrils. The arrangement of Bence Jones dimers is also consistent with other observations regarding Bence Jones amyloid-fibril structure and current models.

A Bence Jones protein isolated in the early 1960s from a patient (initials KWR) suffering from plasma-cell dyscrasia was crystallized and its structure was analyzed in four different unit cells by X-ray diffraction. The final models of the molecule in all crystal forms were virtually the same, although the elbow angles relating the constant and variable domains of the Bence Jones dimers varied over a range of 10 degrees. The tetragonal form had an R factor of 22.6% and an R(free) of 28.3% at 2.2 A resolution. Phosphate or sulfate ions (depending on the crystallization conditions) were found in the antigen-combining sites in all crystals, as well as an unidentified ligand tightly bound in the hydrophobic 'deep pocket' beneath the antigen-binding site. The ligand was treated as a phenol molecule. Two trigonal crystal forms were among those solved. One was grown at pH 4.0 and the other was only obtained after sitting for more than eight months at room temperature. The latter crystal was composed of molecules that were degraded in their constant domains. Both low pH and proteolytic degradation of constant domains are known to promote the polymerization of some Bence Jones proteins into amyloid fibrils. Indeed, in both trigonal crystal forms the molecules are organized with pseudo-hexagonal symmetry about the unique crystallographic axes in a manner suggestive of such fibrils. The arrangement of Bence Jones dimers is also consistent with other observations regarding Bence Jones amyloid-fibril structure and current models.

Four crystal forms have been grown and characterized by X-ray diffraction of a Bence-Jones protein collected from the urine of a multiple myeloma patient more than 40 years ago. Closely related tetragonal and orthorhombic forms belonging to space groups P4(3)2(1)2 and P2(1)2(1)2(1), with unit-cell parameters a = b = 68.7, c = 182.1 and a = 67.7, b = 69.4, c = 87.3 A, diffract to 1.5 and 1.9 A, respectively. Two closely related trigonal forms, both belonging to space group P3(1)21 with unit-cell parameters a = b = 154.3 A but differing by a doubling of the c axis, one 46.9 A and the other 94.0 A, diffract to 2.9 and 2.6 A resolution, respectively. The trigonal crystal of short c-axis length shows a positive indication of twinning. The trigonal crystal of longer c axis, which appeared only after eight months of incubation at room temperature, is likely to be composed of proteolytically degraded molecules and unlike the other crystal forms contains two entire Bence-Jones dimers in the asymmetric unit. This latter crystal form may shed some light on the formation of fibrils common to certain storage diseases.

Four crystal forms have been grown and characterized by X-ray diffraction of a Bence-Jones protein collected from the urine of a multiple myeloma patient more than 40 years ago. Closely related tetragonal and orthorhombic forms belonging to space groups P4(3)2(1)2 and P2(1)2(1)2(1), with unit-cell parameters a = b = 68.7, c = 182.1 and a = 67.7, b = 69.4, c = 87.3 A, diffract to 1.5 and 1.9 A, respectively. Two closely related trigonal forms, both belonging to space group P3(1)21 with unit-cell parameters a = b = 154.3 A but differing by a doubling of the c axis, one 46.9 A and the other 94.0 A, diffract to 2.9 and 2.6 A resolution, respectively. The trigonal crystal of short c-axis length shows a positive indication of twinning. The trigonal crystal of longer c axis, which appeared only after eight months of incubation at room temperature, is likely to be composed of proteolytically degraded molecules and unlike the other crystal forms contains two entire Bence-Jones dimers in the asymmetric unit. This latter crystal form may shed some light on the formation of fibrils common to certain storage diseases.

Two cases of prostatic cancer accompanied by monoclonal gammopathy of undetermined significance (MGUS) are reported. Both cases presented IgG-lambda type hyperimmunoglobulinemia and Bence Jones protein (BJP) in the urine. A characteristic of both cases was significant multiple bone metastasis, and one case also demonstrated a severe immunological disorder. During the treatment, one patient recovered from MGUS. We recommend that elderly male patients manifesting MGUS be examined for prostatic cancer.