The Bence-Jones protein (BJP) was described in 1962 as “free monoclonal light chains”, synthesized by a
single clone of B cells. Normal plasma cells appear to produce a slight excess of light chains, but B cell neoplasms may produce a much greater excess.
Once the mechanism of tubular reabsorption becomes saturated, BJPs are excreted in urine.
The molecular mass of BJP is quite variable; BJPs appear in urine as monomers (22 kDa), dimers (44 kDa), or low-molecular mass fragments (5–18 kDa), or show a high degree of polymerization.
The most frequent associations are with the following:
BJP determinations are useful in the following (3):
– bone pain, fatigue, recurrent infections, purpura, edema,
– unexpected hypogammaglobulinemia in adults, unexplained increased erythrocyte sedimentation rate, anemia, leukopenia, and thrombocytopenia, proteinuria
of polyclonal LCs in individuals with impaired tubular reabsorption.
Tests to be discouraged
– Inaccuracy of the methods in use to measure total protein in urine: these methods are often insensitive to microproteins in general and to BJP in particular.However, if the urine electrophoresis shows that BJP constitutes almost all urinary protein excretion, the determination of total urinary protein performed in the same laboratory by the same method at two points in time may provide useful indications regarding the efficacy of therapy;
– Different proteins can have different affinities for the dyes used to stain electrophoretic strips, and thus a lack of linearity of the densitometric response can be observed;
– Quite often multiple bands of BJP are present in the urine or the BJP co-migrates with other proteins, so that it is difficult to delimit the BJP peak correctly by densitometry.
It is suggested that follow-up of patients be performed in the same laboratory in order to minimize analytical variability.
– Antisera raised against a polyclonal mixture of LCs do not necessarily react in the same way with the monoclonal LCs of the sample;
– The molecular mass of BJP is quite variable; in urine, they appear as monomers (22 kDa), dimers (44 kDa), low molecular mass fragments, or can show a high degree of polymerization. The state of aggregation/ fragmentation of FLCs in urine is highly variable and unpredictable, depending on many. In addition, the antisera used for the quantification of FLCs are directed against epitopesthat are hidden in whole immunoglobulin molecules. In some severe conditions, such as AL, LC fragments of 5-18 kDa, comprising the amino-terminal region, are present in serum and urine and are the main constituents of amyloid fibrils. These pathogenic LC fragments can lack some or all relevant epitopes and be poorly recognized, or missed, by the antisera. All these factors can influence the immune reaction and may invalidate the calibration making the quantification of urinary monoclonal LC unreliable;
– The precision of the quantitative methods at the extremes of the dynamic range is poorly defined;
– There is no reference material for monoclonal LCs,and accuracy therefore remains an open problem;
– There is no standardization of the several methods available for the quantification of urine FLCs.