Identification- and Quantification of Paraproteins

Identification (typing) of paraproteins

The detection of a paraprotein band must always be followed up with the specific typing of the band. It is important that the heavy and light chain components are identified because this confirms monoclonality and the paraprotein type may give the clinician additional information about the underlying tumour and prognosis. Electrophoretic pattern of a patient's sample may change during the course of their disease or treatment so the initial investigations can serve as a point of reference. Complete disappearance of the paraprotein is rare but is occurring increasingly with treatment regimens using high dose chemotherapy and bone marrow or stem cell transplantation. An oligoclonal-banding pattern is sometimes seen in patients after bone marrow transplantation and it is important to distinguish this from the original paraproteinaemia.

Quantification of serum paraproteins

Immunochemical quantification of paraproteins is unreliable. The densitometric scan ( HellabioScan ) of gel electrophoretic separation is recommended for measurement of paraprotein concentration. It is important to be aware that there is a differential dye binding between albumin and the globulins, therefore the most precise estimation of paraprotein is derived from the percentage of relative dye-binding of the paraprotein band compared with the total globulin fraction rather than the total protein. It is also important to note that there is a non-linear relationship between dye-binding and protein concentration at high paraprotein concentrations.

Measurement of serum total protein and albumin are generally reliable and it can be useful to use these two concentrations as a 'rough check' of the paraprotein quantitation. The albumin concentration added to the paraprotein concentration cannot exceed the total protein concentration and (accepting that there may be differential albumin to globulin binding) bands of similar areas should ultimately be of similar concentrations.

Quantification of Bence-Jones protein

Quantitation of BJP is being recommended as a criterion for response, progression of relapse of multiple myeloma treated by high-dose therapy and stem cell transplantation. This must be done like serum paraprotein quantitation, by densitometry of the urine electrophoresis and calculation of the paraprotein band with respect the urine total protein (either random or 24 hour).