Benign paraproteinaemias.

A paraprotein can be defined in our present state of knowledge as a complete or incomplete immunoglobulin molecule, possibly abnormal, produced in excess by a single clone of immunocytes (Osserman and Fahey, 1968), and characterized on electrophoresis by a discrete band or peak. The discovery of a paraprotein in the plasma should not be regarded as synonymous with a malignant proliferative disease process and numerous authenticated cases prove that paraproteinaemia can be perfectly compatible with normal health. This was first noticed and reported by Waldenstrom in 1944 and has been confirmed since then by many observers. I shall use the term 'benign' paraproteinaemia to refer to this condition, ie, the occurrence of paraproteinaemia in the absence of detectable malignancy or other relevant pathology. Unfortunately some confusion has arisen owing to the wide variety of terms used to refer to this interesting but still ill understood and rather vaguely defined condition. A vast array of adjectives has been suggested and used by various authors, such as idiopathic, cryptogenic, rudimentary, lanthanic, discrete, sympton-poor, non-myelomatous, benign, coupled with nouns like monoclonal gammopathy, paraproteinaemia, dysimmunoglobulinaemia and dyscrasia. The paraprotein is detected primarily by electrophoresis of serum proteins on a suitable medium such as cellulose acetate which, if properly carried out, can detect small amounts of paraprotein. The clearest separation patterns on cellulose acetate are achieved by first diluting the serum sample 10-20 times followed by Nigrosin staining; this gives results comparable with those obtained by electrophoresis on agarose. Some authors advocate immunoelectrophoresis on the grounds that it will detect smaller amounts of paraprotein than simple electrophoresis, but this is controversial and the technique is impracticable for mass screening. Visual inspection of the electrophoretic strip seems to be perfectly adequate, particularly if carried out by two experienced observers. The electrophoresis technique should spread the gamma fraction adequately, with an overall protein separation of at least 4 cm. I do not consider the rapid techniques 77 which distribute the proteins over only 2 cm to be satisfactory (Kohn, 1973). Classification and typing of the paraprotein are performed by immunoelectrophoresis, using several dilutions of the serum sample to ensure optimal concentration of the paraprotein, thus avoiding prozone phenomena. For the detection of BenceJones protein in the urine a good electrophoretic technique using concentrated as well as unconcentrated urine is essential, and its presence is confirmed by immunoelectrophoresis with suitable light chain antisera.