3. The laboratory investigation of monoclonal gammopathies.

The monoclonal gammopathies are a group of disorders characterized by proliferation of a single clone of plasma cells that produce a homogeneous, monoclonal (M) protein. The structure of immunoglobulins, relationship of normal (polyclonal) immunoglobulins to myeloma and macroglobulin (monoclonal) immunoglobulins, pattern of monoclonal immunoglobulin overproduction, and laboratory methods for the recognition and study of monoclonal proteins in the serum and urine are reviewed. Interpretation of these laboratory tests is emphasized. The demonstration of a monoclonal protein in the serum or urine of a patient suggests multiple myeloma or one of its variants (solitary plasmacytoma of bone, extramedullary plasmacytoma, or plasma cell leukemia); Waldenström's macroglobulinemia or, occasionally, lymphoma; heavy-chain diseases (gamma, alpha, and mu); primary amyloidosis; and monoclonal gammopathies of undertermined significance. The electrophoretic and immunoelectrophoretic patterns found in the monoclonal gammopathies are discussed. Periodic electrophoresis of the serum and urine is essential in the follow-up and management of patients with a monoclonal gammopathy.

IgE pyroglobulinemia in multiple myeloma.

A new case of IgE/K myeloma in a 38-year-old male is described. The clinical course, bone marrow picture and serum electrophoretic pattern were typical of multiple myeloma. Heating of the serum at 56 degrees C induced an irreversible gel formation or pyroglobulin that was isolated and proved to be identical to the IgE paraprotein, by biochemical and immunochemical methods. The thermoprecipitability was abolished by treatment with urea, sodium dodecyl sulphate and neutral salts and not inhibited by sugars, alcohols, 2-beta-mercaptoethanol and guanidine HCl. The association of an IgE myeloma protein with a pyroglobulin is a finding not previously reported in a myeloma of this class.

Immunochemical characterization of monoclonal protein in the serum of a patient with Waldenstr]om's macroglobulinemia showing both pyroglobulin and cryoglobulin properties.

A patient with Waldenstr]om's macroglobulinemia whose serum demonstrated properties of both pyroglobulin and cryoglobulin was studied. A monoclonal (M) protein in the serum of the patient was identified by immunoelectrophoresis (IEP) and immunofixation electrophoresis (IFE) as IgM-lambda. The M-protein was separated by gel permeation high-performance liquid chromatography (HPLC). Cryoglobulin in the serum was isolated by the method of cold precipitation. The cryoglobulin was identified as IgM-lambda type by IEP and was the same M-protein as that which occurred in this patient's serum. The purified cryoglobulin also had the properties of a pyroglobulin. Neither property disappeared following pretreatment with 2-mercaptoethanol (2-ME), urea, and Triton X-100 detergent, and deglycosylation with N-glycanase (E.C. 3.5.1.52). We suggest that these abnormal properties were caused by the molecular abnormality of the IgM-lambda M-protein.

Monoclonal cryoglobulins and pyroglobulins.

In a series of 1182 monoclonal Ig, the authors demonstrated 10 cases with monoclonal cryoglobulin (0.8%) and 5 cases with pyroglobulin (0.42%) in the serum; in two of these cases both thermoproteins were present simultaneously. One observation revealed mixed cryoglobulin consisting of monoclonal IgM-kappa and polyclonal IgG. In 70 Waldenström's macroglobulinemias, monoclonal cryoglobulin occurred in 10%, pyroglobulin in 5.71%. In a subgroup of 744 monoclonal IgG, monoclonal cryoglobulin was demonstrated in 3 cases (0.4%), pyroglobulin in one case (0.13%).

[Study of amino monosaccharides by thermoionic detection in gas-liquid chromatography. Application to a pyroglobulin IgM (author's transl)]. / Etude des monosaccharides aminés par détection thermoionique en chromatographie gaz-liquide. Application à une pyroglobuline IgM.

The monosaccharides of proteic samples liberated by methanolysis and submitted to trimethylsilylation by the trimethylsilylimidazole (TSIM) are determined by gas-liquid chromatography. The neutral sugars are detected in simple flame ionization (FID) and the amino sugars identified separatively by the use of a thermoionic detector (TID) which responds selectively to nitrogenous and phosphorated compounds. The method described has been tested on standard mixtures of monosaccharides and on a well known glycoprotein : the uromucoid. Then it has been applied to a pyroglobulin IgM (mu2, chi2).

IgG-cryoglobulin consisting of both kappa and lambda light chains and beta 1C/1A.

A 72-year-old woman was diagnosed as multiple myeloma. Her plasma contained IgG-cryoglobulin consisting of both kappa and lambda light chains and beta 1C/1A. Such unique cryoglobulinemia has been reported in 2 cases in the literature, but never in Japan.