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.

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.

'Incomplete' pyroglobulin-gamma disease in a patient with osteosclerotic myeloma.

A 50-year-old female, heterozygous for beta-thalassaemia was found to have a lytic lesion surrounded by osteosclerotic tissue in the 1st lumbar vertebra. Aspiration of the lesion showed 100% atypical plasma cells. The bone marrow contained 17% myeloma cells. Despite normal electrophoresis and immunoelectrophoresis of serum and urine, 'rouleaux' formation was pronounced. Treatment of the serum sample with 2-mercaptoethanol and heat (56 degrees C) disclosed an uncommon pyroglobulin. Analysis of the ammonium sulphate precipitate of the serum by sodium-dodecyl-sulphate polyacrylamide gel electrophoresis revealed a 43 kD component with higher anodic mobility than normal gamma chains. Ultrafiltration column chromatography of the serum revealed a narrow spike of approximately 4 S that contained gamma heavy chain antigenic determinants in addition to normal 7 S IgG.

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%).

Concomitant association of pyroglobulinemia and cryoglobulinemia in 2 patients in multiple myeloma.

We have reported two cases of multiple myeloma associated concomitantly with pyroglobulinemia and cryoglobulinemia. One of them showed blood picture of plasma cell leukemia. Plasma cell leukemia with two abnormal serum proteins at the same time, has not been reported yet to our knowledge. In that case, the large amounts of plasma cells were detected in the urine sediment.

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.

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.