Electrophoretic characterization of a gamma-1-heavy chain disease.

This report describes a new case of gamma-1-heavy chain disease found in a woman with malignant lymphoproliferative disease. The patient's serum and urine containing gamma-1-heavy chains were analyzed using different electrophoretic approaches, especially two-dimensional electrophoresis and immunoblotting analysis. In a serum sample, five sets of gamma-1-heavy chain spots differing in molecular weight with acidic pI values and one set of more basic gamma-1-heavy chain spots were found. The major group of spots exhibited molecular weight in the range from 29 to 39 kDa. Examination of urine sample proved the presence of the more basic set of gamma-1-heavy chain spots and two acidic groups, including 29 to 39 kDa set.

Free fragments of gamma chain in the urine. A possible source of confusion with gamma heavy-chain disease.

With currently used microconcentrators, high-resolution electrophoresis, and immunofixation electrophoresis, relatively homogeneous free fragments of gamma chain (FFGC) unaccompanied by light chains, which cannot be found in the serum, may be discovered in the alpha-2 region during routine examination of the urine. The urinary alpha-migrating FFGC is of no apparent clinical significance and should not be confused with the antigenically related FFGCs of gamma heavy-chain disease. In gamma heavy-chain disease, the FFGCs are often demonstrable in the urine, but are always present in the serum and migrate in the beta-gamma region.

[Gamma-1 heavy chain disease with the demonstration of Bence-Jones proteins]. / Gamma-1-Schwerkettenkrankheit mit Nachweis von Bence-Jones-Proteinen.

We describe a 61-year-old patient suffering from gamma-1-heavy-chain disease (gamma 1-HCD) associated with Bence-Jones-lambda proteinemia and proteinuria. The analysis of the patients gamma 1-HCD protein (WIN) shows a deletion of the complete Fd fragment. The N-terminal seven amino-acid residue does not resemble any of the known immunoglobulin-heavy-chain variable regions. Unexpectedly, in PBL-DNA and in DNA from EBV-immortalized cells we found in addition to the expected predominantly rearranged Ig-lambda-light-chain gene a predominant rearrangement of an Ig-kappa gene. These findings show that the gamma-1-heavy-chain disease of the patient involves a defective regulation of Ig-light-chain-gene activation as well.

Immunoselection screening methods for detection of the free heavy chains.

Immunoselection screening methods were developed for the detection of the free heavy chain determinants of biological fluids. The optimal sensitivity range of the electrosyneresis and electroimmunoassay type methods lies between 400 ng and 2 micrograms/ml and between 3 micrograms and 1 mg/ml for immunoglobulins. The sensitive, relatively rapid and cheap variants of the procedure are suitable for the detection of "heavy chain diseases" and of heavy chain fragments.

Rheumatoid arthritis associated with transient gamma 2-heavy chain disease.

This paper describes the clinical history of a patient (F.-O.) with longstanding rheumatoid arthritis (RA), who subsequently developed a transient gamma 2-heavy chain disease (gamma 2-HCD). Immunochemical studies comprised serial determinations of serum levels of intact IgG, the gamma-HCD protein, IgA, and IgM. New applications of the rocket immunoselection and the radial immunodiffusion were used for the quantitation of the gamma-HCD protein and intact IgG, respectively, in the presence of one another. Immunofluorescent microscopy on bone marrow cells showed cells containing gamma-heavy chains but devoid of light chains. Protein studies of the isolated gamma-HCD protein revealed a molecular weight of 72 000 in the dimeric form, a carbohydrate content of 9.7%, and a PCA-Val-Gln NH2-terminal amino acid sequence. The literature on the rare coexistence of RA and gamma-HCD in a single patient is reviewed.

Biochemical findings in a case of mu-chain disease.

We report the 16th case of mu-chain disease. Unlike most previously reported cases, free mu-chains, but not Bence Jones protein, were present in the urine. The usefulness of immunofixation as a means of detecting free heavy chains in the serum is demonstrated.

Studies on the glycopeptides isolated from the urinary protein in heavy-chain disease.

The urinary protein excreted in heavy-chain disease was separated by ion-exchange chromatography into two broad fractions designated Cra-1 and Cra-2. For a dimeric molecular weight of approx. 51000, Cra-1 contained 3-4 residues of 6-deoxy-l-galactose (l-fucose), 10 of d-mannose, 5-6 of d-galactose, 12 of 2-acetamido-2-deoxy-d-glucose (N-acetyl-d-glucosamine) and 4-5 of N-acetylneuraminic acid (sialic acid), whereas the corresponding values for Cra-2 were 2, 10, 7, 12 and 7. Cra-2 contained in addition 1 residue of 2-acetamido-2-deoxy-d-galactose (N-acetyl-d-galactosamine). Cra-1 contained an average of four oligosaccharide units, two of which contained 1 residue of 6-deoxy-l-galactose, 3 of d-mannose, 1 of d-galactose and 3 of 2-acetamido-2-deoxy-d-glucose, whereas the other two units contained the same proportions of 6-deoxy-l-galactose, d-mannose and 2-acetamido-2-deoxy-d-glucose but 2 residues of d-galactose and 2 of N-acetylneuraminic acid. Cra-2 also contained an average of four oligosaccharide units, but the range of glycopeptides was much wider, containing 0-1 residue of 6-deoxy-l-galactose, 2-3 of d-mannose, 2-3 of d-galactose, 2-3 of 2-acetamido-2-deoxy-d-glucose and 1-3 of N-acetylneuraminic acid. Possible reasons for this heterogeneity are discussed. Glycopeptides were also isolated from Cra-2 that contained 1 residue of d-mannose, 2 of d-galactose, 1 of 2-acetamido-2-deoxy-d-galactose and 0-3 of N-acetylneuraminic acid.