Increased sialylation of oligosaccharides on IgG paraproteins--a potential new tumour marker in multiple myeloma. (1/110)

AIMS: To investigate whether changes in carbohydrate structure of IgG are related to malignancy and stage of disease in myeloma and monoclonal gammopathy of uncertain significance (MGUS). METHODS: 61 patients were studied at diagnosis: 14 with MGUS, nine with stage I multiple myeloma, 11 with stage II, 21 with stage III, and five with solitary plasmacytoma. IgG was extracted from serum by protein G affinity chromatography. Oligosaccharides were cleaved from the protein backbone enzymatically by N-glycosidase F. Oligosaccharide analysis was performed by high pressure anion exchange chromatography with pulsed electrochemical detection (HPAE-PED). RESULTS: Up to 15 oligosaccharide peaks were identified in three major fractions: neutral, monosialylated, and disialylated. Patients with myeloma showed an increase in the proportion of sialylated oligosaccharides in comparison with patients with MGUS. The ratio of neutral to sialylated oligosaccharides (N:S) was reduced at all stages of myeloma compared with MGUS: MGUS, 11.35; myeloma stage I, 7.6 (p = 0.047); stage II, 5.20 (p = 0.035); stage III, 3.60 (p = 0.0002); plasmacytoma, 7.5 (p = 0.046). The N:S ratio was independent of paraprotein concentration (r = 0.05). CONCLUSIONS: The ratio of neutral to sialylated oligosaccharides may act as a new marker of malignancy in IgG paraproteinaemia and warrants further investigation.  (+info)

Gamma heavy chain disease in man: translation and partial purification of mRNA coding for the deleted protein. (2/110)

Lymphoid cells obtained from the peripheral blood of a patient with heavy chain disease have been established in long-term culture. They continue to produce a protein antigenically identical to the deleted gamma3 heavy chain disease protein found in the patient's serum. The availability of the cell line has made it possible to analyze the mRNA coding for this protein. The primary in vitro translation product is 1500-2000 daltons larger than the polypeptide portion of the cytoplasmic or secreted protein and has methionine at the amino terminus. The mRNA sediments at 15.5 S on sucrose gradients and therefore appears to be smaller than the 17S message coding for normal-sized mouse gamma chains. It contains a base sequence that codes for a hydrophobic amino-terminal peptide not found in the cytoplasmic protein. There was no evidence for the synthesis of translatable light chain message by these cells. The present data suggest that this protein results from a primary somatic genetic event that gave rise to a cell product bearing a normal aminoterminus sensitive to limited proteolytic digestion. The serum protein thus appears to begin in the hinge region but, in fact, contains a normal heavy chain initiation site.  (+info)

Remission of inflammatory arthropathy in association with anti-CD20 therapy for non-Hodgkin's lymphoma. (3/110)

We describe a case involving a 53-yr-old male with a marginal zone B-cell lymphoma, associated with an IgM paraprotein and a rheumatoid factor-negative inflammatory polyarthropathy, treated with monoclonal anti-CD20 antibody. During the subsequent 12 weeks, evidence of synovitis reduced to a negligible level, despite no significant change in lymphoma bulk or paraprotein level. The relationship between the lymphoma and the arthropathy, and the likely mechanism of remission of the arthropathy, are discussed in the context of the potential value of anti-CD20 therapy in rheumatoid arthritis.  (+info)

Monomeric complement-activating IgG paraproteins. (4/110)

Three patients presented a unique syndrome of recurrent panniculitis with an IgGkappa paraprotein and depletion of the early components of the classical pathway of complement. The IgGkappa paraproteins were monomers with a normal structure, and with no evidence for aggregation, as assessed by electron microscopy and ultracentrifugation. Both heavy and light chains were of normal molecular size (SDS-PAGE), and the paraproteins were not heavily glycosylated. However, the paraproteins from all three patients had unusual features that included abnormal behavior on gel filtration chromatography and a heavy chain of high pI. When analyzed by fast protein liquid chromatography (Superdex 200), elution of the paraproteins was retarded, particularly when the ionic strength was increased. This retardation was partially reversed in 20% alcohol, and fully reversed in 6 M guanidine-HCl. Neither anti-C1 inhibitor nor anti-C1q autoantibodies were found in any of the patients' sera. However, the paraproteins bound to the globular heads of C1q at normal ionic strength. They activated C4 in normal human serum, but not in C1q-deficient serum. Activation led to the formation of C1s-C1 inhibitor complexes. Taken together, the data suggest that the unusual paraproteins have the capacity to bind C1q, which then leads to activation of C1. The ability of these paraproteins to activate C1, in spite of their being soluble monomers, is likely to be related to their unique physicochemical features.  (+info)

Paraprotein estimation: a comparison of immunochemical and densitometric techniques. (5/110)

Paraproteins have been estimated by both immunochemical methods and densitometric analysis of electrophoretic strips. Correlation between the results obtained by these two methods, although generally good for assessing trends, varied between patients.  (+info)

Identification of the paraproteins and clinical significance of more than one paraprotein and clinical significance of more than one paraprotein in serum of 56 patients. (6/110)

Sera from 56 patients with more than one paraprotein were investigated for immunoglobin class and light chain type of each paraprotein. The patients were divided into two groups according to the diagnosis, that is myeloma and macroglobulinaemia or others. The frequency of combinations of paraproteins was considered in the whole series and in the two groups. The laboratory and clinical findings were analysed to investigate the diagnostic and prognostic significance of more than one paraprotein in a serum. It is concluded that a lower percentage of patients with more than one paraprotein can definitely be shown to have myeloma than might be expected from studies on monoclonal paraproteinaemia, that patients having IgA paraproteins in the serum had the poorest prognosis, and that paraproteins with lambda light chains were more likely to be associated with myeloma or macroglobulinaemia. A discriminant analysis of ESR and total paraprotein levels in the two groups of patients showed that combinations of the two parameters were not more effective at distinguishing the groups than the ESR alone.  (+info)

Bcl-2 rearrangement in patients with chronic hepatitis C associated with essential mixed cryoglobulinemia type II. (7/110)

Hepatitis C virus (HCV) infection is found in 80% to 90% of patients with essential mixed cryoglobulinemia (EMC) type II, which is associated with monoclonal IgMk produced by monoclonal B cells. It was investigated whether bcl-2 rearrangement is associated with the clonal B-cell proliferation of EMC induced by hepatitis C. The study groups were composed of 15 patients with HCV and EMC, 12 patients with HCV without EMC, and 7 patients with chronic liver disease (CLD) unrelated to HCV. Fluorescence in situ hybridization with probes was applied to JH and to bcl-2 to study whether JH/bcl-2 translocation was present in these patients. Thirteen of 15 (86%) of patients with HCV-related EMC had the JH/bcl-2 translocation, a significantly higher rate than in HCV patients without EMC (16%; P < .001). Bcl-2 rearrangement was not detected in the patients with CLD not related to HCV. The JH/bcl-2 translocation may constitute a pathogenetic link for the development of NHL in patients with HCV infection. (Blood. 2000;96:2910-2912)  (+info)

A paraprotein in severe combined immunodefeciency disease detected by immunoelectrophoretic analysis of plasma. (8/110)

A qualitative study was made of the plasma immunoglobulins of a child with severe combined immunodeficiency. By immunoelectrophoresis an immunoglobulin with an abnormal electrophoretic mobility was detected. This protein possessed mu heavy chain determinants, gave no detectable reaction with antisera specific for light chains, was of a relatively small molecular size, and was probably not composed of subunits held together by easily reduced disulfide bonds. The light chains that were present in this patient's plasma had a homogeneous electrophoretic mobility. The patient's plasma also contained at least two other immunoglobulins whose antigenic identity could not be established. One of these was abnormal in its electrophoretic mobility. The presence of the abnormal protein with mu determinants in the plasma of the second unrelated child with a similar disease suggests that the detection of this protein may have implications for the diagnosis or classification of immunodeficiency diseases.  (+info)