Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0026764 (multiple myeloma)
 36,148 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

It has been shown previously that secretory IgA interacts with the mannose-specific lectin of Escherichia coli. The purpose of the study described here was to evaluate whether the N-linked oligosaccharide chains of the human IgA isotypes IgA1 and IgA2 differ in lectin receptor activity. A range of plant lectins specific for N-linked oligosaccharide chains were tested for their ability to precipitate IgA1 and IgA2 myeloma proteins, secretory IgA and free secretory component. IgA2 myeloma proteins reacted more strongly than IgA1 with the mannose-specific lectin ConA, whereas IgA1 myeloma proteins reacted more strongly than IgA2 with two galactose-specific lectins, Ricinus communis agglutinin I and Abrus precatorius agglutinin. This suggests that IgA2 possesses a larger proportion of short truncated complex type oligosaccharide chains and/or oligomannose type chains than IgA1. Further, IgA2 reacted more strongly than IgA1 myeloma proteins with Lens culinaris (lentil) lectin, and Pisum sativum (pea) lectin, suggesting that IgA2 exposes more of short, complex type chains fucosylated on the core than IgA1. The differences demonstrated in receptor activity between IgA1 and IgA2 may be important in their interaction with the microbial flora, as well with endogenous lectins, such as phagocyte receptors.
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PMID:Lectin receptors on IgA isotypes. 829 63

Assay of the activity of beta-1,4-galactosyltransferase (beta-1,4-GT) revealed that in addition to serum, milk, colostrum, amniotic and cerebrospinal fluids and malignant effusions, this enzyme is present also in tears and saliva. Molecular-sieve chromatography of human colostral whey and serum and subsequent assay of beta-1,4-GT activity have shown that beta-1,4-GT was present as a free enzyme (55 kDa) and associated with components of larger molar mass. The elution pattern did not change when the chromatography was carried out in a buffer devoid of, or enriched with, Mn2+, a cofactor of beta-1,4-GT activity. However, the activity associated with the large molar mass components was absent when the chromatography was carried out in the presence of a chelating agent (EDTA). Analyses of the eluted material by polyacrylamide gel electrophoresis in the presence of sodium dodecyl sulfate (SDS-PAGE), and by immunodiffusion indicated that the major colostral component in beta-1,4-GT activity-containing fractions was secretory IgA (S-IgA); in addition, the beta-1,4-GT activity was detected in fractions that contained lactoferrin and alpha-lactalbumin. Interactions of beta-1,4-GT with S-IgA and lactoferrin in colostrum were also demonstrated by the detection of radioactivity in precipitin lines obtained by immunoelectrophoresis and autoradiography of the colostral whey after it had been incubated with UDP-[3H]-galactose. Furthermore, radioactively labeled S-IgA and alpha-chain were detected when colostral whey incubated with UDP-[3H]-galactose was analyzed by SDS-PAGE under non-reducing and reducing conditions, respectively. In serum, the beta-1,4-GT-binding components identified in fractions after molecular-sieve chromatography were IgG, IgA, IgM and transferrin. The binding of beta-1,4-GT to immunoglobulins (Ig) was also demonstrated by assaying the beta-1,4-GT activity associated with Sepharose-4B-immobilized Ig of various isotypes and molecular forms, which were incubated with colostral beta-1,4-GT in the presence of Mn2+. Beta-1,4-GT measured by enzyme activity was bound to these Ig in order: polymeric IgA2 > monomeric IgA1 = polymeric IgA1 = secretory IgA = pentameric IgM > IgG. Immobilized component chains, namely alpha, mu and J chains, bound beta-1,4-GT more effectively than native Ig. Incubation of the IgA1 myeloma protein with crude human colostral galactosyltransferase in the presence of UDP[3H]-galactose and Mn2+ resulted in galactosylation of both N- and O-linked carbohydrate side chains.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Interactions of galactosyltransferase with serum and secretory immunoglobulins and their component chains. 843 6

A human monoclonal IgA1-IgA2 lambda hybrid molecule was detected in a myeloma patient homozygous for the A2m(1) allotype during a systematic study of monoclonal IgA with subclass-specific monoclonal antibodies (mAb) and the lectin jacalin. This monoclonal immunoglobulin (GAU) reacted with both, although not with all, anti-alpha 1 and anti-alpha 2 mAb. Its heavy (H) chain contained an alpha 1 hinge region as shown by jacalin reactivity, the presence of disulfide-linked H and light chains in spite of its belonging to the IgA2m(1) allotype and amino acid composition of the isolated hinge region. The complete sequence of the H chain was deduced from that of complementary DNA clones from bone marrow cells. The CH1 domain, hinge region and beginning of the CH2 domain and the membrane peptide were encoded by the alpha 1 gene, with an insertion of an alpha 2m(1) gene sequence accounting for the end of the CH2 and part or all of the CH3 domain (sequence identity between the two normal genes precludes a precise definition of breakpoints). The region of the 5' recombination site included a repeat of a six base pair sequence which might play a role in the genetic exchange. The GAU hybrid alpha gene was undetectable in the patient's genomic DNA from polymorphonuclear cells. The genetic event which occurred at the level of the proliferating plasma cell clone is most likely to be a gene conversion.
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PMID:A human myeloma IgA with a hybrid heavy chain resulting from putative somatic gene conversion. 843 72

The structural features of the human IgA1 tailpiece required for interaction with J chain in IgA dimer assembly were investigated using a protein engineering approach. Wild-type and mutant forms of IgA1 were expressed in the mouse myeloma cell line, J558L, which endogenously expresses J chain. Wild-type IgA1 was secreted as a mixture of dimers and monomers. Deletion of the entire tailpiece by stop codon introduction completely prevented dimer formation. Similarly, substitution of the penultimate residue of the tailpiece, Cys471, with serine resulted in the secretion of IgA monomers alone. Substitution of Asn459 with alanine to prevent attachment of N-linked carbohydrate to the tailpiece also resulted in markedly reduced dimer assembly. These results indicate the critical role played by the tailpiece, and Cys471 in particular, in IgA dimerization. In addition, we found tailpiece-deleted IgA1 and the Cys to Ser471 mutant IgA1 were secreted as mixtures of covalently associated monomers (alpha 2L2) and alpha L half-molecules. The tailpiece may thus play some role in promoting the association of alpha-chains required for IgA monomer assembly.
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PMID:Mutagenesis of the human IgA1 heavy chain tailpiece that prevents dimer assembly. 868 9

In our previous study, gas-phase hydrazinolysis was used to analyze the glycoform of the O-linked oligosaccharide of human serum IgA1. All O-linked oligosaccharide chains are known to be present in the hinge portion. However, the number of O-linked oligosaccharide chains on IgA1 remained unclear. In order to determine the number of linked sugar chains, we applied matrix-assisted laser desorption ionization time-of-flight mass spectrometry (MALDI-TOFMS) to the hinge glycopeptide prepared from human serum IgA1. MALDI-TOFMS did not show clear peaks, probably due to the microheterogeneity of the structure of each sugar chain. However, elimination of peripheral sialic acid and galactose residues by sequential treatment with neuraminidase and beta-galactosidase gave clear mass spectra with several sharp peaks. On the basis of these spectra, we conclude that IgA1 prepared from normal human serum carries different numbers of sugar chains. There are two major populations, one contains five GalNAc residues and the other four GalNAc residues. On the other hand, the hinge glycopeptide prepared from myeloma IgA1 was composed mainly of one population containing four GalNAc residues. Earlier, we reported incomplete glycosylation of IgA1 isolated from the serum of an IgA1 myeloma patient. In this experiment, the presence of four O-linked oligosaccharides per heavy chain of IgA1 from a myeloma patient was found. The reason why only four out of five sites on the hinge glycopeptide were fully glycosylated in the IgA1 from the IgA1 myeloma patient is not clear.
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PMID:Estimation of the number of O-linked oligosaccharides per heavy chain of human serum IgA1 by matrix-assisted laser desorption ionization time-of-flight mass spectrometry (MALDI-TOFMS) analysis of the hinge glycopeptide. 888 26

Actinomyces naeslundii and Streptococcus gordonii, oral bacteria that possess Gal/GalNAc- and sialic acid-reactive lectins, respectively, were adherent to immobilized secretory immunoglobulin A (IgA) and two IgA1 myeloma proteins but not to two IgA2 myeloma proteins. Apparently, O-linked oligosaccharides at the hinge region of the IgA1 heavy chain are receptors for lectin-mediated adhesion of these bacteria.
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PMID:Recognition of immunoglobulin A1 by oral actinomyces and streptococcal lectins. 894

In this paper, the authors report the use of liquid-liquid partition chromatography (LLPC) in an aqueous polyethylene glycol (PEG)/dextran two-phase system to compare the surface properties (partition properties) of human antibodies and fragments thereof. The surface properties of all the monoclonal antibodies of different classes and subclasses investigated were within the same broad range as that observed for the polyclonal antibodies and no relationship was found between the exposed surfaces of the immunoglobulins (Ig) and their heavy chain isotype. Moreover, Fc fragments from various IgG1, 2 and 4 myeloma proteins were found to exhibit similar surface properties. Employing chimeric antibodies with identical variable regions the authors found that intact IgG1, 2 and 4 displayed identical surface properties, while the corresponding IgA1, IgA2, IgG3, IgE and IgM antibodies differed both from each other and from the IgGs. The surface properties of chimeric IgG3 could be made similar to those of the IgG1, 2 and 4 chimers by partially reducing the length of the hinge section, but new differences in surface properties appeared when their hinges were of similar length. Thus, LLPC can be used to detect differences or similarities in the surface properties of the antigen-binding regions as well as the Fc part in the various isotypes. This can shed light on biological activities such as antigen binding and effector function.
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PMID:Comparison of surface properties of human IgA, IgE, IgG and IgM antibodies with identical and different specificities. 894 93

A study was conducted to investigate the relationships between the characteristics of IgA paraprotein and the clinical findings in a group of 196 patients. In 19 cases IgA paraprotein was associated with another monoclonal immunoglobulin (IgG or IgM); the other 177 patients had a single IgA paraprotein; 145 of them corresponded to multiple myeloma (MM) and the other 32 to other diagnostics. Class and type of paraproteins were identified by immunoelectrophoresis and subclass by an enzyme-immunoassay specifically developed for this study. The degree of polymerization of the protein was determined by gel filtration; quantitation of monoclonal IgA and polyclonal IgG and IgM was obtained by kinetic nephelometry. Out of 196 paraproteins, 96.4% were classified in IgA1 subclass and only 3.6% in IgG2. In 14 cases, all of them diagnosed with MM, monoclonal IgA in serum was associated with Bence-Jones protein; in more than 78% of them light chains corresponded to type lambda, whereas type kappa predominated (over 60%) in cases without Bence-Jones protein in serum. Significantly higher serum levels of monoclonal IgA were associated with the diagnosis of myeloma, with type kappa paraproteins, and with the presence of Bence-Jones protein in serum. The cases with two paraproteins (IgA and IgG or IgM) had significantly lower serum levels of IgA, with comparable levels of total paraprotein (the addition of both monoclonal immunoglobulins). Serum levels of polyclonal IgG and IgM, which appeared decreased in cases of MM, were normal in cases with other conditions. In all these cases, monoclonal IgA showed a monomeric character, whereas relevant amounts of polymerized IgA paraprotein was found in almost a third part of myeloma cases, particularly in those with higher serum levels of paraprotein, or when paraprotein belonged to type kappa. The 5 IgA2 paraproteins analyzed had a polymeric character. In conclusion, a detailed, both qualitative and quantitative, analysis of IgA paraproteins can lead to a better knowledge of conditions associated with their presence and at the same time provides useful data for a clinical evaluation of patients.
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PMID:[Isotypic characterization of IgA paraproteins: association with other clinical and analytic data]. 898 39

IgA1 Abs possess conserved N-linked glycosylation sites in the second C region and secreted tailpiece domains. To understand the role of these carbohydrates in the structure and function of human IgA1, site-directed mutants that produce human IgA1 lacking either one or both of the N-linked carbohydrate sites have been produced. When the mutant heavy chains are expressed in myeloma lines producing the relevant kappa-light chain, efficient secretion of the monomer and dimer forms of IgA1 is seen. In addition, higher polymer forms of the IgA molecules lacking the third domain carbohydrate, either singly or in the double mutant, are present. Functional analysis of the IgA1 proteins has shown significant differences between the various mutants and wild-type IgA. The carbohydrate mutants show a reduced affinity for their target Ag, dansyl. All of the IgA1 molecules retained the ability to bind to the polymeric Ig receptor. C3 binding was observed for all of the IgA molecules, with the IgA mutants lacking the third domain carbohydrate showing a reduced ability to bind C3; however, IgA did not effectively activate the alternative pathway, as determined by factor B cleavage and terminal complex binding. These studies demonstrate that N-linked glycosylation in the constant domain of human IgA1 plays an important role in the biologic properties of IgA1.
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PMID:Elimination of N-linked glycosylation sites from the human IgA1 constant region: effects on structure and function. 899 88

Tonsils were obtained by tonsillectomy from a 33-year-old woman with IgA nephropathy. Hetero-hybridoma cells of human tonsillar B-lymphocytes with mouse myeloma cells (NS-1) were made, and cultured in HAT medium supplemented with 10% fetus bovine serum and hybridoma cloning factor. The culture medium was analyzed by Western blot analysis using anti-human IgA antibody, and both IgA1 and IgA2 were demonstrated to be produced. The specimens of the biopsied kidney tissue of IgA nephropathy were washed with 0.02 M citrate buffer (pH 3.2) to remove deposited IgA from glomerulus. The specimens were then incubated with the culture media of hybridoma cells, and immuno-fluorescence analysis using FITC-conjugated anti-human IgA antibody was performed. IgA deposit was efficiently removed by washing with citrate buffer and was recovered after incubation with the culture medium of hybridoma cells. Direct evidence of binding of IgA produced by tonsillar B-lymphocytes to the glomerular mesangium of IgA nephropathy was demonstrated.
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PMID:Direct evidence of the production of IgA by tonsillar lymphocytes and the binding of IgA to the glomerular mesangium of IgA nephropathy patients. 908 76


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