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)

The specificity of five monoclonal anti-IgE antibodies (Mabs) was studied in direct latex agglutination and agglutination-inhibition experiments by particle-counting immunoassay. Twenty IgE myeloma proteins and several purified D epsilon O-, D epsilon 2-containing pepsin and papain fragments of IgE-DES(kappa) were used in the evaluation. The results demonstrate two Mabs with isotypic specificity for two distinct epitopes of the Fc epsilon-fragment within the D epsilon 1- and D epsilon 2-determinants. One Mab recognized only the immunizing IgE protein and was directed against determinants on the Fd epsilon-fragment probably related to the idiotype. Anti-Em(1) allotypic Mabs recognized all 20 IgE myeloma proteins including two of Japanese origin and the Em(1)-allotype was confined to D epsilon-determinants. Interestingly, one Mab (ALE) reacted with all 8 IgE myeloma proteins of the lambda light-chain type but none out of 12 bearing kappa chains. ALE seems therefore to recognize a new marker on IgE besides the known idiotypic, allotypic and isotypic ones. These results illustrate that a critical specificity control of Mabs is always warranted. Moreover, one should be aware of possible interference in IgE assays from the kind of determinants recognized by ALE whenever intact IgE myeloma proteins are used to raise polyclonal antisera, to get immunosorbent-purified anti-IgE antibodies or when used as tracers and standards.
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PMID:Monoclonal antibodies against human IgE. Identification of a determinant restricted to IgE of the lambda light-chain type. 242 45

We report on the natural occurrence of human serum antibodies with specificity for a human monoclonal myeloma IgE(DES). These antibodies were of the IgM class, based on their susceptibility to reduction, sedimentation in sucrose gradients, gel filtration and inhibition of agglutination by anti-IgM antiserum. Autoantibody levels were studied in several groups of patients by particle-counting immunoassay using latex particles to which purified monoclonal IgE(DES) was coupled. Only sera of patients suffering from parasitosis had significantly higher levels (p less than 0.0005) than those of healthy blood donors. Cord sera had very low levels, followed by an age-dependent increase during early infancy. There was no relation (p greater than 0.10) between serum IgE and IgM antibody level. On the other hand, significant relations between IgM anti-IgE(DES) levels and serum IgM (p less than 0.0005), serum IgA (p less than 0.001) and serum IgG (p less than 0.05) were observed suggesting that high levels were caused by or related to polyclonal activation of the immune system.
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PMID:Autoantibodies of the IgM class against a human myeloma protein IgE(DES). I. Occurrence. 348 28

The prevalence and specificity of naturally occurring human IgA anti-IgE autoantibodies (a-E Ab) were studied by ELISA with anti-IgA monoclonal antibodies (mAb) and a purified myeloma IgE as solid-phase protein, i.e., IgE-DES(kappa). Such detected IgA a-E Ab were common among adults, and significantly increased geometric means (GM) were found in patients with atopy (P = 0.006; n = 41; GM = 79.3 arbitrary units (AU)/ml) and filariasis (P = 0.02; n = 41; GM = 75.9 AU/ml), as compared with nonatopic controls (n = 42; GM = 48.8 AU/ml). No such difference was observed between age-matched nonatopic (n = 22; GM = 36.7 AU/ml) and atopic (n = 22; GM = 38.6 AU/ml) children. Children had significantly (P < 0.001) lower IgA a-E Ab concentrations than adults, probably as a result of age, because IgA a-E Ab concentrations and age of children were significantly correlated (n = 44; P < 0.05; r = 0.30). IgA a-E Ab concentrations were very low in cord serum (n = 32; median < 0.1 AU/ml). Sex did not influence IgA a-E Ab concentrations in any study group. The specificity of IgA a-E Ab in nine sera was studied by ELISA inhibition assay using IgE-DES myeloma as solid-phase protein and inhibitory proteins of the IgG, IgM, IgD, and IgE classes, including five different IgE myeloma proteins, as well as three enzymatic fragments of IgE-DES. The inhibitions indicated that all IgA a-E Ab tested reacted in a low-affinity reaction with determinants restricted to IgE-DES, i.e., the solid-phase protein.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Naturally occurring human IgA autoantibodies against IgE-DES myeloma protein. Prevalence and specificity. 753 80

The specificity of IgE binding to a human basophil-like cell line (KU812) was studied by flow cytometry. Four IgE myeloma proteins, representing both light-chain types, one chimeric IgE protein, and polyclonal serum IgE blocked the direct binding of FITC-labeled IgE(DES) myeloma protein to KU812 cells in a dose-dependent and nearly equimolar way. Although not as efficiently as human IgE (from five to eight times less on a molar basis), both rat and mouse IgE blocked IgE(DES)-FITC binding to KU812 cells. In sharp contrast, all four human IgG subclasses, both IgA subclasses, and IgM myeloma proteins, as well as monomeric and heat-aggregated polyclonal human IgG, were unable to block significantly IgE(DES)-FITC binding to KU812 cells (< 0.5% on a molar basis). The cytophilic epitope on IgE was heat-susceptible (56 degrees C, 2 h), lost after reduction alkylation, and resident in the papain-derived Fc epsilon-fragment, but not in the papain-derived Fab epsilon- and Fc'epsilon-fragments nor in the pepsin-derived F(ab')2 epsilon- and Fc"epsilon-fragments. Washing and displacement experiments indicated that a major part of IgE reacted with high affinity to KU812 cells. The results indicate that the binding of IgE to KU812 cells is highly specific and involves the classical high-affinity Fc epsilon RI-receptor. Although the density of receptors is low, this human cell line offers a unique model to study IgE/Fc epsilon RI interactions.
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PMID:Demonstration of specific high-affinity Fc epsilon-receptors on the human basophil-like leukemia cell line KU812 by flow cytometry. 774 Nov 91

The levels of naturally occurring IgG and IgG subclass anti-IgE autoantibodies (a-E Ab) were studied in 71 randomly collected cord sera with ELISA using solid-phase IgE-DES myeloma protein. IgG a-E Ab were present in all cord sera, and the range was 300-fold (1.8-540 arbitrary units/ML; median = 11.8). However, this activity is the sum of two major types of a-E Ab that we refer to as isotype-specific (IS) and non-isotype-specific (NIS) because they react with E-chain-specific and myeloma-restricted epitopes, respectively. These two types of a-E Ab were distinguished in IgG subclass a-E Ab inhibition ELISA for all samples using unheated IgE-PS and heated IgE-DES as inhibitors. IS and NIS a-E Ab were found among all four IgG subclasses though with different prevalences. No significant influence of gender was observed. Comparisons within each subclass indicate that NIS a-E Ab were more common than IS a-E Ab for the IgG1 (p < 0.00005), IgG2 (p = 0.07) and IgG3 (p < 0.005) subclasses while the reverse was true for IgG4 (p < 0.00005). In fact, only a minor part of the IgG1 (7%), IgG2 (13%) and IgG3 (9%) a-E Ab activity towards IgE-DES was IS while for IgG4 it was a major part (82%). Attempts to quantify IS and NIS IgG subclass a-E Ab using chimeric IgG subclass antihapten Ab suggested that the pool of IgG a-E Ab against IgE-DES was dominated by NIS a-E Ab particularly of the IgG1 subclass. The 75 percentiles for NIS IgG1, IgG2, IgG3 and IgG4 a-E Ab were 24, < 2, 2.1 and 0.27 ng/ml, respectively, whereas the corresponding figures for IS a-E Ab were 7, < 2, < 2 and 0.90 ng/ml. The findings raise questions on the definition of a-E Ab and suggest that caution should be exercised in the interpretation of any a-E Ab results that are detected with IgE myeloma proteins. The potentially more interesting IS a-E Ab may be overshadowed by the bulk of ubiquitous NIS a-E Ab and background. Consequently, discriminatory assays are necessary if the physiological implication of naturally occurring IS IgG subclass a-E Ab is to be elucidated and these considerations are not limited to studies of cord serum.
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PMID:Disproportional distribution of isotype and non-isotype-specific IgG subclass anti-IgE autoantibodies in human cord serum. 864 75

IgE mediates its effector functions through the Fc region and it has been demonstrated that structures in the Cvarepsilon3-domain are crucial for FcvarepsilonR-binding. In order to further study structures of importance for the function of IgE, such as the carbohydrates, fragments with unmodified amino acid sequence were blunt-end cloned and expressed in baculovirus-infected Sf9 cells. Two fragments of human IgE, one encompassing the entire Fc-region (rCvarepsilon2-4) and a smaller one comprising the second and third domain (rCvarepsilon2-3), were produced and characterised with respect to epitope expression, glycosylation and FcvarepsilonR-binding. N-terminal analysis showed the expected VCSRDF-sequence of the Cvarepsilon2-domain, confirming correct cleavage of the secretion signal. Immunoblotting and gel permeation chromatography demonstrated that rCvarepsilon2-4 mainly formed a dimer, whereas rCvarepsilon2-3 also existed as monomers and oligomers. Endoglycosidase-treatment revealed that both fragments were N-glycosylated. In inhibition ELISA, rCvarepsilon2-4 and myeloma protein IgE(DES) reacted in a near equimolar way with monoclonal antibodies against the Cvarepsilon2-, Cvarepsilon3- and Cvarepsilon4-domains, whereas rCvarepsilon2-3 only reacted with anti-Cvarepsilon2 mAbs. Moreover, in FACS analysis rCvarepsilon2-4 interacted with two cell-lines constitutively expressing FcvarepsilonRI or FcvarepsilonRII, whereas rCvarepsilon2-3 lacked reactivity. A substantial reduction in the ability of rCvarepsilon2-4, following endoglycosidase treatment, to react with recombinant alpha-chain of the high affinity receptor for IgE in sandwich ELISA, indicated a role of N-linked oligosaccharides in stabilising receptor binding structures. Taken together, our results show that rCvarepsilon2-4, but not rCvarepsilon2-3, will be useful in studies of structure-function relationships of IgE, including the role of N-glycosylation, since it demonstrated appropriate epitope expression, conformation and ability to bind Fcvarepsilon-receptors.
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PMID:Characterisation of recombinant human IgE-Fc fragments expressed in baculovirus-infected insect cells. 1086 16