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)

IgE antibodies are usually thought to induce only immediate skin reactions. We have shown that the intradermal injection of a number of different allergens can produce a prolonged inflammatory reaction after the immediate wheal and flare in most sensitive subjects. This late inflammatory response occurs 6-12 h after challenge and is characterized by diffuse edema, erythema, pruritus, and heat. Both immediate and late responses can also be seen after passive sensitization of skin sites in nonatopic subjects. That IgE is involved in inducing the reaction was shown by the abolition of both immediate and late responses by passive transfer tests in the following experiments: (a) heating atopic serum at 56degreesC for 4 h, (b) removing IgE from the atopic serum by a solid phase anti-IgE immunoabsorbent, and (c) competitively inhibiting the binding of IgE antibodies to cells by an IgE myeloma protein. In addition, both responses were induced by affinity chromatography-purified IgE antibody, followed by antigenic challenge. Very similar lesions could also be induced by intradermal injection of Compound 48/80, thus suggesting a central role in the reaction for the mast cell or basophil. Histologically, the late phase is characterized by edema and a mixed cellular infiltration, predominantly lymphocytic but also containing eosinophils, neutrophils and basophils. Direct immunofluorescent staining did not show deposition of immunoglobulins or complement components, except IgM in 2 of 15 and C3 in 1 of 15 patients. This finding indicates that the late phase does not depend on the deposition of immune complexes. The results of the study suggest that IgE-allergen interaction on the surfaces of mast cells or on infiltrating basophils causes both immediate and late cutaneous responses.
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PMID:The late phase of the immediate wheal and flare skin reaction. Its dependence upon IgE antibodies. 78 99

Peptostreptococcus magnus strain 312 (10(6) to 10(8)/ml), which synthesizes a protein capable of binding to kappa L chains of human Ig (protein L), stimulated the release of histamine from human basophils in vitro. P. magnus strain 644, which does not synthesize protein L, did not induce histamine secretion. Soluble protein L (3 x 10(-2) to 3 micrograms/ml) induced histamine release from human basophils. The characteristics of the release reaction were similar to those of rabbit IgG anti-Fc fragment of human IgE (anti-IgE): it was Ca2(+)- and temperature-dependent, optimal release occurring at 37 degrees C in the presence of 1.0 mM extracellular Ca2+. There was an excellent correlation (r = 0.82; p less than 0.001) between the maximal percent histamine release induced by protein L and that induced by anti-IgE, as well as between protein L and protein A from Staphylococcus aureus (r = 0.52; p less than 0.01). Preincubation of basophils with either protein L or anti-IgE resulted in complete cross-desensitization to a subsequent challenge with the heterologous stimulus. IgE purified from myeloma patients PS and PP (lambda-chains) blocked anti-IgE-induced histamine release but failed to block the histamine releasing activity of protein L. In contrast, IgE purified from myeloma patient ADZ (kappa-chains) blocked both anti-IgE- and protein L-induced releases, whereas human polyclonal IgG selectively blocked protein L-induced secretion. Protein L acted as a complete secretagogue, i.e., it activated basophils to release sulfidopeptide leukotriene C4 as well as histamine. Protein L (10(-1) to 3 micrograms/ml) also induced the release of preformed (histamine) and de novo synthesized mediators (leukotriene C4 and/or PGD2) from mast cells isolated from lung parenchyma and skin tissues. Intradermal injections of protein L (0.01 to 10 micrograms/ml) in nonallergic subjects caused a dose-dependent wheal-and-flare reaction. Protein L activates human basophils and mast cells in vitro and in vivo presumably by interacting with kappa L chains of the IgE isotype.
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PMID:Protein L. A bacterial Ig-binding protein that activates human basophils and mast cells. 169 70

Circulating histamine releasing factor(s) have been demonstrated previously in chronic urticaria by an immediate weal-and-flare response to intradermal autologous serum injection. We have studied 25 chronic urticaria patients by in vivo skin testing with autologous sera and an in vitro histamine release assay using mixed leukocytes of healthy donors, to define the nature and functional properties of the serum factor(s). Twenty showed a weal response to autologous serum (mean +/- s.e.m., 37.3 +/- 6.8 mm3). Weal formation was confined to ultrafiltered serum fractions greater than 100 kD in nine of nine patients. There was no response in 10 healthy controls of five patients with symptomatic dermographism. Fourteen chronic urticaria sera elicited histamine release greater than 10% (mean +/- s.e.m., 44.3% +/- 6.7) above basal levels from leukocytes of at least one of seven healthy donors. This in vitro response was also confined to ultrafiltered serum fractions greater than 100 kD in seven of seven sera and was present in IgG fractions of six of seven chronic urticaria sera that showed histamine releasing activity. Functional studies indicated that this histamine releasing autoantibody had the properties of anti-IgE: chronic urticaria sera 'desensitized' basophil leukocytes to subsequent challenge with other chronic urticaria sera and to goat anti-human IgE antibody; human myeloma IgE inhibited histamine release from leukocytes in response to chronic urticaria sera; removal of surface-bound IgE by lactic acid 'stripping' reduced histamine release in response to chronic urticaria sera and anti-IgE and subsequent passive sensitization with IgE myeloma serum partially restored it. Stainable peripheral blood basophils/mm3 in chronic urticaria patients were significantly reduced (mean +/- s.e.m, 7.9 +/- 2.0) when compared to healthy controls (39.6 +/- 4.4), P less than 0.001. These results suggest that histamine releasing autoantibodies are important in the pathogenesis of chronic urticaria by stimulating or facilitating degranulation of basophils and cutaneous mast cells through cross-linking cell surface IgE receptors.
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PMID:Detection of circulating histamine releasing autoantibodies with functional properties of anti-IgE in chronic urticaria. 172 43

The prevalence of autoantibodies of immunoglobulin G (IgG) and immunoglobulin M (IgM) classes directed against myeloma immunoglobulin E (IgE) were determined in distinct subsets of urticaria, using an enzyme immunoassay. IgG anti-IgE antibodies were found in five of nine patients (55%) with cold urticaria, four of eight patients (50%) with urticarial vasculitis, and three of six patients (50%) with chronic urticaria. IgM anti-IgE antibodies were found exclusively in cold urticaria (two of nine patients, 22%). Heating of these sera increased the binding to IgE, suggesting immune complex formation. Several positive sera were capable of inducing histamine release from normal peripheral basophils and caused a wheal-flare response upon intradermal injection. Sera containing such autoantibodies from three cold urticaria patients were studied for passive transfer of cold sensitivity. One serum containing IgG anti-IgE gave a strongly positive transfer test at 5 h but not 48 h, suggesting a pathogenic role for the IgG.
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PMID:Prevalence and functional role of anti-IgE autoantibodies in urticarial syndromes. 244 92

Generalized urticaria and fever were noted in a patient with IgA (kappa) myeloma after intravenous cyclophosphamide. Intradermal skin testing revealed no reaction to cyclophosphamide and its analog, isophosphamide. However, phosphoramide mustard, a principle metabolite of cyclophosphamide, evoked an immediate wheal-and-flare response. Subsequent therapy with isophosphamide was well tolerated. These findings suggest that acute hypersensitivity reactions to cyclophosphamide are due to its metabolites and can be delineated with skin testing.
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PMID:Hypersensitivity reaction to a metabolite of cyclophosphamide. 405 47

We report a case of atypical urticaria associated with IgA multiple myeloma. A 79-year-old man presented with a two-month history of wheal-like erythema, which lasted approximately one week without any response to anti-histamines. Histological examination of a lesion revealed leukocytoclasia as well as perivascular leukocytic infiltration, being consistent with urticarial erythema. Laboratory investigation showed markedly elevated serum IgA concentration and M-protein in serum protein electrophoresis. A bone marrow examination led to a diagnosis of myeloma. An immunofluorescence study failed to detect any IgA deposit in the lesion. However, the wheal-like eruptions disappeared when the IgA myeloma was treated and reappeared when it relapsed. We conclude that this long lasting urticaria was the cutaneous manifestation of IgA myeloma.
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PMID:Urticarial erythema associated with IgA myeloma. 1549 40