Autoantibodies to β
            <sub>2</sub>
            -Adrenergic Receptors: a Possible Cause of Adrenergic Hyporesponsiveness in Allergic Rhinitis and Asthma

Jc, Venter; Cm, Fraser; Harrison, Len C.

doi:10.1126/science.6153472

Cited by 190 publications

(53 citation statements)

References 18 publications

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“…1 mg of free peptide was emulsified in com- Immunoblotting assay. Rat cardiac membrane was used as the source of muscarinic receptor-2 for immunoblotting and radioligand binding since heterologous systems have been previously used to demonstrate antireceptor antibodies in human disease (7,(12)(13)(14). Moreover, the peptide we used corresponds to a sequence totally conserved in both humans and rats ( 15).…”

Section: Methodsmentioning

confidence: 99%

Localization of a functional autoimmune epitope on the muscarinic acetylcholine receptor-2 in patients with idiopathic dilated cardiomyopathy.

Fu¹,

Magnusson²,

Bergh³

et al. 1993

J. Clin. Invest.

264

149

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A peptide corresponding to the sequence 169-193 of the second extracellular loop of the human muscarinic acetylcholine receptor-2 was used as an antigen to screen sera from patients with idiopathic dilated cardiomyopathy (DCM, n = 36) and healthy blood donors (HBD, n = 40). The sera from 14 patients with DCM (38.8%) and 3 HBD (7.5%) recognized the muscarinic receptor peptide at dilutions varying from 1:20 to 1:160 in ELISA. A highly significant correlation (P = 0.006) was found between the presence of antimuscarinic receptor-2 autoantibodies and anti-fl-adrenoceptor-1 autoantibodies in the patients' sera. Affinity-purified autoantibodies from positive sera of patients with DCM recognized on the electrotransferred protein of rat ventricular membrane a major band of about 80 kD. Incubation of autoantibodies with membrane resulted not only in a decrease in the maximal binding sites (B..) but also in an increase in Kd of radioligand binding in a concentration-dependent manner. This suggests a mixed-type of inhibition. Moreover, preincubation with atropine abolished the inhibitory effect of autoantibodies on the receptor binding whereas carbachol appeared to have no effect on the activity of the autoantibodies.These data define a subgroup of patients with idiopathic DCM who have in their sera functionally active autoantibodies against muscarinic receptor-2. (J. Clin. Invest. 1993Invest. .91:1964Invest. -1968

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Section: Methodsmentioning

confidence: 99%

Localization of a functional autoimmune epitope on the muscarinic acetylcholine receptor-2 in patients with idiopathic dilated cardiomyopathy.

Fu¹,

Magnusson²,

Bergh³

et al. 1993

J. Clin. Invest.

264

149

View full text Add to dashboard Cite

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“…Recently, autoantibodies for cell surface molecules have been detected in patients with myasthenia gravis, Graves disease, insulin-resistant diabetes, or asthma (3)(4)(5)(6). These antibodies are assumed to be closely related to the pathogenesis of the symptoms that these diseases produce.…”

mentioning

confidence: 99%

Presence of autoantibody for phospholipase inhibitory protein, lipomodulin, in patients with rheumatic diseases.

Hirata¹,

Carmine²,

Nelson³

et al. 1981

Proc. Natl. Acad. Sci. U.S.A.

134

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The activity of phospholipase inhibitory protein, lipomodulin, partially purified from rabbit neutrophils, was markedly decreased after treatment with sera from patients with rheumatic diseases such as systemic lupus erythematosus, rheumatoid arthritis, and dermatomyositis. The decrease of the protein's inhibitory activity on phospholipase A2 paralleled the amount of [35S]methionine-labeled lipomodulin precipitated by the sera. Absorption ofpatients' sera with anti-human IgM (,u chain) or protein A-agarose, but not with anti-human IgG (ychain), decreased their ability to decrease. the activity of lipomodulin on phospholipase A2 or to precipitate the radioactive li omodulin. The IgM fraction of patients' sera could precipitate [ S]methionine-labeled lipomodulin (40,000 daltons) which comigrated with highly purified Iipomodulin on gel electrophoresis with sodium dodecyl sulfate. All of these observations suggest that the sera of many patients with rheumatic diseases contain autoantibody against lipomodulin. A monoclonal antibody against lipomodulin was also obtained. Stimulating human fibroblasts with bradykinin in the presence of monoclonal antilipomodulin antibody markedly enhanced arachidonic acid release due to the activation of phospholipase(s) in the intact cells, and this stimulatory effect was blocked by adding purified lipomodulin. These findings suggest that lipomodulin regulates the activity of phospholipase(s) on the cell surface and that autoantibodies against lipomodulin may play a role in certain symptoms of rheumatic diseases, especially by the formation of prostaglandins and other metabolites of arachidonic acid.A phospholipase A2 inhibitory protein, which we propose to name "lipomodulin," was recently isolated from neutrophils treated with glucocorticoids (1). This protein was found to inhibit phospholipase A2 (phosphatide 2-acylhydrolase, EC 3.1.1.4), an enzyme that cleaves the ester bond in the A3-position of phosphatidylcholine, to liberate unsaturated fatty acids (mainly arachidonic acid) and lysophosphatidylcholine. Lipomodulin was shown to be induced by glucocorticoids in a receptor-mediated fashion (1). The inhibitory action of glucocorticoids on prostaglandin formation has been assumed to be due to induction of this inhibitory protein, which decreases the availability of the precursor ofprostaglandins, arachidonic acid, by inhibiting phospholipase A2 (1, 2).Recently, autoantibodies for cell surface molecules have been detected in patients with myasthenia gravis, Graves disease, insulin-resistant diabetes, or asthma (3-6). These antibodies are assumed to be closely related to the pathogenesis of the symptoms that these diseases produce. Because prostaglandins and hydroxyl compounds of arachidonic acid are thought to play a role in the pathophysiology of rheumatic diseases (7), we initiated a search for autoantibodies against lipomodulin.We report here the presence of autoantibodies against lipomodulin, a cell surface protein, in the sera of many patients with rheumatic diseases su...

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“…Autoantibodies to insulin receptors, which have been identified in certain insulin-resistant diabetics, have been valuable tools in elucidating the subunit structure of the insulin receptor (1,2). The solubilization and characterization of mammalian f3-adrenergic receptors (3) permitted the detection of auto-antibodies to (32-adrenergic receptors in serums of patients with asthma or allergic respiratory disease (4,5). These autoantibodies which interact with lung /2 receptors but not cardiac f3i receptors (4) have been utilized in this laboratory to purify calf lung /-adrenergic receptors (6).…”

mentioning

confidence: 99%

“…The solubilization and characterization of mammalian f3-adrenergic receptors (3) permitted the detection of auto-antibodies to (32-adrenergic receptors in serums of patients with asthma or allergic respiratory disease (4,5). These autoantibodies which interact with lung /2 receptors but not cardiac f3i receptors (4) have been utilized in this laboratory to purify calf lung /-adrenergic receptors (6). However, the impurity and low titers of human /-receptor autoantibodies (4) as well as the probable polyclonal nature of the autoantibodies may limit their utility.…”

mentioning

confidence: 99%

Monoclonal antibodies to beta-adrenergic receptors: use in purification and molecular characterization of beta receptors.

Fraser¹,

Venter²

1980

Proc. Natl. Acad. Sci. U.S.A.

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We have developed four hybridomas that produce monoclonal antibodies to the turkey erythrocyte nj-adrenergic receptor and one hybridoma that produces a monoclonal antibody to the calf lung & receptor. Splenic lymphocytes from BALB/c mice immunized with partially purified turkey erythrocyte #I receptors or calf lung ,2 receptors were fused with the mouse myeloma line SP2/0Agl4 to yield hybridoma cultures producing , receptor monoclonal antibies of the IgG class.

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Autoantibodies to β ₂ -Adrenergic Receptors: a Possible Cause of Adrenergic Hyporesponsiveness in Allergic Rhinitis and Asthma

Cited by 190 publications

References 18 publications

Localization of a functional autoimmune epitope on the muscarinic acetylcholine receptor-2 in patients with idiopathic dilated cardiomyopathy.

Localization of a functional autoimmune epitope on the muscarinic acetylcholine receptor-2 in patients with idiopathic dilated cardiomyopathy.

Presence of autoantibody for phospholipase inhibitory protein, lipomodulin, in patients with rheumatic diseases.

Monoclonal antibodies to beta-adrenergic receptors: use in purification and molecular characterization of beta receptors.

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Autoantibodies to β 2 -Adrenergic Receptors: a Possible Cause of Adrenergic Hyporesponsiveness in Allergic Rhinitis and Asthma

Cited by 190 publications

References 18 publications

Localization of a functional autoimmune epitope on the muscarinic acetylcholine receptor-2 in patients with idiopathic dilated cardiomyopathy.

Localization of a functional autoimmune epitope on the muscarinic acetylcholine receptor-2 in patients with idiopathic dilated cardiomyopathy.

Presence of autoantibody for phospholipase inhibitory protein, lipomodulin, in patients with rheumatic diseases.

Monoclonal antibodies to beta-adrenergic receptors: use in purification and molecular characterization of beta receptors.

Contact Info

Product

Resources

About

Autoantibodies to β ₂ -Adrenergic Receptors: a Possible Cause of Adrenergic Hyporesponsiveness in Allergic Rhinitis and Asthma