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Functional autoimmune epitope on alpha 1-adrenergic receptors in patients with malignant hypertension.

Artikel i vetenskaplig tidskrift
Författare Michael Fu
Hans Herlitz
G Wallukat
E Hilme
Thomas Hedner
Johan Hoebeke
Åke Hjalmarson
Publicerad i Lancet
Volym 344
Nummer/häfte 8938
Sidor 1660-3
ISSN 0140-6736
Publiceringsår 1994
Publicerad vid Wallenberglaboratoriet
Institutionen för invärtesmedicin
Sidor 1660-3
Språk en
Länkar www.ncbi.nlm.nih.gov/entrez/query.f...
Ämnesord Adult, Animals, Autoantibodies, blood, immunology, Enzyme-Linked Immunosorbent Assay, Epitopes, immunology, Female, Humans, Hypertension, immunology, Hypertension, Malignant, immunology, Male, Middle Aged, Prazosin, immunology, Rats, Rats, Wistar, Receptors, Adrenergic, alpha, immunology, Receptors, Muscarinic, immunology
Ämneskategorier Fysiologi, Mikrobiologi inom det medicinska området

Sammanfattning

Because of the growing evidence that hypertensive disease is accompanied by immunological dysfunction, we have investigated autoimmunity in patients with malignant hypertension. Peptides corresponding to the sequence of the second extracellular loops of the human alpha 1-adrenergic receptor and the M2-muscarinic receptor were used as antigens in an ELISA. Serum from 4 (12%) of 33 healthy controls, 3 (20%) of 15 patients with malignant essential hypertension, and 7 (64%) of 11 with secondary hypertension showed positive responses in the ELISA for the alpha 1-adrenergic receptor peptide. Positive responses were significantly more common among the patients with secondary hypertension than in the other two groups (p < 0.01). By contrast, no autoantibodies against the M2-muscarinic receptor peptide were detected in either hypertensive group. Autoantibodies against the alpha 1-adrenergic receptor, affinity-purified from patients with positive responses, specifically recognised bands with molecular masses of 68, 40, and 37 kDa on immunoblotted membrane proteins of rat ventricles. The patients' autoantibodies caused a decrease in tritiated prazosin binding sites and an increase in heart beating frequency of neonatal cultured rat cardiomyocytes; antibodies purified from the controls had no effect. Circulating autoantibodies against the alpha 1-adrenergic receptor are present in a subgroup of patients with malignant hypertension. These autoantibodies have pharmacological activity in vitro, which suggests that they may be involved in the pathogenesis of malignant hypertension.

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