Autoantibodies against the angiotensin receptor (AT1) in patients with hypertension.
Sera from patients with malignant essential hypertension (n = 14), malignant secondary hypertension mainly attributable to renovascular diseases (n = 12) and renovascular diseases without malignant hypertension (n = 11) and from normotensive healthy blood donors (n = 35) were studied for the presence of autoantibodies against G-protein-coupled cardiovascular receptors. Autoantibodies against the angiotensin II receptor (AT1) were detected in 14, 33, 18 and 14% of patients with malignant essential hypertension, malignant secondary hypertension, renovascular diseases and control patients, respectively. Sensitivity of the enzyme immunoassay was assessed as 5 microg/ml IgG. Patients did not show antibodies against bradykinin (B2) or angiotensin II subtype 2 (AT2) receptors. Autoantibodies affinity-purified from positive patients localized AT receptors in Chinese hamster ovary transfected cells, and displayed a positive chronotropic effect on cultured neonatal rat cardiomyocytes. These results demonstrate the existence of autoantibodies against a functional extracellular domain of human AT1 receptors in patients with malignant hypertension, and suggest that these autoantibodies might be involved in the pathogenesis of malignant hypertension.
Fu
M L
ML
Wallenberg Laboratory, Sahlgren's Hospital, University of Göteborg, Sweden.
Herlitz
H
H
Schulze
W
W
Wallukat
G
G
Micke
P
P
Eftekhari
P
P
Sjögren
K G
KG
Hjalmarson
A
A
Müller-Esterl
W
W
Hoebeke
J
J
D000818:Animals; D001323:Autoantibodies / Q000276:immunology*; D015415:Biomarkers / Q000097:blood; D002478:Cells, Cultured; D006224:Cricetinae; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006352:Heart Ventricles / Q000196:embryology / Q000276:immunology / Q000378:metabolism; D006801:Humans; D006974:Hypertension, Malignant / Q000097:blood / Q000276:immunology*; D006977:Hypertension, Renal / Q000097:blood / Q000276:immunology*; D007074:Immunoglobulin G / Q000276:immunology*; D007672:Kidney Cortex / Q000166:cytology / Q000276:immunology / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D010053:Ovary / Q000166:cytology / Q000276:immunology / Q000378:metabolism; D051381:Rats; D044140:Receptor, Angiotensin, Type 1; D011945:Receptors, Angiotensin / Q000097:blood / Q000276:immunology*
D001323:Autoantibodies; D015415:Biomarkers; D007074:Immunoglobulin G; D044140:Receptor, Angiotensin, Type 1; D011945:Receptors, Angiotensin