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.
Wallenberg Laboratory, Sahlgren's Hospital, University of Göteborg, Sweden.
M L
ML
Fu
H
H
Herlitz
W
W
Schulze
G
G
Wallukat
P
P
Micke
P
P
Eftekhari
K G
KG
Sjögren
A
A
Hjalmarson
W
W
Müller-Esterl
J
J
Hoebeke
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