of the Max - MDC

number of circulating antibodies to the beta1-adrenoceptor
and the improvement of heart function supports the
hypothesis that the anti-beta1-adrenoceptor autoantibodies
may play a role in the development of myocarditis, DCM,
and PPCM.
Antibodies against the beta2-adrenoceptor
Recently, we identified agonistic antibodies against this
adrenoceptor subtype in the sera of glaucoma patient’s.
Glaucoma is a frequent ocular disease leading to blindness.
Primary open-angle glaucoma and ocular hypertension are
the common forms of glaucomolus diseases. The disorders
are driven by high intraocular pressure. Moreover, the
chamber water production is regulated via a beta2-adrenergic
signal cascade. The pathogenesis of glaucoma is widely
unknown. We observed the antibodies against the beta2-
adrenoceptor in 75% of the glaucoma serum samples investigated.
The antibodies which are immunoglobulins of the
IgG3 subclass recognized an epitope in the middle part of
the second extracellular loop. These agonist-like antibodies
prevent the desensitization of the beta2-adrenoceptor
mediated signal cascade.
More recently, we observed agonistic antibodies against the
beta2-adrenoceptor in patients with Alzheimer’s disease.
The antibodies were detectable in 70% of the patient sera,
investigated. They were observed together with an antibody
directed against the alpha1 adrenoceptor. The beta2-
adrenoceptor antibodies which are antibodies of the IgG3
subclass recognized an epitope on the first extracellular
loop of the beta2 adrenoceptor.
Moreover, we observed agonistic antibodies against the
beta2-adrenoceptor in patients with Chagas’ disease in particular
in patients which develop a megacolon. These antibodies
recognize an epitope near the N-terminus of the second
extracellular loop and are also immunoglobulins of the
IgG3 subclass.
Antibodies against the endothelin1 ETA receptor
and the protease activated receptors PAR1 and
PAR2
Antibodies against the endothelin1 ETA receptor were firstly
identified by our group in patients with Raynaud’s syndrome
and scleroderma. In our test system these antibodies (like
endothelin 1) induce a negative chronotropic effect that
was blocked by the antagonists of the ETA receptor BQ610.
The antagonist of the ETB receptor BQ 788 was without
influence. Moreover, the effect of the agonist-like antibodies
against the ETA receptor was neutralized by peptides
corresponding to the second extracellular loop of the ETA
receptor.
We identified the epitope on the second extracellular loop
and the IgG subclass (IgG2 subclass). The antibodies purified
by affinity chromatography activated the transcription
factors AP-1 and NFκB.
In patients with Raynaud’s syndrome and scleroderma we
observed a second agonist-like antibody. This antibody recognized
the protease activated receptors PAR1 (thrombin
receptor) and PAR2 (tryptase receptor). These antibodies
exerted a positive chronotropic effect and were blocked by
an inhibitory peptide of the thrombin receptor and neutralized
by peptides corresponding to the second extracellular
loop.
Antibodies against the ETA receptor were also observed in
patients with pulmonary hypertension. Pulmonary hypertension
is a progressive fatal disease of unknown cause. This
disease is accompanied by an increase of tonus and a
Cardiovascular and Metabolic Disease Research 49