Helmholtz Gemeinschaft


Agonistic autoantibodies to the β2-adrenergic receptor involved in the pathogenesis of open-angle glaucoma

[thumbnail of 17132.pdf]
PDF - Requires a PDF viewer such as GSview, Xpdf or Adobe Acrobat Reader

Item Type:Article
Title:Agonistic autoantibodies to the β2-adrenergic receptor involved in the pathogenesis of open-angle glaucoma
Creators Name:Jünemann, A., Hohberger, B., Rech, J., Sheriff, A., Fu, Q., Schlötzer-Schrehardt, U., Voll, R.E., Bartel, S., Kalbacher, H., Hoebeke, J., Rejdak, R., Horn, F., Wallukat, G., Kunze, R. and Herrmann, M.
Abstract:Glaucoma is a frequent ocular disease that may lead to blindness. Primary open-angle glaucoma (POAG) and ocular hypertension (OHT) are common diseases with increased intraocular pressure (IOP), which are mainly responsible for these disorders. Their pathogenesis is widely unknown. We screened the sera of patients with POAG and OHT for the prevalence of autoantibodies (AAb) against G protein-coupled receptors (GPCRs) in comparison to controls. Employing frequency modulation of spontaneously contracting neonatal rat cardiomyocytes, agonistic GPCR AAb were to be detected in roughly 75% of the patients with POAG and OHT, however, not in controls. Using inhibitory peptides the AAb' target was identified as β2 adrenergic receptor (β2AR). The AAb interact with the second extracellular loop of β2AR. The peptides 181-187 and 186-192 were identified as binding sites of the AAb within the extracellular loop II. The binding of the AAb to β2ARs was verified by surface-plasmon-resonance analysis. The isotype of the AAb was (immunoglobulin) IgG3. In an additional pilot principal-of-proof study, including four patients with POAG, the removal of the AAb against the β2AR and other immunoglobulins G by immunoadsorption resulted in a transient reduction of IOP. These findings might indicate a possible role of agonistic AAb directed against β2ARs in the dynamics of aqueous humor and might support a contribution of adaptive autoimmunity in the etiopathogenesis of POAG and OHT.
Keywords:Autoantibodies, Glaucoma, Ocular Hypertension, β2-Adrenergic Receptor, Agonistic, Immunoadsorption, Animals, Rats, Sprague-Dawley
Source:Frontiers in Immunology
Publisher:Frontiers Media SA
Page Range:145
Date:12 February 2018
Official Publication:https://doi.org/10.3389/fimmu.2018.00145
PubMed:View item in PubMed

Repository Staff Only: item control page


Downloads per month over past year

Open Access
MDC Library