Agonistic Autoantibodies to the β2-Adrenergic Receptor Involved in the Pathogenesis of Open-Angle Glaucoma

Frontiers in Immunology

Rudolf Kunze¹  Johan Hoebeke²  Robert Rejdak³  Martin Herrmann⁴  Ahmed Sheriff⁴  Jürgen Rech⁴  Folkert Horn⁵  Bettina Hohberger⁵  Ursula Schlötzer-Schrehardt⁵  Anselm Jünemann⁶  Hubert Kalbacher⁸  Reinhard Edmund Voll⁹  Qin Fu^1,10  Sabine Bartel^1,10  Gerd Wallukat^1,10 

[1] 0Science Office, Berlin-Buch, Campus Max Delbrück Center for Molecular Medicine, Berlin, Germany;C.N.R.S. UPR 9021 «Chimie et Immunologie Thérapeutiques», Strasbourg, France;Department of General Ophthalmology, Medical University of Lublin, Lublin, Poland;Department of Internal Medicine III, Institute of Clinical Immunology and Rheumatology, University of Erlangen-Nürnberg, Erlangen, Germany;Department of Ophthalmology, Friedrich-Alexander-University of Erlangen-Nürnberg, Erlangen, Germany;Department of Ophthalmology, University of Rostock, Rostock, Germany;Department of Pharmacology, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China;IFIB - Institute of Biochemistry, University of Tübingen, Tübingen, Germany;IZKF Research Group 2, Nikolaus-Fiebiger-Center of Molecular Medicine, University of Erlangen-Nürnberg, Erlangen, Germany;Max Delbrück Center for Molecular Medicine, Berlin, Germany;

关键词: autoantibodies;    glaucoma;    ocular hypertension;    β2-adrenergic receptor;    agonistic;    immunoadsorption;   

DOI  :  10.3389/fimmu.2018.00145

来源: DOAJ

【 摘 要 】

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 in vitro, 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.

【 授权许可】

Unknown