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

Beitrag in einer Fachzeitschrift


Details zur Publikation

Autor(en): Juenemann A, Hohberger B, Rech J, Sheriff A, Fu Q, Schlötzer-Schrehardt U, Voll RE, Bartel S, Kalbacher H, Hoebeke J, Rejdak R, Horn F, Wallukat G, Kunze R, Herrmann M
Zeitschrift: Frontiers in Immunology
Jahr der Veröffentlichung: 2018
Band: 9
ISSN: 1664-3224


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 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.


FAU-Autoren / FAU-Herausgeber

Herrmann, Martin Prof. Dr.
Medizinische Klinik 3 - Rheumatologie und Immunologie
Horn, Folkert Dr. rer. biol. hum.
Augenklinik
Medizinische Klinik 3 - Rheumatologie und Immunologie
Schlötzer-Schrehardt, Ursula apl. Prof. Dr.
Medizinische Fakultät


Autor(en) der externen Einrichtung(en)
Eberhard Karls Universität Tübingen
Huazhong University of Science & Technology
Max-Delbrück-Centrum für Molekulare Medizin (MDC) Berlin-Buch
Medical University of Lublin / Uniwersytet Medyczny w Lublinie
National Center for Scientific Research / Centre national de la recherche scientifique (CNRS)
Universität Rostock


Zitierweisen

APA:
Juenemann, A., Hohberger, B., Rech, J., Sheriff, A., Fu, Q., Schlötzer-Schrehardt, U.,... Herrmann, M. (2018). Agonistic Autoantibodies to the β2-Adrenergic Receptor Involved in the Pathogenesis of Open-Angle Glaucoma. Frontiers in Immunology, 9. https://dx.doi.org/10.3389/fimmu.2018.00145

MLA:
Juenemann, Anselm, et al. "Agonistic Autoantibodies to the β2-Adrenergic Receptor Involved in the Pathogenesis of Open-Angle Glaucoma." Frontiers in Immunology 9 (2018).

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Zuletzt aktualisiert 2019-17-04 um 08:17