Autoantibodies Activating the β2-Adrenergic Receptor Characterize Patients With Primary and Secondary Glaucoma

Bettina Hohberger, Rudolf Kunze, Gerd Wallukat, Katja Kara, Christian Y Mardin, Robert Lämmer, Ursula Schlötzer-Schrehardt, Sami Hosari, Folkert Horn, Luis Munoz, Martin Herrmann, Bettina Hohberger, Rudolf Kunze, Gerd Wallukat, Katja Kara, Christian Y Mardin, Robert Lämmer, Ursula Schlötzer-Schrehardt, Sami Hosari, Folkert Horn, Luis Munoz, Martin Herrmann

Abstract

Recently, agonistic autoantibodies (agAAb) activating the β2-adrenergic receptor were detected in primary open-angle glaucoma (POAG) or ocular hypertension (OHT) patients and were linked to intraocular pressure (IOP) (1). The aim of the present study was to quantify β2-agAAb in the sera of glaucoma suspects and patients with primary and secondary glaucoma. Patients with OHT (n = 33), pre-perimetric POAG (pre-POAG; n = 11), POAG (n = 28), and 11 secondary OAG (SOAG) underwent ophthalmological examinations including examinations with Octopus G1 perimetry and morphometry. Twenty-five healthy individuals served as controls. Serum-derived IgG samples were analyzed for β2-agAAb using a functional bioassay. The beat-rate-increase of spontaneously beating cultured neonatal rat cardiomyocytes was monitored with 1.6 beats/15 s as cut-off. None of the sera of normal subjects showed β2-agAAb. In POAG or OHT patients increased beating rates of 4.1 ± 2.2 beats/15 s, and 3.7 ± 2.8 beats/15 s were detected (p > 0.05). Glaucoma patients with (POAG) and without perimetric (pre-POAG) defects did not differ (pre-POAG 4.4 ± 2.6 beats/15 s, POAG 4.1 ± 2.0 beats/15 s, p > 0.05). Patients with SOAG yielded mean beating rates of 4.7 ± 1.7 beats/15 s (p > 0.05). β2-agAAb were seen in 73% of OHT, 82% of pre-POAG, 82% of POAG, and 91% SOAG patients (p < 0.001). Clinical data did not correlate with beating rate (p > 0.05). The robust β2-agAAb seropositivity in patients with OHT, pre-POAG, POAG, and SOAG suggest a primary common role for β2-agAAb starting early in glaucoma pathophysiology and turned out to be a novel marker identifying all patients with increased IOP independent of glaucoma stage and entity.

Trial registration: ClinicalTrials.gov NCT00494923.

Keywords: autoantibodies; glaucoma; ocular hypertension; primary open-angle glaucoma; secondary open-angle glaucoma; β2-adrenergic receptor.

Copyright © 2019 Hohberger, Kunze, Wallukat, Kara, Mardin, Lämmer, Schlötzer-Schrehardt, Hosari, Horn, Munoz and Herrmann.

Figures

Figure 1
Figure 1
β2-agAAb in patients with OHT, primary, and secondary glaucoma. Cardiomyocyte beating rates [beats/15 s] modulated by IgG from sera of control subjects (normal healthy donor, NHD), patients with ocular hypertension (OHT), pre-perimetric POAG (primary open-angle glaucoma), POAG, and SOAG (secondary open-angle glaucoma) (cut-off 1.6 beats/15 s); cardiomyocyte beating rate is counted as difference of the baseline value (i.e., spontaneously beating rate of cultured cardiomyocytes) and the activated beating rate after addition of the test samples; therefore, some negative values were recorded.

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