Agonistic β2-Adrenergic Receptor Autoantibodies Characterize the Aqueous Humor of Patients With Primary and Secondary Open-Angle Glaucoma.

Bettina Hohberger,Gerd Wallukat,Rudolph Kunze,Max Wörn,Robert Lämmer,Christian Mardin,Ursula Schötzer-Schrehardt,Aparna Mahajan,Martin Herrmann

doi:10.3389/fimmu.2021.550236

Abstract

PurposeAgonistic β2-adrenergic receptor autoantibodies (β2-agAAbs) were recently observed in sera of patients with ocular hypertension (OHT), primary (POAG), and secondary open-angle glaucoma (SOAG), yet not in healthy controls (HCs). It was the aim of the present study to investigate the presence of β2-agAAb in aqueous humor (AH) samples of OAG patients and to correlate these with the corresponding β2-agAAb serum data.Material and MethodsThirty-nine patients (21 male, 18 female) were recruited from the Department of Ophthalmology, University of Erlangen-Nürnberg: twenty-one POAG, 18 SOAG. Aqueous humor samples were collected during minimal invasive glaucoma surgery. Serum and AH samples were analyzed for β2-agAAb by a bioassay quantifying the beating rate of cultured cardiomyocyte (cut-off: 2 U).ResultsThirty-six of 39 (92.3%) and 34 of 39 (87.2%) of OAG patients showed a β2-agAAb in their sera and AH samples, respectively. All β2-agAAb AH-positive OAG patients were also seropositive. We also observed a β2-agAAb seropositivity in 95 and 89% of patients with POAG and SOAG, respectively. Beta2-agAAbs were seen in 86% (POAG) and 78% (SOAG) of AH samples. The β2-agAAb adrenergic activity was increased in the AH of patients with POAG (6.5 ± 1.5 U) when compared with those with SOAG (4.1 ± 1.1 U; p = 0.004). Serum β2-agAAb adrenergic activity did not differ between the cohorts [POAG (4.5 ± 1.5 U); SOAG (4.6 ± 2.1 U; p=0.458)]. No correlation of the beating rates were observed between serum and AH samples for group and subgroup analyses.ConclusionThe detection of β2-agAAb in systemic and local circulations supports the hypothesis of a direct functional impact of these agAAbs on ocular G-protein coupled receptors. The high prevalence of β2-agAAb in serum and AH samples of patients with POAG or SOAG suggests a common role of these AAbs in the etiopathogenesis of glaucoma, independent of open-angle glaucoma subtype.

Highlights

Glaucoma is as neurodegenerative disease, one of the leading causes for blindness in the developing countries
Beta2-agAAbs were seen in 86% (POAG) and 78% (SOAG) of aqueous humor (AH) samples
primary open-angle (POAG) or secondary open-angle glaucoma (SOAG) suggests a common role of these AAbs in the etiopathogenesis of glaucoma, independent of open-angle glaucoma subtype

Summary

Introduction

Glaucoma is as neurodegenerative disease, one of the leading causes for blindness in the developing countries. Its pathogenesis is assumed to be multifactorial with an increased intraocular pressure (IOP) as main risk factor. All patients show a disease progression despite an optimal level of IOP [1]. It is general accepted that several other factors are involved in the complex multifactorial pathophysiology of glaucoma. In addition to vascular dysregulation [2], oxidative stress [3,4,5], and abnormalities of the lamina cribrosa [6] and the trabecular meshwork [7], the involvement of autoimmune mechanisms [8,9,10] are seen as risk factors

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