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

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

JOURNAL=Frontiers in Immunology

VOLUME=12

YEAR=2021

URL=https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2021.550236

DOI=10.3389/fimmu.2021.550236

ISSN=1664-3224

ABSTRACT=<sec><title>Purpose</title><p>Agonistic <italic>β</italic>2-adrenergic receptor autoantibodies (<italic>β</italic>2-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 <italic>β</italic>2-agAAb in aqueous humor (AH) samples of OAG patients and to correlate these with the corresponding <italic>β</italic>2-agAAb serum data.</p></sec><sec><title>Material and Methods</title><p>Thirty-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 <italic>β</italic>2-agAAb by a bioassay quantifying the beating rate of cultured cardiomyocyte (cut-off: 2 U).</p></sec><sec><title>Results</title><p>Thirty-six of 39 (92.3%) and 34 of 39 (87.2%) of OAG patients showed a <italic>β</italic>2-agAAb in their sera and AH samples, respectively. All <italic>β</italic>2-agAAb AH-positive OAG patients were also seropositive. We also observed a <italic>β</italic>2-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 <italic>β</italic>2-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 <italic>β</italic>2-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.</p></sec><sec><title>Conclusion</title><p>The detection of <italic>β</italic>2-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 <italic>β</italic>2-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.</p></sec>