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

Purpose Agonistic beta 2-adrenergic receptor autoantibodies (beta 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 beta 2-agAAb in aqueous humor (AH) samples of OAG patients and to correlate these with the corresponding beta 2-agAAb serum data. Material and Methods Thirty-nine patients (21 male, 18 female) were recruited from the Department of Ophthalmology, University of Erlangen-Nurnberg: twenty-one POAG, 18 SOAG. Aqueous humor samples were collected during minimal invasive glaucoma surgery. Serum and AH samples were analyzed for beta 2-agAAb by a bioassay quantifying the beating rate of cultured cardiomyocyte (cut-off: 2 U). Results Thirty-six of 39 (92.3%) and 34 of 39 (87.2%) of OAG patients showed a beta 2-agAAb in their sera and AH samples, respectively. All beta 2-agAAb AH-positive OAG patients were also seropositive. We also observed a beta 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 beta 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 beta 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. Conclusion The detection of beta 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 beta 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.

Automated summary

The presence of beta 2-agAAb was detected in 92.3% of OAG patients' sera and 87.2% of AH samples. The seropositivity for beta 2-agAAb in patients with POAG and SOAG was 95% and 89% respectively, with 86% (POAG) and 78% (SOAG) positive in AH samples. The adrenergic activity of beta 2-agAAb in the AH was higher in patients with POAG compared to those with SOAG.