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

Hohberger, Bettina; Kunze, Rudolf; Wallukat, Gerd; Kara, Katja; Mardin, Christian Y.; Laemmer, Robert; Schlötzer‐Schrehardt, Ursula; Hosari, Sami; Horn, Folkert K.; Muñoz, Luis; Herrmann, Martin

doi:10.3389/fimmu.2019.02112

Cited by 13 publications

(32 citation statements)

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“…Statistics: all POAG against all SOAG p = 0.035; all AH against sera p = 0.96; POAG AH against sera p = 0.09; SOAG AH against sera p = 0.047; AH POAG against SOAG p = 0.003; sera POAG against SOAG p = 0.727. Up to now, the b2-agAAbs were observed in sera of patients with OAG (12). The presence of these specific agonistic AAb in AH might support the above mentioned hypothesis of a regulatory capability of IOP by the local b2-agAAb.…”

Section: Discussionsupporting

confidence: 70%

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

et al. 2021

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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.

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Section: Discussionsupporting

confidence: 70%

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

et al. 2021

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“…This was a surprising unexpected effect. In healthy controls, which are included in many studies, these autoantibodies are only found in a small percentage [ 37 , 38 ]”.…”

Section: Resultsmentioning

confidence: 99%

Functional autoantibodies against G-protein coupled receptors in patients with persistent Long-COVID-19 symptoms

Wallukat

Hohberger

Wenzel

et al. 2021

Journal of Translational Autoimmunity

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Impairment of health after overcoming the acute phase of COVID-19 is being observed more and more frequently. Here different symptoms of neurological and/or cardiological origin have been reported. With symptoms, which are very similar to the ones reported but are not caused by SARS-CoV-2, the occurrence of functionally active autoantibodies ( f AABs) targeting G-protein coupled receptors (GPCR- f AABs) has been discussed to be involved. We, therefore investigated, whether GPCR- f AABs are detectable in 31 patients suffering from different Long-COVID-19 symptoms after recovery from the acute phase of the disease. The spectrum of symptoms was mostly of neurological origin (29/31 patients), including post-COVID-19 fatigue, alopecia, attention deficit, tremor and others. Combined neurological and cardiovascular disorders were reported in 17 of the 31 patients. Two recovered COVID-19 patients were free of follow-up symptoms. All 31 former COVID-19 patients had between 2 and 7 different GPCR- f AABs that acted as receptor agonists. Some of those GPCR- f AABs activate their target receptors which cause a positive chronotropic effect in neonatal rat cardiomyocytes, the read-out in the test system for their detection (bioassay for GPCR- f AAB detection). Other GPCR- f AABs, in opposite, cause a negative chronotropic effect on those cells. The positive chronotropic GPCR- f AABs identified in the blood of Long-COVID patients targeted the β 2 -adrenoceptor (β 2 - f AAB), the α 1 -adrenoceptor (α 1 - f AAB), the angiotensin II AT1-receptor (AT1- f AAB), and the nociceptin—like opioid receptor (NOC- f AAB). The negative chronotropic GPCR- f AABs identified targeted the muscarinic M 2 -receptor (M 2 - f AAB), the MAS-receptor (MAS- f AAB), and the ETA-receptor (ETA- f AAB). It was analysed which of the extracellular receptor loops was targeted by the autoantibodies.

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“…Thus, all factors influencing pericytes (e.g. autonomic nervous system, antibodies against adrenergic receptors) [52] and mechanical environmental alterations (e.g. shear or tensile forces [53]) may be able to influence capillary microcirculation.…”

Section: Plos Onementioning

confidence: 99%

OCT-angiography: Regional reduced macula microcirculation in ocular hypertensive and pre-perimetric glaucoma patients

Hohberger

Lucio²,

Schlick³

et al. 2021

PLoS ONE

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Purpose OCT-angiography (OCT-A) offers a non-invasive method to visualize retinochoroidal microvasculature. As glaucoma disease affects retinal ganglion cells in the macula, macular microcirculation is of interest. The purpose of the study was to investigate regional macular vascular characteristics in patients with ocular hypertension (OHT), pre-perimetric primary open-angle glaucoma (pre-POAG) and controls by OCT-A in three microvascular layers. Material and methods 180 subjects were recruited from the Erlangen Glaucoma Registry, the Department of Ophthalmology, University of Erlangen and residents: 38 OHT, 20 pre-POAG, 122 controls. All subjects received an ophthalmological examination including measurements of retinal nerve fibre layer (RNFL), retinal ganglion cell layer (RGC), inner nuclear layer (INL), and Bruch’s Membrane Opening-Minimum Rim Width (BMO-MRW). Macular vascular characteristics (vessel density, VD, foveal avascular zone, FAZ) were measured by OCT-A (Spectralis OCT II) in superficial vascular plexus (SVP), intermediate capillary plexus (ICP), and deep capillary plexus (DCP). Results With age correction of VD data, type 3 tests on fixed effects showed a significant interaction between diagnosis and sectorial VD in SVP (p = 0.0004), ICP (p = 0.0073), and DCP (p = 0.0003). Moreover, a significance in sectorial VD was observed within each layer (p<0.0001) and for the covariate age (p<0.0001). FAZ differed significantly between patients’ groups only in ICP (p = 0.03), not in SVP and DCP. For VD the AUC values of SVP, ICP, and DCP were highest among diagnostic modalities (AUC: 0.88, 95%-CI: 0.75–1.0, p<0.001). Conclusion Regional reduced macula VD was observed in all three retinal vascular layers of eyes with OHT and pre-POAG compared to controls, indicating localized microvascular changes as early marker in glaucoma pathogenesis.

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

Cited by 13 publications

References 40 publications

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

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

Functional autoantibodies against G-protein coupled receptors in patients with persistent Long-COVID-19 symptoms

OCT-angiography: Regional reduced macula microcirculation in ocular hypertensive and pre-perimetric glaucoma patients

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