Autoantibodies targeting G protein-coupled receptors: An evolving history in autoimmunity. Report of the 4th international symposium

Cabral-Marques, Otávio; Moll, Guido; Catar, Rusan; Preuß, B.; Bankamp, Lukas; Pecher, Ann-Christin; Henes, Joerg; Klein, Reinhild; Kamalanathan, A.S.; Akbarzadeh, Reza; Oostveen, Wieke van; Hohberger, Bettina; Endres, Matthias; Koolmoes, Bryan; Levarht, N.; Postma, Rudmer; Duinen, Vincent van; Zonneveld, Anton Jan van; Vries‐Bouwstra, Jeska de; Fehres, Cynthia M.; Tran, Florian; Vale, Fernando Yuri Nery do; Souza, Kamilla Batista da Silva; Filgueiras, Igor Salerno; Schimke, Lena F.; Baiocchi, G.; Miranda, Gustavo Cabral de; Fonseca, Dennyson Leandro M.; Freire, Paula Paccielli; Hackel, Alexander; Graßhoff, Hanna; Stähle, Anja; Müller, Antje; Dechend, Ralf; Yu, Xinhua; Petersen, Frank; Sotzny, Franziska; Sakmar, Thomas P.; Ochs, Hans D.; Schulze‐Forster, Kai; Heidecke, Harald; Scheibenbogen, Carmen; Shoenfeld, Yehuda; Riemekasten, Gabriela

doi:10.1016/j.autrev.2023.103310

Cited by 24 publications

(26 citation statements)

References 122 publications

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“…[20 ▪ ] showed that the vasocontractile response of endothelial cells to angiotensin II and endothelin-1 (ET-1) was amplified by IgG from SSc patients with SRC through substantial crosstalk between AT1R and ETAR. AT1R and ETAR belong to a family of G-protein coupled receptors (GPCRs), which are now recognized as preferential autoantibody targets in patients with SSc and other autoimmune diseases [21]. A recent study found that autoantibodies against the members of another GPCR family, receptors of the bioactive lipid mediator sphingosine-1-phosphate (S1P), which regulate vasoconstriction, lymphocyte trafficking, and vascular remodeling, were elevated in patients with SSc, especially in those with PAH [22].…”

Section: Vascular Injurymentioning

confidence: 99%

Pathogenesis of vasculopathy in systemic sclerosis and its contribution to fibrosis

Kawaguchi

Kuwana

2023

Current Opinion in Rheumatology

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Purpose of review In patients with systemic sclerosis (SSc), vascular manifestations precede skin and organ fibrosis. There is increasing evidence demonstrating a pathogenic link between early vascular injury and subsequent development of tissue fibrosis. Recent findings Our knowledge of cellular and molecular mechanisms underlying a unique relationship between SSc-related vasculopathy and fibrosis has changed over the last few years. There is increasing evidence showing viral infection as a potential trigger elucidating vascular injury. Due to defective vascular repair machinery, this initial event results in endothelial cell activation and apoptosis as well as the recruitment of inflammatory/immune cells, leading to endothelial-to-mesenchymal transition. This sequential process induces destructive vasculopathy in capillaries, fibroproliferative vascular lesions in arteries, and excessive fibrosis in the surrounding tissue. A variety of molecular mechanisms and pathways involved in vascular remodeling linked to subsequent excessive fibrosis have been identified and serve as attractive therapeutic targets for SSc. Summary Endothelial injury may play a central role in connecting three features that characterize SSc pathogenesis: vasculopathy, chronic inflammation, and fibrosis. Our understanding of the processes responsible for myofibroblast differentiation triggered by vascular injury will provide the rationale for novel targeted therapies for SSc.

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Section: Vascular Injurymentioning

confidence: 99%

Pathogenesis of vasculopathy in systemic sclerosis and its contribution to fibrosis

Kawaguchi

Kuwana

2023

Current Opinion in Rheumatology

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“…Non-traditional risk factors include mode of donor brain death, cytomegalovirus infection, HLA mismatch, and HLA-antibody-mediated rejection. In addition, non-HLA antibodies are now recognized as a potential source of antibody-mediated rejection following transplantation [ 26 , 27 ]. The intricate role of non-HLA antibodies in allograft rejection and vasculopathy has been described in our earlier studies [ 27 , 28 , 29 , 30 , 31 , 32 , 33 ].…”

Section: Introductionmentioning

confidence: 99%

“…In addition, non-HLA antibodies are now recognized as a potential source of antibody-mediated rejection following transplantation [ 26 , 27 ]. The intricate role of non-HLA antibodies in allograft rejection and vasculopathy has been described in our earlier studies [ 27 , 28 , 29 , 30 , 31 , 32 , 33 ]. The epitopes that lead to the production of these antibodies typically result from tissue disruption, specifically of the endothelium, secondary to prior inflammation and injury [ 29 , 34 ].…”

Section: Introductionmentioning

confidence: 99%

“…The epitopes that lead to the production of these antibodies typically result from tissue disruption, specifically of the endothelium, secondary to prior inflammation and injury [ 29 , 34 ]. Interestingly, most non-HLA antibodies are also considered to be autoantibodies [ 27 , 35 , 36 , 37 , 38 ], as they are often directed against cryptic autoantigens of vascular endothelium, which are expressed following both transplant and vascular injury.…”

Section: Introductionmentioning

confidence: 99%

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Nailfold Videocapillaroscopy for Non-Invasive Assessment of Microcirculation and Prognostic Correlation with Endothelial Dysfunction, Cardiovascular Risk Factors, and Non-HLA Antibodies in Heart Transplant Recipients: A Pilot Study

Sikorska

Kamińska

Catar

et al. 2023

JCM

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Early identification of allograft vasculopathy and the concomitant elimination of adverse risk factors is essential for improving the long-term prognosis of heart transplant (HTx) recipients with underlying cardiovascular disease (CVD). The major aim of this pilot study was to conduct a non-invasive imaging evaluation of the HTx patient microcirculation by employing nailfold video-capillaroscopy (NVC) in a well-characterized patient and control cohort, and to correlate these data with endothelial cell function, accompanied by studies of traditional cardiovascular risk factors and non-HLA antibodies in HTx recipients. Ten patients undergoing HTx (mean age of 38 ± 14 years) were recruited for the study and compared to a control group of 12 well-matched healthy volunteers (mean age 35 ± 5 years) with normal body mass index (BMI). Detailed medical records were collected from all individuals. NVC was performed using CapillaryScope 200 MEDL4N microscope. For functional readout and correlation analysis, endothelial cell network formation in conjunction with measurements of patient serum levels of vascular endothelial growth factor (VEGF) and non-HLA autoantibodies directed against the angiotensin II type-1-receptor (anti-AT1R-Ab), endothelin-1 type-A-receptor (anti-ETAR-Ab), protease-activated receptor-1 (anti-PAR-1-Ab), and VEGF-A (anti-VEGF-A-Ab) were studied. Our NVC analysis found that the average apical loop diameter of nailfold capillaries was significantly increased in HTx recipients (p = 0.001). In addition, HTx patients with more prominent changes in capillaroscopic patterns were characterized by the presence of traditional cardiovascular risk factors, and HTx patients had increased levels of anti-AT1R-ab, anti-ETAR-ab, and anti-VEGF-A-Ab (p = 0.017, p = 0.025, and p = 0.003, respectively). Capillary diameters most strongly correlated with elevated serum levels of troponin T and triglycerides (R = 0.69, p = 0.028 and R = 0.81, p = 0.004, respectively). In conclusion, we found that an abnormal NVC pattern in HTx patients is associated with traditional CVD risk factors and that NVC is a useful non-invasive tool to conveniently monitor changes in the microvasculature of HTx patients.

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“…Functional autoantibodies can target endothelial antigens as well as circulating proteins (eg, cytokines, growth factors) via variable antigen region–specific interactions and impact vasoregulation. 1 , 2 Agonistic autoantibodies directed against G‐protein–coupled receptors (GPCRs), for example, antibodies against the angiotensin II receptor 1 (AT1R) or the endothelin‐1 type A receptor (ETAR), are typically encountered in vascular diseases and well known to affect cardiovascular function (eg, dysregulation of blood pressure). 2 , 3 …”

mentioning

confidence: 99%

Vasoregulatory Autoantibodies and Clinical Outcome After Ischemic Stroke—PROSCIS‐B

Liman,

Siegerink,

Piper

et al. 2023

JAHA

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Background Vasoregulatory autoantibodies including autoantibodies targeting G‐protein–coupled receptors might play a functional role in vascular diseases. We investigated the impact of vasoregulatory autoantibodies on clinical outcome after ischemic stroke. Methods and Results Data were used from the PROSCIS‐B (Prospective Cohort With Incident Stroke–Berlin). Autoantibody‐targeting receptors such as angiotensin II type 1 receptor (AT1R), endothelin‐1 type A receptor, complement factor‐3 and ‐5 receptors, vascular endothelial growth factor receptor‐1 and ‐2, vascular endothelial growth factor A and factor B were measured. We explored associations of high antibody levels with (1) poor functional outcome defined as modified Rankin Scale >2 or Barthel Index <60 at 1 year after stroke, (2) Barthel Index scores over time using general estimating equations, and (3) secondary vascular events (recurrent stroke, myocardial infarction) or death up to 3 years using Cox proportional hazard models. We included 491 patients with ischemic stroke with data on autoantibody levels and outcome. In models adjusted for demographics and vascular risk factors, high autoantibody concentrations (quartile 4) targeting complement factor C3a receptor, vascular endothelial growth factor receptor‐2, and vascular endothelial growth factor B were associated with poor functional outcome at 1 year: (odds ratio, 2.0 [95% CI, 1.1–3.6]; odds ratio, 1.8 [95% CI, 1.1–3.2]; and odds ratio, 2.1 [95% CI, 1.2–3.6], respectively) and with lower Barthel Index scores over 3 years (complement factor C3a receptor: adjusted β=−3.3 [95% CI, −5.7 to −0.5]; VEGF‐B: adjusted β=−2.4 [95% CI, −4.8 to −0.06]). Patients with high autoantibody levels were not at higher risk for secondary vascular events or death. Conclusions High levels of autoantibodies against vascular endothelial growth factor receptor‐2, vascular endothelial growth factor B, and complement factor C3a receptor measured are associated with poor functional outcome after stroke but not with recurrent vascular events or death. Registration URL: https://www.clinicaltrials.gov ; Unique identifier: NCT01363856.

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Autoantibodies targeting G protein-coupled receptors: An evolving history in autoimmunity. Report of the 4th international symposium

Cited by 24 publications

References 122 publications

Pathogenesis of vasculopathy in systemic sclerosis and its contribution to fibrosis

Pathogenesis of vasculopathy in systemic sclerosis and its contribution to fibrosis

Nailfold Videocapillaroscopy for Non-Invasive Assessment of Microcirculation and Prognostic Correlation with Endothelial Dysfunction, Cardiovascular Risk Factors, and Non-HLA Antibodies in Heart Transplant Recipients: A Pilot Study

Vasoregulatory Autoantibodies and Clinical Outcome After Ischemic Stroke—PROSCIS‐B

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