Abstract
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.
| Original language | English |
|---|---|
| Article number | e032441 |
| Journal | Journal of the American Heart Association |
| Volume | 12 |
| Issue number | 23 |
| DOIs | |
| Publication status | Published - 05.12.2023 |
Funding
The PROSCIS-B study received funding from the Federal Ministry of Education and Research via the grant Center for Stroke Research Berlin (01 EO 0801) until May 2018. Dr Liman received grant support from the German Research Foundation. Dr Elkind received personal compensation from Merck/Organon for expert witness testimony related to hormonal contraception and stroke and from UpToDate for chapters related to stroke, outside submitted work. Dr Heuschmann received research grants from the German Ministry of Research and Education, German Research Foundation, European Union, Charité, Berlin Chamber of Physicians, German Parkinson Society, University Hospital Würzburg, Robert-Koch-Institute, German Heart Foundation, and Federal Joint Committee within the Innovationfond. Dr Endres received grant support from Bayer, the German Research Foundation, the German Federal Ministry of Education and Research, the German Center for Neurodegenerative Diseases, the German Centre for Cardiovascular Research, the European Union, Corona Foundation, and Fondation Leducq. Dr Endres reports funding from the DFG via KFO 5023 Because-Y, project 2 EN343/16-1. The remaining authors have no disclosures to report.
Research Areas and Centers
- Academic Focus: Center for Infection and Inflammation Research (ZIEL)
DFG Research Classification Scheme
- 2.22-18 Rheumatology
- 2.21-05 Immunology
