Differential associations of low vs. high levels of several GPCR-directed regulatory autoantibodies with stroke etiology, functional outcome, and recurrent vascular risk suggest potential roles in stroke pathophysiology.
Key Findings
Results
High levels of alpha2-adrenoceptor autoantibodies (Q4 vs. Q1-Q3) were associated with worse functional outcome at 12 months after ischemic stroke.
Odds ratio for worse modified Rankin Scale outcome at one year: OR=1.49; 95% CI=1.02-2.18
Functional outcome was assessed using ordinal logistic regression with the Modified Rankin Scale (mRS) at one year
562 patients were included (mean age 67, SD=13; 38% female) from the PROSCIS-B cohort
Blood samples were collected within seven days of first-ever stroke and RABs measured by ELISA (CellTrend)
Results
High levels of endothelin B receptor autoantibodies (ETB-abs, Q4 vs. Q1-Q3) were associated with worse functional outcome at 12 months after ischemic stroke.
Odds ratio for worse mRS outcome at one year: OR=1.49; 95% CI=1.02-2.18
The association mirrored that seen with alpha2-antibodies, sharing identical OR and CI values
Outcome assessed by ordinal logistic regression using the Modified Rankin Scale at one year
High RAB level defined as quartile 4 compared to the reference group of quartiles 1-3
Results
Low levels of AT2 (angiotensin II receptor type 2) autoantibodies (Q1 vs. Q2-Q4) were associated with higher recurrent cardiovascular risk over three years.
Hazard ratio for combined endpoint (stroke, myocardial infarction, death): HR=1.86; 95% CI=1.22-2.86
Risk assessed using Cox proportional hazard models over a three-year follow-up period
Combined endpoint included stroke, myocardial infarction, and death
Low RAB level defined as quartile 1 compared to the reference group of quartiles 2-4
Results
Low levels of alpha2-adrenoceptor autoantibodies (Q1 vs. Q2-Q4) were associated with higher recurrent cardiovascular risk over three years.
Hazard ratio for combined endpoint (stroke, myocardial infarction, death): HR=1.77; 95% CI=1.15-2.72
Risk assessed using Cox proportional hazard models over three years of follow-up
This finding indicates that both high and low levels of alpha2-abs showed associations with adverse outcomes, but in different domains (functional outcome vs. recurrent vascular risk)
Results
Low levels of beta1-adrenoceptor autoantibodies (Q1 vs. Q2-Q4) were associated with higher recurrent cardiovascular risk over three years.
Hazard ratio for combined endpoint (stroke, myocardial infarction, death): HR=1.58; 95% CI=1.03-2.44
Risk assessed using Cox proportional hazard models over three years of follow-up
Combined endpoint included stroke, myocardial infarction, and death
Results
All measured GPCR-directed regulatory autoantibodies showed a pattern of more large artery atherosclerosis (LAA) stroke in the lowest quartile (Q1) and more cardioembolic (CE) stroke in the highest quartile (Q4).
This pattern was observed across all seven autoantibodies measured: anti-α1, anti-α2, anti-β1, anti-β2, endothelin B receptor, angiotensin II receptor type 2, and CXCR3 receptor antibodies
Quartile subgroups were characterized at baseline
This suggests a differential relationship between RAB levels and stroke etiology
RABs were measured from sera collected within seven days of first-ever stroke
Methods
The study cohort comprised 562 patients from the Prospective Cohort with Incident Stroke Berlin (PROSCIS-B) with a mean age of 67 years and 38% female participants.
Mean age was 67 years (SD=13)
38% of participants were female
Data were derived from PROSCIS-B (NCT01363856)
All patients had first-ever ischemic stroke
GPCR regulatory autoantibodies (RABs) were measured by ELISA (CellTrend) from sera collected within seven days of stroke onset
What This Means
This research suggests that proteins called regulatory autoantibodies — which the body produces and which target specific receptors involved in controlling blood pressure, blood vessels, and immune responses — may play a role in recovery and long-term outcomes after a stroke. Researchers measured seven different types of these autoantibodies in blood samples taken within one week of stroke from 562 patients in Berlin, then tracked patient outcomes for up to three years. They found that patients with the highest levels of two specific autoantibodies (targeting alpha2-adrenoceptors and endothelin B receptors) had worse physical functioning one year after their stroke, while patients with the lowest levels of three autoantibodies (targeting alpha2-adrenoceptors, beta1-adrenoceptors, and angiotensin II receptors) faced nearly double the risk of having another stroke, heart attack, or dying within three years.
Interestingly, the research also found that across all seven autoantibodies studied, patients in the lowest antibody level group tended to have strokes caused by large artery disease (like narrowed arteries), while patients in the highest level group were more likely to have strokes caused by blood clots traveling from the heart. This pattern across all antibody types suggests these molecules may reflect or influence the underlying biological mechanisms of different stroke types.
This research suggests that measuring these autoantibodies after a stroke could potentially help identify patients at higher risk for poor recovery or future cardiovascular events. However, this is an observational study, meaning it shows associations rather than proving cause and effect, and more research would be needed to understand whether these autoantibodies directly cause harm or are simply markers of underlying disease processes.