Autoantibodies targeting G protein-coupled receptors and clinical outcome after ischemic stroke (PROSCIS-B)

G protein-coupled receptor (GPCR) directed regulatory autoantibodies (RABs) have previously been linked to poor functional outcome after ischemic stroke. We investigated the impact of anti-α1/α2/β1/β2 receptor, endothelin B receptor, angiotensin II receptor type 2, and CXCR3 receptor directed RABs on functional outcome and recurrent events after ischemic stroke.

Data were derived from the Prospective Cohort with Incident Stroke Berlin (PROSCIS-B; NCT01363856). RABs were measured by ELISA (CellTrend) from sera collected within seven days of first-ever stroke. High RAB levels (quartile [Q]4 vs. Q1-3) and low levels (Q1 vs. Q2-4) were compared to reference groups. Quartile subgroups were characterized at baseline. Functional outcome, measured by the Modified Rankin Scale (mRS) at one year, was evaluated with ordinal logistic regression. Cox proportional hazard models were used to assess risk for a combined endpoint (stroke, myocardial infarction, death) over three years.

562 patients were included (mean age 67 (SD= 13); 38% female). All RABs showed more large artery atherosclerosis (LAA) stroke in Q1, while cardioembolic strokes (CE) were more frequent in Q4. Worse functional outcome at 12 months was associated with high levels (Q4) of alpha2-antibodies (abs) (OR=1.49; 95%CI=1.02-2.18) and ETB-abs (OR=1.49; 95%CI=1.02-2.18) vs. Q1-Q3. Recurrent cardiovascular risk over three years was higher with low levels (Q1) of AT2-abs (HR=1.86; 95%CI=1.22-2.86), alpha2-abs (HR=1.77; 95%CI=1.15-2.72), and beta1-abs (HR=1.58; 95%CI=1.03-2.44) vs. Q2-Q4.

Differential associations of low vs. high levels of several RABs with stroke etiology, functional outcome, and recurrent vascular risk suggest potential roles in stroke pathophysiology.