Plasma biomarkers in patients with familial cavernous malformation and their first-degree relatives

TL;DR

The study identifies plasma biomarkers that distinguish patients with familial cerebral cavernous malformations from their healthy relatives and those with severe disease.

Contribution

Novel plasma biomarkers (CD31, BDNF, serpin E1/PAI-1, ROBO4) are identified for FCCM and severe CDA.

Findings

Low CD31 and BDNF levels are independent risk factors for FCCM.

Low serpin E1/PAI-1 and high ROBO4 levels are linked to severe CDA in FCCM patients.

Combining CD31 and BDNF provides high accuracy in distinguishing FCCM patients from healthy relatives.

Abstract

We aimed to explore the differences in plasma biomarker levels between patients with familial cerebral cavernous malformations (FCCM) and their healthy first-degree relatives (FDRs) and between FCCM patients with and without severe chronic disease aggressiveness (CDA).

Magnetic resonance imaging (MRI) scanning and genetic testing was performed in patients with multiple CCMs and their FDRs. Sixty-seven plasma biomarkers were tested using a customised multiplex bead immunoassay kit. Univariate and multivariate unconditional logistic regression analyses were conducted to determine the associations between plasma factors and the risk of developing FCCM and severe CDA. Receiver operating characteristic (ROC) curves were generated for each independent risk factor.

Plasma factors of 37 patients with FCCM and 37 FDRs were examined. Low CD31 (P < 0.001) and BDNF levels (P = 0.013) were independent risk factors for FCCM. The best model was achieved by combining the results of CD31 and BDNF (AUC = 0.845, sensitivity 0.838, specificity 0.784, cutoff score − 4.295) to distinguish patients with FCCM from healthy FDRs. Low serpin E1/PAI-1 (P = 0.011) and high ROBO4 levels (P = 0.013) were independent risk factors for severe CDA in patients with FCCM. The best model was achieved by combining the results of E1/PAI-1 and ROBO4 levels (AUC = 0.913, sensitivity 1.000, specificity 0.760, cutoff score – 0.525) to identify patients with FCCM and severe CDA.

The plasma concentrations of CD31 and BDNF seem to be lower in patients with FCCM than in their healthy FDRs. Low serpin E1/PAI-1 and high ROBO4 concentrations may be correlated with high lesion burden and risk of recurrent bleeding.

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