Early ficolin-1 is a sensitive prognostic marker for functional outcome in ischemic stroke

Abstract

BackgroundSeveral lines of evidence support the involvement of the lectin pathway of complement (LP) in the pathogenesis of acute ischemic stroke. The aim of this multicenter observational study was to assess the prognostic value of different circulating LP initiators in acute stroke.MethodsPlasma levels of the LP initiators ficolin-1, -2, and -3 and mannose-binding lectin (MBL) were measured in 80 stroke patients at 6 h only and in 85 patients at 48 h and later. Sixty-one age- and sex-matched healthy individuals served as controls. Stroke severity was measured on admission using the National Institutes of Health Stroke Scale (NIHSS). The outcome was measured at 90 days by the modified Rankin Scale (mRS).ResultsFicolin-1 was decreased in patients compared with controls measured at 6 h (median 0.13 vs 0.33 μg/ml, respectively, p < 0.0001). At 48 h, ficolin-1 was significantly higher (0.45 μg/ml, p < 0.0001) compared to the 6 h samples and to controls. Likewise, ficolin-2 was decreased at 6 h (2.70 vs 4.40 μg/ml, p < 0.0001) but not at 48 h. Ficolin-3 was decreased both at 6 and 48 h (17.3 and 18.23 vs 21.5 μg/ml, p < 0.001 and <0.05, respectively). For MBL no difference was detected between patients and controls or within patients at the different time points. In multivariate analysis, early ficolin-1 was independently associated with unfavorable mRS outcome (adjusted odds ratio (OR): 2.21, confidence interval (CI) 95 % 1.11–4.39, p = 0.023). Early ficolin-1 improved the discriminating ability of an outcome model including NIHSS and age (area under the curve (AUC) 0.95, CI 95 % 0.90–0.99, p = 0.0001).ConclusionsThe ficolins are consumed within 6 h after stroke implicating activation of the LP. Early ficolin-1 is selectively related to 3-month unfavorable outcome.Electronic supplementary materialThe online version of this article (doi:10.1186/s12974-016-0481-2) contains supplementary material, which is available to authorized users.

Lectin Pathway of Complement Activation Is Associated with Vulnerability of Atherosclerotic Plaques

“…This observation is in line with a previous work by our group reporting that ficolin-1 is a sensitive prognostic marker for stroke patients (19), and further implicates ficolin-1 in acute brain injury.…”

Injury site‐specific targeting of complement inhibitors for treating stroke

“…Indeed, in human stroke, serum levels of MBL were shown to be an independent risk factor of ischemic stroke, 36 and genetically defined deficiency of serum MBL results in smaller lesion sizes and more favorable acute (3 days) and sub-acute outcomes (3 months) in stroke patients. [37][38][39][40] Similarly, lower serum levels of ficolin-3 on patient admission, which is indicative of ficolin consumption, correlated with increased injury markers and worse functional outcome in stroke patients. 41 Although the lectin pathway appears to play an important role in complement activation after cerebral ischemia, we have shown an equally important role for the alternative pathway in the propagation of injury following murine ischemic stroke, since genetic or pharmacological inhibition of the alternative pathway also resulted in a significant reduction in complement activation and improved outcomes after stroke.…”

“…Since MBL deficient mice, but not C1q deficient mice are protected from ischemic stroke, the data taken together indicate that complement activation and propagation of injury in murine ischemic stroke occurs via IgM mediated activation of the lectin pathway. Indeed, in human stroke, serum levels of MBL were shown to be an independent risk factor of ischemic stroke, and genetically defined deficiency of serum MBL results in smaller lesion sizes and more favorable acute (3 days) and sub‐acute outcomes (3 months) in stroke patients . Similarly, lower serum levels of ficolin‐3 on patient admission, which is indicative of ficolin consumption, correlated with increased injury markers and worse functional outcome in stroke patients …”

Serotonergic Regulation and Cognition after Stroke: The Role of Antidepressant Treatment and Genetic Variation

“…A multitude of factors may affect stroke outcome ranging from inflammation to vascular risk factors [23,24] and the assessment of stroke patients should be multifaceted. The current results may imply that also genetic fac- tors should be taken into account when developing and improving prognostic algorithms with the potential to guide a personalized treatment approach.…”