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Published on: July 25, 2011
Mannose-binding lectin deficiency is associated with smaller infarction size and favorable outcome in ischemic stroke
Michael Osthoff1, Mira Katan, Felix Fluri
1Laboratory of Clinical Immunology, Department of Biomedicine and Clinic for Internal Medicine, University Hospital Basel, Basel, Switzerland. mosthoff@uhbs.ch
Background:
The Mannose-binding lectin (MBL) pathway of complement plays a pivotal role in the pathogenesis of ischemia/reperfusion (I/R) injury after experimental ischemic stroke. As comparable data in human ischemic stroke are limited, we investigated in more detail the association of MBL deficiency with infarction volume and functional outcome in a large cohort of patients receiving intravenous thrombolysis or conservative treatment.
Methodology/Principal Findings:
In a post hoc analysis of a prospective cohort study, admission MBL concentrations were determined in 353 consecutive patients with an acute ischemic stroke of whom 287 and 66 patients received conservative and thrombolytic treatment, respectively. Stroke severity, infarction volume, and functional outcome were studied in relation to MBL concentrations at presentation to the emergency department. MBL levels on admission were not influenced by the time from symptom onset to presentation (p = 0.53). In the conservative treatment group patients with mild strokes at presentation, small infarction volumes or favorable outcomes after three months demonstrated 1.5 to 2.6-fold lower median MBL levels (p = 0.025, p = 0.0027 and p = 0.046, respectively) compared to patients with more severe strokes. Moreover, MBL deficient patients (<100 ng/ml) were subject to a considerably decreased risk of an unfavorable outcome three months after ischemic stroke (adjusted odds ratio 0.38, p<0.05) and showed smaller lesion volumes (mean size 0.6 vs. 18.4 ml, p = 0.0025). In contrast, no association of MBL concentration with infarction volume or functional outcome was found in the thrombolysis group. However, the small sample size limits the significance of this observation.
Conclusions:
MBL deficiency is associated with smaller cerebral infarcts and favorable outcome in patients receiving conservative treatment. Our data suggest an important role of the lectin pathway in the pathophysiology of cerebral I/R injury and might pave the way for new therapeutic interventions.
Insights
Mannose-binding lectin (MBL) deficiency is linked to smaller stroke infarcts and better outcomes in patients not receiving thrombolysis. This suggests the lectin pathway
Area of Science:
- Immunology
- Neurology
- Complement System
Background:
- The Mannose-binding lectin (MBL) pathway is crucial in experimental ischemia/reperfusion (I/R) injury after stroke.
- Limited human data exist on MBL's role in ischemic stroke pathogenesis, infarction volume, and functional outcomes.
Purpose of the Study:
- To investigate the association between MBL deficiency and infarction volume in human ischemic stroke.
- To examine the relationship between MBL levels and functional outcomes in ischemic stroke patients.
- To compare these associations in patients receiving conservative versus thrombolytic treatment.
Main Methods:
- Post hoc analysis of a prospective cohort study involving 353 acute ischemic stroke patients.
- Measurement of MBL concentrations at hospital admission.
- Assessment of stroke severity, infarction volume, and functional outcome at three months.
Main Results:
- In patients receiving conservative treatment, lower MBL levels correlated with milder strokes, smaller infarcts, and favorable outcomes.
- MBL-deficient patients (<100 ng/ml) had significantly reduced risk of unfavorable outcomes (aOR 0.38) and smaller lesion volumes (0.6 vs. 18.4 ml).
- No significant association between MBL levels and outcomes was observed in the thrombolysis group, likely due to small sample size.
Conclusions:
- MBL deficiency is associated with reduced cerebral infarct size and improved functional outcomes in conservatively treated ischemic stroke patients.
- These findings highlight the lectin pathway's role in cerebral I/R injury pathophysiology.
- The results may inform the development of novel therapeutic strategies targeting the MBL pathway.
