Elevated Serum Mannose-Binding Lectin Levels Are Associated with Poor Outcome After Acute Ischemic Stroke in Patients with Type 2 Diabetes

Abstract

The activation of the complement system may be involved in the pathology of stroke and type 2 diabetes (T2DM). We therefore evaluated the long-term prognostic value of early measurement of serum mannose-binding lectin (MBL) levels, an activator of the complement system, in Chinese T2DM with acute ischemic stroke (AIS). Serum MBL levels were determined in T2DM patients with AIS (N = 188). The adjudicated end points were 1-year functional outcomes and mortality. The prognostic value of MBL was compared with the National Institutes of Health Stroke Scale score and with other known outcome predictors. Patients with an unfavorable outcomes and nonsurvivors had significantly increased MBL levels on admission (P < 0.0001 and P < 0.0001). Multivariate logistic regression analysis adjusted for common risk factors showed that MBL was an independent predictor of functional outcome (odds ratio (OR) = 8.99, 95% CI 2.21-30.12) and mortality (OR = 13.22, 95% CI 2.05-41.21). The area under the receiver operating characteristic curve of MBL was 0.75 (95% CI 0.68-0.83) for functional outcome and 0.85 (95% CI 0.80-0.90) for mortality. In type 2 diabetic patients with stroke, high levels of MBL predict future functional outcomes and mortality. This indicated that the elevated MBL levels may play a significant role in the pathology of the subsequent damage and that the pathways leading to complement activation warrant further exploration as potential therapeutic targets to improve the prognosis for these patients.

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

“…They also vary within individuals across time as a result of injury associated LP activation/consumption [ 1 , 2 , 4 , 16 ]. Experimental and clinical evidence implicates a clear role of the LP in the progression of brain damage in stroke, and the data are consistent with an association of LP activation with unfavorable outcome [ 1 , 14 , 15 , 17 – 19 ], with a few studies highlighting MBL [ 20 , 21 ] and ficolin-3 [ 1 ] as independent predictors of outcome after ischemic stroke. The role of ficolin-1 and ficolin-2 has scarcely been studied [ 1 , 2 ].…”

“…The LP, now recognized to be at the crossroad between complement and coagulation, is known to be deeply involved in the pathophysiology of brain ischemic injury [ 1 , 2 , 14 , 15 , 17 , 20 , 21 , 36 ]. The present multicenter observational study shows that LP in plasma is already consumed 6 h following stroke, consistent with LP activation, and that among the LP initiators evaluated in this study, ficolin-1 is selectively related to an unfavorable outcome 3 months after ischemic stroke.…”

“…Genetically defined MBL deficiency has been associated with a better outcome after stroke [ 14 , 15 ]. Consistently, MBL production has been correlated with increased risk of acute stroke [ 36 ], morbidity, and mortality after stroke [ 20 , 21 ]. The circulating levels measured here, being the result of a balance between genetic and pathophysiological conditions, may conceal the actual relationship between MBL and stroke.…”

Mannan binding lectin-associated serine protease-2 (MASP-2) critically contributes to post-ischemic brain injury independent of MASP-1

“…The latter findings are supported by numerous recent publications, which underline the prominent role of the LP in the pathogenesis and progression of brain damage in a clinical context. In stroke patients, the LP was shown to be the relevant pathway in the progression of ischemic brain damage [12, 15–17] with studies highlighting MBL [18, 19] and ficolin-3 [15], two different LP recognition molecules, as independent predictors of ischemic stroke outcome.…”

Elevated Serum Levels of CXC Chemokine Ligand-12 Are Associated with Unfavorable Functional Outcome and Mortality at 6-Month Follow-up in Chinese Patients with Acute Ischemic Stroke

“…Approximately 15 to 30 % of stroke survivors will be permanently disabled. China has 2.5 million new stroke cases each year and 7.5 million stroke survivors, and it causes a tremendous burden on health resources in China [2]. Prediction of outcome at stroke onset based on clinical deficits only is difficult; therefore, rapid measurement of blood biomarkers predicting functional outcome and mortality could prove useful [3].…”