Genetically Determined Serum Levels of Mannose-Binding Lectin Correlate Negatively with Common Carotid Intima-Media Thickness in Systemic Lupus Erythematosus

2010 ◽  
Vol 37 (9) ◽  
pp. 1815-1821 ◽  
Author(s):  
LONE N. TROELSEN ◽  
PETER GARRED ◽  
BURIS CHRISTIANSEN ◽  
CHRISTIAN TORP-PEDERSEN ◽  
SØREN JACOBSEN

Objective.Patients with systemic lupus erythematosus (SLE) have excess cardiovascular morbidity and mortality due to accelerated atherosclerosis that cannot be attributed to traditional cardiovascular risk factors alone. Variant alleles of the mannose-binding lectin gene (MBL2) causing low serum concentrations of functional mannose-binding lectin (MBL) are associated with SLE and development of atherosclerosis. Recent studies show that these variant alleles are associated with increased risk of arterial thrombosis and cardiovascular disease in patients with SLE. Intima-media thickness of the common carotid artery (ccIMT) is a validated noninvasive anatomic measure of subclinical atherosclerosis. In a cross-sectional study we examined the relation among ccIMT, MBL2 genotypes, and serum concentrations of MBL.Methods.The MBL2 extended genotypes (YA/YA, YA/XA, XA/XA, YA/YO, XA/YO, YO/YO) and serum concentrations of MBL were determined in 41 outpatients with SLE. ccIMT was measured by means of ultrasonography. Traditional and nontraditional cardiovascular risk modifiers were assessed and controlled for.Results.Using nonparametric Mann-Whitney tests we found a significant difference in ccIMT between low-expressing (XA/XA+YA/YO+XA/YO+YO/YO) and high-expressing (YA/YA+YA/XA) MBL2 genotypes (p = 0.034). The difference in ccIMT remained significant in multivariable analysis adjusting for traditional and nontraditional cardiovascular risk modifiers (p = 0.049). ccIMT was negatively correlated to serum concentrations of MBL (Spearman rho = −0.33, p = 0.037). This relation also remained significant in multivariable analysis (p = 0.042).Conclusion.In this group of SLE patients, MBL2 low-expressing genotypes and low serum levels of MBL were correlated with ccIMT, independent of the effects of traditional and nontraditional cardiovascular risk modifiers.

Lupus ◽  
2017 ◽  
Vol 27 (3) ◽  
pp. 372-379 ◽  
Author(s):  
J Z Cieslinski ◽  
T L Skare ◽  
R Nisihara ◽  
I J De Messias-Reason ◽  
S R R Utiyama

The complement system contributes to the pathogenesis of systemic lupus erythematosus (SLE). Mannose-binding lectin (MBL) is a key molecule of the lectin pathway of complement and seems to be related to the clinical manifestations of this disease. We evaluated the serum levels of MBL and its relationship with disease onset and clinical findings in SLE patients. Serum samples were analysed in 195 patients and 145 healthy controls from southern Brazil. Patients with high MBL levels (above 2000 ng/ml) showed a significant increase in the frequency of thrombocytopaenia ( p = 0.007; OR = 2.71; 95% CI = 1.32–5.55); and seizures ( p = 0.034; OR = 2.61; 95% CI = 1.07–6.37). A positive correlation between disease activity and MBL levels (>2000 ng/ml; p = 0.031, rho = 0.279) as well as of MBL concentration with accumulated organ damage ( p = 0.021; rho = 0.232) was observed. Our results suggest a role for MBL in the development of clinical manifestations such as thrombocytopaenia and seizures in SLE patients. These findings corroborate the participation of the lectin pathway of complement in the pathophysiologic mechanisms underlying clinical manifestations of SLE.


2009 ◽  
Vol 46 (14) ◽  
pp. 2870
Author(s):  
Lone N. Troelsen ◽  
Peter Garred ◽  
Buris Christiansen ◽  
Christian Torp-Pedersen ◽  
Ib J. Christensen ◽  
...  

2012 ◽  
Vol 14 (5) ◽  
pp. R218 ◽  
Author(s):  
Aditya K Panda ◽  
Jyoti R Parida ◽  
Rina Tripathy ◽  
Sarit S Pattanaik ◽  
Balachandran Ravindran ◽  
...  

2005 ◽  
Vol 191 (10) ◽  
pp. 1697-1704 ◽  
Author(s):  
W. K. Eddie Ip ◽  
Kwok Hung Chan ◽  
Helen K. W. Law ◽  
Gloria H. W. Tso ◽  
Eric K. P. Kong ◽  
...  

Abstract Little is known about the innate immune response to severe acute respiratory syndrome (SARS) coronavirus (CoV) infection. Mannose-binding lectin (MBL), a key molecule in innate immunity, functions as an ante-antibody before the specific antibody response. Here, we describe a case-control study that included 569 patients with SARS and 1188 control subjects and used in vitro assays to investigate the role that MBL plays in SARS-CoV infection. The distribution of MBL gene polymorphisms was significantly different between patients with SARS and control subjects, with a higher frequency of haplotypes associated with low or deficient serum levels of MBL in patients with SARS than in control subjects. Serum levels of MBL were also significantly lower in patients with SARS than in control subjects. There was, however, no association between MBL genotypes, which are associated with low or deficient serum levels of MBL, and mortality related to SARS. MBL could bind SARS-CoV in a dose- and calcium-dependent and mannan-inhibitable fashion in vitro, suggesting that binding is through the carbohydrate recognition domains of MBL. Furthermore, deposition of complement C4 on SARS-CoV was enhanced by MBL. Inhibition of the infectivity of SARS-CoV by MBL in fetal rhesus kidney cells (FRhK-4) was also observed. These results suggest that MBL contributes to the first-line host defense against SARS-CoV and that MBL deficiency is a susceptibility factor for acquisition of SARS


2014 ◽  
Vol 24 (1) ◽  
pp. 123-125 ◽  
Author(s):  
Kaname Akamata ◽  
Yoshihide Asano ◽  
Naohiko Aozasa ◽  
Shinji Noda ◽  
Takashi Taniguchi ◽  
...  

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