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      International Journal of COPD (submit here)

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      Mannose-binding lectin deficiency and acute exacerbations of chronic obstructive pulmonary disease

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          Abstract

          Background:

          Mannose-binding lectin is a collectin involved in host defense against infection. Whether mannose-binding lectin deficiency is associated with acute exacerbations of chronic obstructive pulmonary disease is debated.

          Methods:

          Participants in a study designed to determine if azithromycin taken daily for one year decreased acute exacerbations had serum mannose-binding lectin concentrations measured at the time of enrollment.

          Results:

          Samples were obtained from 1037 subjects (91%) in the trial. The prevalence of mannose-binding lectin deficiency ranged from 0.5% to 52.2%, depending on how deficiency was defined. No differences in the prevalence of deficiency were observed with respect to any demographic variable assessed, and no differences were observed in time to first exacerbation, rate of exacerbations, or percentage of subjects requiring hospitalization for exacerbations in those with deficiency versus those without, regardless of how deficiency was defined.

          Conclusion:

          In a large sample of subjects with chronic obstructive pulmonary disease selected for having an increased risk of experiencing an acute exacerbation of chronic obstructive pulmonary disease, only 1.9% had mannose-binding lectin concentrations below the normal range and we found no association between mannose-binding lectin concentrations and time to first acute exacerbation or frequency of acute exacerbations during one year of prospective follow-up.

          Most cited references46

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          A second serine protease associated with mannan-binding lectin that activates complement.

          The complement system comprises a complex array of enzymes and non-enzymatic proteins that is essential for the operation of the innate as well as the adaptive immune defence. The complement system can be activated in three ways: by the classical pathway which is initiated by antibody-antigen complexes, by the alternative pathway initiated by certain structures on microbial surfaces, and by an antibody-independent pathway that is initiated by the binding of mannan-binding lectin (MBL; first described as mannan-binding protein) to carbohydrates. MBL is structurally related to the complement C1 subcomponent, C1q, and seems to activate the complement system through an associated serine protease known as MASP (ref. 4) or p100 (ref. 5), which is similar to C1r and C1s of the classical pathway. MBL binds to specific carbohydrate structures found on the surface of a range of microorganisms, including bacteria, yeasts, parasitic protozoa and viruses, and exhibits antibacterial activity through killing mediated by the terminal, lytic complement components or by promoting phagocytosis. The level of MBL in plasma is genetically determined, and deficiency is associated with frequent infections in childhood, and possibly also in adults (for review, see ref. 6). We have now identified a new MBL-associated serine protease (MASP-2) which shows a striking homology with the previously reported MASP (MASP-1) and the two C1q-associated serine proteases C1r and C1s. Thus complement activation through MBL, like the classical pathway, involves two serine proteases and may antedate the development of the specific immune system of vertebrates.
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            Mannose-binding lectin binds to a range of clinically relevant microorganisms and promotes complement deposition.

            Mannose-binding lectin (MBL) is a collagenous serum lectin believed to be of importance in innate immunity. Genetically determined low levels of the protein are known to predispose to infections. In this study the binding of purified MBL to pathogens isolated from immunocompromised children was investigated by flow cytometry. Diverse Candida species, Aspergillus fumigatus, Staphylococcus aureus, and beta-hemolytic group A streptococci exhibited strong binding of MBL, whereas Escherichia coli, Klebsiella species, and Haemophilus influenzae type b were characterized by heterogeneous binding patterns. In contrast, beta-hemolytic group B streptococci, Streptococcus pneumoniae, and Staphylococcus epidermidis showed low levels of binding. Bound MBL was able to promote C4 deposition in a concentration-dependent manner. We conclude that MBL may be of importance in first-line immune defense against several important pathogens.
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              Acute respiratory tract infections and mannose-binding lectin insufficiency during early childhood.

              Hospital-based studies have found that increased susceptibility to certain infections is associated with low serum levels of mannose-binding lectin (MBL) due to MBL variant alleles. However, the contribution of MBL insufficiency to incidence of common childhood infections at a population level is unknown. To investigate the effect of MBL insufficiency on risk for acute respiratory tract infection (ARI) in unselected children younger than 2 years. Population-based, prospective, cohort study conducted in Sisimiut, Greenland. Two hundred fifty-two children younger than 2 years who were followed up weekly between August 1996 and August 1998 for morbidity surveillance. Risk of ARI, based on medical history and clinical examination, compared by MBL genotype, determined from blood samples based on presence of structural and promoter alleles. A 2.08-fold (95% confidence interval [CI], 1.41-3.06) increased relative risk (RR) of ARI was found in MBL-insufficient children (n = 13) compared with MBL-sufficient children (n = 239; P<.001). The risk association was largely restricted to children aged 6 to 17 months (RR, 2.92; 95% CI, 1.78-4.79) while less effect (RR, 1.47; 95% CI, 0.45-4.82) and no effect (RR, 1.00; 95% CI, 0.42-2.37) was shown among children aged 0 to 5 months and 18 to 23 months, respectively. These data suggest that genetic factors such as MBL insufficiency play an important role in host defense, particularly during the vulnerable period of childhood from age 6 through 17 months, when the adaptive immune system is immature.
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                Author and article information

                Journal
                Int J Chron Obstruct Pulmon Dis
                Int J Chron Obstruct Pulmon Dis
                International Journal of COPD
                International Journal of Chronic Obstructive Pulmonary Disease
                Dove Medical Press
                1176-9106
                1178-2005
                2012
                2012
                23 November 2012
                : 7
                : 767-777
                Affiliations
                [1 ]Medicine Service, Denver Health and Department of Medicine, University of Colorado Denver, Denver, CO
                [2 ]Division of Biostatistics, School of Public Health, University of Minnesota, Minneapolis, MN
                [3 ]Pulmonary and Critical Care Medicine, Department of Medicine, University of Michigan, Ann Arbor, MI
                [4 ]Pulmonary and Critical Care Medicine, VA Medical Center, Ann Arbor, MI
                [5 ]Pulmonary and Critical Care Medicine, Department of Medicine, and Cardiovascular Research Institute, University of California, San Francisco, CA, USA
                Author notes
                Correspondence: Richard K Albert, Email ralbert@ 123456dhha.org
                Article
                copd-7-767
                10.2147/COPD.S33714
                3514010
                23226013
                b64f5877-b258-4326-9ce6-eb77878609fa
                © 2012 Albert et al, publisher and licensee Dove Medical Press Ltd.

                This is an Open Access article which permits unrestricted noncommercial use, provided the original work is properly cited.

                History
                : 22 November 2012
                Categories
                Original Research

                Respiratory medicine
                acute exacerbations,mannose-binding lectin,copd
                Respiratory medicine
                acute exacerbations, mannose-binding lectin, copd

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