Predictors of Chronic Obstructive Pulmonary Disease Exacerbations

Takeo Ishii; Kozui Kida

Disclosures

Curr Opin Pulm Med. 2014;20(2):138-145. 

In This Article

New Viewpoints From a SIGLEC-14 Study: Lectins and Proteins Related to Glycosylation

As exacerbations are mainly elicited by a viral or bacterial infection, we could speculate that genetic variations of pattern recognition molecules, including Toll-like receptors, NOD-like receptors, are associated with a frequent-exacerbation phenotype. Mannnose-binding lectin is a kind of collectin that belongs to Ca2+-dependent lectins and is a soluble pattern recognition receptor. Collectins have critical roles in innate immunity and also include surfactant A and D. As genetic variations of surfactant protein D are associated with emphysema in white and Japanese populations,[33,34] as well as with COPD progression,[35] their relation to exacerbation is also anticipated. Siglec-8 is an inhibitory member of the Siglec family of lectins expressed on eosinophils and mast cells, and its genetic variation is associated with bronchial asthma.[36] Eosinophilic exacerbation was observed in COPD,[37,38] and evidence of an allergic phenotype was associated with the risk of COPD exacerbations.[39] Thus, not only Siglec-14 but also other Siglecs including Siglec-8 have possible roles in the pathogenesis of various exacerbations types, that is, bacterial, allergic, and possibly viral. Genes for most of these Siglecs are clustered on chromosome 19q13.3–4,[40] and this region was shown to be relatively adjacent to a susceptibility locus for early-onset COPD by a linkage analysis[41] and also for COPD by a genome-wide association study, which had a larger population.[42] Siglecs could also have critical roles in COPD pathogenesis through modification of exacerbation susceptibility.

Siglecs are thought to have roles in recognizing 'self' by using sialic acids that are expressed on host cell surfaces .[28] However, sialic acid-binding viruses such as influenza virus utilize sialic acids on human cell surfaces to infect these cells.[32] Therefore, proteins related to glycosylation might be also good candidates for a pathogenesis investigation. Heterozygous Fut8 (α1,6-fucosyltransferase) knock-out mice exhibited an emphysema-prone phenotype;[43] also as a genetic variation that caused an amino-acid change in FUT8 was associated with emphysema in humans,[44] and patients with lower serum Fut8 activity experienced more frequent exacerbations.[45] Proteins related to glycosylation such as Fut8 might have some roles in exacerbation susceptibility.

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