Complement Defects in Patients with Chronic Rhinosinusitis

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From: PLoS ONE(Vol. 7, Issue 11)
Publisher: Public Library of Science
Document Type: Article
Length: 4,950 words
Lexile Measure: 1440L

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Author(s): Maria Q. Gaunsbaek 1 , * , Bibi Lange 1 , Anette D. Kjeldsen 1 , Viggo Svane-Knudsen 1 , Karsten Skjoedt 2 , Maiken L. Henriksen 2 , Christian Nielsen 3 , Yaseelan Palarasah 2 , Soren Hansen 2

Introduction

Chronic rhinosinusitis (CRS) is a common disease with considerable impact on quality of life and airway morbidity. Phenotyping CRS is still an ongoing subject for discussion and CRS is difficult to diagnose due to the lack of available biomarkers. The causes of CRS are still largely unknown but may involve cilia dysfunction or polymorphism in genes involved in regulation of inflammatory responses [1], [2]. Common underlying disorders such as asthma, allergy and immunodeficiency have been associated with CRS [3]-[5]. In patients with cystic fibrosis the prevalence of CRS is close to 100%. Healthy carriers of a mutation otherwise associated with cystic fibrosis have also a significantly increased prevalence of CRS compared to the general population [6]. Numerous studies support a link between smoking and CRS and several studies describe biofilm formation on sinonasal mucosal surfaces as mediator of the inflammation in CRS [7], [8]. In a Danish study investigating risk factors, an increased CRS prevalence was correlated significantly with occupational exposure to inhaled particles [9]. The mechanisms that underlie inflammation in CRS have not yet been fully revealed.

The complement system is an important part of the innate immune system and helps to clear invading microorganisms. The complement system is activated by three pathways: the classical, the alternative and the lectin pathway. The classical pathway is activated by binding of C1q to antigen-antibody complexes. The lectin pathway is activated by binding of either Mannan-binding lectin (MBL) or Ficolins to microbial surfaces. The alternative pathway is spontaneously and continuously activated in the blood at a low rate by the hydrolysis of the thioester group within C3, but this activation pathway is controlled in the host by several regulatory molecules [10]-[12]. Recently, it was demonstrated that Collectin 11 (CL-11, alias CL-K1) also was associated with complement-activating proteases and may be yet an activator of the lectin pathway [13], [14]. The pathways converge into a common point, when C3 is cleaved into C3a and C3b. Deposition of C3b leads to opsonisation and potentially to formation of a membrane attack complex, C5b-C9, resulting in lysis of microorganisms. During activation, small chemotactic fragments, C5a and C3a, are released to attract and activate inflammatory cells at the site of infection. Albeit there is a large degree of redundancy among the three pathways, it is well known that deficiencies of the complement system can lead to increased susceptibility to infections and inflammatory diseases [11], [15], [16]. Many studies have focused on serious infections and rheumatologic disorders [17]-[20]. Other studies have shown an up-regulation of complement components in human sinonasal tissue of CRS patients [21], [22], indicating that the complement system also plays a role in the sinonasal inflammatory response. Only few studies have focused on the association between complement deficiencies and CRS. Chinese CRS patients...

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Gale Document Number: GALE|A477091811