Chapter 4 - Relevance of the lectin pathway of complement in rheumatic diseases

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Abstract

Due to its importance both in the clearance of pathogens that contribute as rheumatic etiological agents and in the disposal of apoptotic bodies and potential autoimmune initiators, deficiencies of the components of the lectin pathway of complement have been found to increase susceptibility and modulate the severity of most rheumatic disorders. This chapter introduces the general aspects of the structure, function, and genetics of lectin pathway components and summarizes current knowledge of

Complement Activation and Regulation System

The innate immune system, the first line of host defense, consists of several humoral and cellular mechanisms that recognize potential pathogens within minutes or hours of entry. The activation of the innate immunity is driven by the recognition of specific patterns present on the surface of microbes and altered self-constituents. This recognition is based on preformed elements, a feature that enables activation of humoral and cellular elements few minutes after infection. Following this rapid

The Lectin Pathway and Rheumatological Disorders

MBL as well as l and h-FCNs have been found to mediate the clearance of apoptotic cells [49], [135], [136], [156]. Deficiencies of these molecules are thus expected to increase the susceptibility to autoimmune manifestations such as those implicated in several rheumatological conditions, beyond increasing the susceptibility to infectious etiological agents that may also be involved in the disease process (Fig. 13). Alternatively, an increased concentration of lectin pathway components could

Conclusions

In this chapter, we have reviewed the diverse functional roles and common genetic polymorphisms of lectin pathway components and how they influence rheumatologic diseases. Initially, studies on the deficiency of these components focused on disease susceptibility, but recently it was recognized that they play a significant role in the modulation of inflammatory response, and as such may influence disease severity. This modulation is complex and differs between rheumatologic diseases and

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      While on the one hand its activation could contribute to tissue damage and consequently to disease severity, on the other hand, deficiencies of complement proteins may enhance autoimmunity (Ballanti et al., 2013). Considering that, the lectin pathway is involved in the clearance of pathogens and apoptotic bodies that may act as potential autoimmune initiators, deficiencies of components of these pathway could enhance susceptibility and severity of some rheumatic disorders such as RA (Boldt et al., 2012). However, our meta-analysis showed no association between low producing MBL2 genotypes and susceptibility to RA, indicating that variation on MBL levels inferred by MBL2 polymorphisms may not be a risk factor for RA development.

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    Both the authors contributed equally to this work.

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