Chapter 4 - Relevance of the lectin pathway of complement in rheumatic diseases
Section snippets
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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Cited by (21)
The role of the lectin pathway of the complement system in SARS-CoV-2 lung injury
2021, Translational ResearchCitation Excerpt :It is known that low concentrations of MBL are associated with recurrent infections in childhood, especially in combination with other states of immunodeficiency due to defects in microorganism opsonization.24 On the other hand, high concentrations of MBL can be harmful by facilitating infections by intracellular microorganisms and aggravating tissue damage by complement system activation.25-27 Although several clinical studies are associating COVID-19 with an increased risk of endotheliopathy and immunothrombosis,28,29 the pathophysiological mechanisms remain unclear.
Diagnostic potential of mannose binding lectin (MBL) gene polymorphism in rheumatoid arthritis patients
2021, Egyptian RheumatologistCitation Excerpt :The MBL activates the complement system and the pathophysiology of RA may include high-expression of MBL2. Lectin pathway has been implicated in many rheumatic diseases [12,13]. Immune complexes are recognized in RA by MBL, resulting in activation of the complement with a strong inflammatory response.
Mannose-binding lectin polymorphisms and rheumatoid arthritis: A short review and meta-analysis
2016, Molecular ImmunologyCitation Excerpt :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.
MBL-associated serine proteases (MASPs) and infectious diseases
2015, Molecular ImmunologyCitation Excerpt :Low MASP-2 levels, for example, were associated with an increased risk of severe chemotherapy-induced neutropenia in children with cancer (Schlapbach et al., 2007) and an acute decrease of MASP-2 levels in the early phase of septic shock correlated with in-hospital mortality (Charchaflieh et al., 2012). In contrast, increased levels of innate immunity proteins, which can in part be explained by polymorphisms in the corresponding genes, may contribute to exaggerated inflammatory responses (Boldt et al., 2012). High postoperative levels of MASP-2, for example, were associated with poor prognosis in colorectal cancer patients (Ytting et al., 2008).
Association of MASP2 polymorphisms and protein levels with rheumatic fever and rheumatic heart disease
2014, Human ImmunologyCitation Excerpt :Furthermore, the association between variants leading to low protein levels and protection against RF has been formerly found for MBL2 [35,36], but not for FCN2 [37]. The low basal concentrations of MBL and MASP-2 correspond to a lower capacity of complement activation, due to structural variants as p.52C, p.54D and p.57E in MBL2 and p.439H in MASP2 [30]. This reinforces our suggestion that complement activation through the lectin pathway promote the inflammatory response and subsequent tissue damage in rheumatic fever disease.
ANTIDIARRHOEAL EFFECT OF CASUARINA EQUISETIFOLIA ON EXPERIMENTAL ANIMALS
2022, International Journal of Pharmaceutical Sciences and Research
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Both the authors contributed equally to this work.