Complement deficiency and disease: An update

Sjöholm, Anders G.; Jönsson, Göran; Braconier, Jean Henrik; Sturfelt, Gunnar; Truedsson, Lennart

doi:10.1016/j.molimm.2005.06.025

Cited by 127 publications

(99 citation statements)

References 58 publications

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“…The contribution of the complement system to host defense against infections has been confirmed by an increased susceptibility of complement-deficient individuals to recurrent pyogenic infections. 41 For reasons that are not yet completely understood, this increased susceptibility is restricted to a limited number of bacteria. For example, deficiencies in late complement components (C5 to C9) and properdin are associated with recurrent infections caused by Neisseria meningitides and Neisseria gonorrhoeae.…”

Section: "Waste Disposal"mentioning

confidence: 99%

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The Role of Complement in Inflammatory Diseases From Behind the Scenes into the Spotlight

Markiewski

Lambris

2007

The American Journal of Pathology

599

575

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Our understanding of the biology of the complement system has undergone a drastic metamorphosis since its original discovery. This system, which was traditionally primarily described as a "complement" to humoral immunity, is now perceived as a central constituent of innate immunity, defending the host against pathogens, coordinating various events during inflammation, and bridging innate and adaptive immune responses. Complement is an assembly of proteins found in the blood and body fluids and on cell surfaces. Soluble complement components form the proteolytic cascade, whose activation leads to the generation of complement effectors that target various cells involved in the immune response. Membrane-bound receptors and regulators transmit signals from complement effectors to target cells and limit complement activation to the surfaces of pathogens and damaged or activated host cells. The multiple interconnections among complement proteins, immune cells, and mediators provide an excellent mechanism to protect the organism against infections and support the repair of damaged tissues. However, disturbances in this "defense machinery" contribute to the pathogenesis of various diseases. The role of complement in various inflammatory disorders is multifaceted; for example, the activation of complement can significantly contribute to inflammation-mediated tissue damage, whereas inherited or acquired complement deficiencies highly favor the development of autoimmunity.

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Section: "Waste Disposal"mentioning

confidence: 99%

“…An increased frequency of bacterial infections is also characteristic of deficiencies in classical pathway proteins and C3. 41 Despite the protective role of complement against microbial invasion, associations of complement with an inflammatory network can have pathogenic consequences when certain regulatory mechanisms fail.…”

Section: "Waste Disposal"mentioning

confidence: 99%

The Role of Complement in Inflammatory Diseases From Behind the Scenes into the Spotlight

Markiewski

Lambris

2007

The American Journal of Pathology

599

575

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“…Many of these individuals (>60%) do not suffer from any apparent disease, probably due to the compensatory involvement of factor B in the activation of the complement via C2 bypass mechanism (Laich and Sim, 2001). Almost 40% of individuals with C2 deficiency develop systemic autoimmune disease (Agnello et al, 1972;Day et al, 1973;Sjoholm et al, 2006). For instance, systemic lupus erythematosis (SLE) is a disease that presents with facial erythema and oral or nasopharyngeal ulceration.…”

Section: Early Components Of the Classical And Alternative Pathwaysmentioning

confidence: 99%

“…Deficiency of other genes encoding alternative pathway components, such as properdin and factor D, demonstrated the importance of this pathway in battling neisserial (meningococcal) infections (Sjoholm et al, 2002(Sjoholm et al, , 2006. Complete C3 deficiency caused serious infections in the 27 described cases, suggesting that this component is crucial for complement functional interplay with innate immunity.…”

Section: Early Components Of the Classical And Alternative Pathwaysmentioning

confidence: 99%

Complement genetics, deficiencies, and disease associations

Mayilyan

2012

Protein Cell

149

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The complement system is a key component of innate immunity. More than 45 genes encoding the proteins of complement components or their isotypes and subunits, receptors, and regulators have been discovered. These genes are distributed throughout different chromosomes, with 19 genes comprising three significant complement gene clusters in the human genome. Genetic deficiency of any early component of the classical pathway (C1q, C1r/s, C2, C4, and C3) is associated with autoimmune diseases due to the failure of clearance of immune complexes (IC) and apoptotic materials, and the impairment of normal humoral response. Deficiencies of mannan-binding lectin (MBL) and the early components of the alternative (factor D, properdin) and terminal pathways (from C3 onward components: C5, C6, C7, C8, C9) increase susceptibility to infections and their recurrence. While the association of MBL deficiency with a number of autoimmune and infectious disorders has been well established, the effects of the deficiency of other lectin pathway components (ficolins, MASPs) have been less extensively investigated due to our incomplete knowledge of the genetic background of such deficiencies and the functional activity of those components. For complement regulators and receptors, the consequences of their genetic deficiency vary depending on their specific involvement in the regulatory or signalling steps within the complement cascade and beyond. This article reviews current knowledge and concepts about the genetic load of complement component deficiencies and their association with diseases. An integrative presentation of genetic data with the latest updates provides a background to further investigations of the disease association investigations of the complement system from the perspective of systems biology and systems genetics.

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“…In addition, several groups have reported defective processing, and FcR-dependent clearance, of ICs and apoptotic cells in lupus patients [116][117][118]. Further indications of deficient removal of apoptotic material in SLE patients include the associations between relative or absolute deficiencies of certain components of the classical complement pathway (C1q, C1r, C1s, C4 or C2) and the occurrence of SLE [119,120].…”

Section: Sle and The Waste Disposal Hypothesismentioning

confidence: 99%

Pathogenic implications for autoantibodies against C-reactive protein and other acute phase proteins

Sjöwall

Wetterö

2007

Clinica Chimica Acta

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Systemic lupus erythematosus (SLE) is a systemic rheumatic disease characterized clinically by multiorgan involvement and serologically by the occurrence of antinuclear antibodies. SLE patients may present with multiple autoantibodies to cytoplasmic and cell surface antigens as well as to circulating plasma proteins. Another feature of SLE is that serum levels of C-reactive protein (CRP) often remain low despite high disease activity and despite high levels of other acute phase proteins and interleukin-6, i.e. the main CRP inducing cytokine. Apart from its important role as a laboratory marker of inflammation, CRP attracts increasing interest due to its many intriguing biological functions, one of which is a role as an opsonin contributing to the elimination of apoptotic cell debris, e.g. nucleosomes, thereby preventing immunization against autoantigens. Recently, autoantibodies against CRP and other acute phase proteins have been reported in certain rheumatic conditions, including SLE. Although the presence of anti-CRP autoantibodies does not explain the failed CRP response in SLE, antibodies directed against acute phase proteins have several implications of pathogenetic interest. This paper thus highlights the biological and clinical aspects of native and monomeric CRP and anti-CRP, as well as autoantibodies against mannose-binding lectin, serum amyloid A and serum amyloid P component. © 2006 Elsevier B.V. All rights reserved

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Complement deficiency and disease: An update

Cited by 127 publications

References 58 publications

The Role of Complement in Inflammatory Diseases From Behind the Scenes into the Spotlight

The Role of Complement in Inflammatory Diseases From Behind the Scenes into the Spotlight

Complement genetics, deficiencies, and disease associations

Pathogenic implications for autoantibodies against C-reactive protein and other acute phase proteins

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