Deficiency of the eighth component of complement associated with recurrent meningococcal meningitis: case report and literature review

Rosa, Daniela Rosa da; Pasqualotto, Alessandro C.; Quadros, Maurício de; Prezzi, Sergio Henrique

doi:10.1590/s1413-86702004000400010

Cited by 8 publications

(3 citation statements)

References 13 publications

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“…While people with reduced levels of C3 or C4 are at increased risk [13], the most striking association is among individuals who lack components of the MAC; this association has been described in numerous family studies [17,18]. Affected individuals have an increased lifetime risk of meningococcal disease of 1000-10 000-fold compared with the general population, and can present with multiple attacks [19].…”

Section: Genetics Of Host Susceptibility To Meningococcal Infectionmentioning

confidence: 96%

Interactions between Neisseria meningitidis and the complement system

Schneider

Exley

Ram

et al. 2007

Trends in Microbiology

122

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Section: Genetics Of Host Susceptibility To Meningococcal Infectionmentioning

confidence: 96%

Interactions between Neisseria meningitidis and the complement system

Schneider

Exley

Ram

et al. 2007

Trends in Microbiology

122

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“…Complement-mediated opsonophagocytosis and bacteriolysis is a major host defense against N. meningitidis. Patients deficient in complement components, especially C5 to C9, are susceptible to meningococcal disease (28). Several mechanisms are used by N. meningitidis to evade killing by human complement, including the prevention of MAC insertion into the bacterial membrane and the recruitment of negative complement regulators (17,32).…”

Section: Discussionmentioning

confidence: 99%

“…NhhA contributes to serum resistance of N. meningitidis and protects bacteria from MAC deposition. The complement system is of central importance in the host innate immune defense against meningococcal proliferation in the circulation (25,28). N. meningitidis has developed various mechanisms to evade complement attack and is therefore inherently more resistant to complement-mediated killing than other gram-negative pathogens (10,13,17,32).…”

Section: Vol 76 2008mentioning

confidence: 99%

Meningococcal Outer Membrane Protein NhhA Is Essential for Colonization and Disease by Preventing Phagocytosis and Complement Attack

et al. 2008

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Neisseria meningitidis is a leading cause of meningitis and septicemia worldwide, with a rapid onset of disease and a high morbidity and mortality. NhhA is a meningococcal outer membrane protein included in the family of trimeric autotransporter adhesins. The protein binds to the extracellular matrix proteins heparan sulfate and laminin and facilitates attachment to host epithelial cells. In this study, we show that NhhA is essential for bacterial colonization of the nasopharyngeal mucosa in a murine model of meningococcal disease. Successful colonization depends on bacterial attachment but also to the capacity to overcome innate host immune responses. We found that NhhA protected bacteria from phagocytosis, which is important for the mucosal survival of bacteria. In addition, NhhA mediated extensive serum resistance that increased bacterial survival in blood and promoted lethal sepsis. The presence of NhhA protected bacteria from complement-mediated killing by preventing the deposition of the membrane attack complex. Taken together, the results of this work reveal that NhhA inhibits phagocytosis and protects bacteria against complement-mediated killing, which enhances both nasal colonization and the development of sepsis in vivo.

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Complement: Deficiency Diseases

Skattum

Truedsson

2015

Encyclopedia of Life Sciences

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The complement system is crucial for defence against pathogens, removal of unwanted materials such as dying cells or immune complexes as well as for development of adaptive immune responses. Genetically determined deficiencies of components of the complement system are usually relatively rare, but they result in many severe diseases such as an increased susceptibility to recurrent, severe bacterial infections, autoimmune disorders (systemic lupus erythematosus), glomerulonephritis including dense deposit disease and C3 glomerulonephritis, paroxysmal nocturnal haemoglobinuria or angioedema. In addition, mutations and polymorphisms in complement proteins, particularly complement inhibitors, have been associated with atypical haemolytic uremic syndrome and age‐related macular degeneration. The elucidation of the pathophysiological basis for the different clinical presentations of complement‐deficient individuals has contributed to a better understanding of the physiological role of complement in normal individuals as well as to the development of emerging therapies. Key Concepts The majority of complement deficiencies are rare but cause severe diseases. Deficiencies of the components of the classical pathway (C1q/r/s, C4 and C2) predispose to bacterial infections and systemic lupus erythematosus. The majority of complement deficiencies predispose to infections either with Neisseria species (deficiency of factor D, factor B, properdin, C5, C6, C7, C8 and C9) or with other encapsulated bacteria (C1q/r/s, mannose‐binding lectin, C2, C4, C3 and factor I). Mutations in C1q/r/s, C2, C4, C3, factor I and factor H can cause glomerulonephritis. Paroxysmal nocturnal haemoglobinuria is caused by deficiency of complement inhibitors CD55 and CD59. Hereditary angioedema is found in patients with low C1‐inhibitor level or dysfunctional C1‐inhibitor. Atypical haemolytic uremic syndrome is mainly associated with mutations and polymorphisms in complement inhibitors. Age‐related macular degeneration is associated with polymorphisms in complement inhibitor factor H.

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Deficiency of the eighth component of complement associated with recurrent meningococcal meningitis: case report and literature review

Cited by 8 publications

References 13 publications

Interactions between Neisseria meningitidis and the complement system

Interactions between Neisseria meningitidis and the complement system

Meningococcal Outer Membrane Protein NhhA Is Essential for Colonization and Disease by Preventing Phagocytosis and Complement Attack

Complement: Deficiency Diseases

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