Meningococcal septicaemia in a C6-deficient patient and effects of plasma transfusion on lipopolysaccharide release

doi:10.1016/0140-6736(92)92561-S

The Lancet

Volume 340, Issue 8832, 5 December 1992, Pages 1379-1381

https://doi.org/10.1016/0140-6736(92)92561-S Get rights and content

Abstract

Patients whose blood is deficient in the terminal component of complement have an increased susceptibility to meningococcal infection. However, mortality from meningococcal infection is lower in these patients than in immunocompetent subjects. We studied a C6-deficient patient with meningococcal sepsis who received fresh frozen plasma (FFP). The patient's initial plasma endotoxin, C6, and terminal-complement-complex concentrations were low, but rose sharply after treatment with FFP. Samples of the patient's serum taken shortly after admission did not cause endotoxin release from Escherichia coli J5 in vitro, but endotoxin-releasing activity was restored in serum samples taken after infusion of FFP. It is possible that C6-deficient patients have reduced mortality from meningococcal infection because their serum cannot cause acute release of endotoxin from the invading organism and extensive tissue damage is thus avoided.

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Citation Excerpt :
MAC insertion into gram-negative membranes results in lipopolysaccharide (LPS; endotoxin) release (O’Hara et al., 2001; Tesh et al., 1986); the amount of complement activation correlates with endotoxin release and disease severity (Brandtzaeg et al., 1989). Conversely, lack of the ability to effectively form the MAC pore limits the amount of endotoxin released (Lehner et al., 1992) and consequently such individuals enjoy a lower mortality per meningococcal disease episode. Eculizumab use is also associated with a ∼2000-fold higher risk of invasive meningococcal infection; most reported cases were caused by unencapsulated (non-groupable) isolates (McNamara et al., 2017).
Pathogens that invade the human host are confronted by a multitude of defence mechanisms aimed at preventing colonization, dissemination and proliferation. The most frequent outcome of this interaction is microbial elimination, in which the complement system plays a major role. Complement, an essential feature of the innate immune machinery, rapidly identifies and marks pathogens for efficient removal. Consequently, this creates a selective pressure for microbes to evolve strategies to combat complement, permitting host colonization and access to resources. All successful pathogens have developed mechanisms to resist complement activity which are intimately aligned with their capacity to cause disease. In this review, we describe the successful methods various pathogens use to evade complement activation, shut down inflammatory signalling through complement, circumvent opsonisation and override terminal pathway lysis. This review summarizes how pathogens undermine innate immunity: ‘The Hijackers Guide to Complement’.
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SHORT REPORTSMeningococcal septicaemia in a C6-deficient patient and effects of plasma transfusion on lipopolysaccharide release

Abstract

Endotoxins and disease mechanisms

Ann Rev Med

Plasma endotoxin as a predictor of multiple organ failure and death in systemic meningococcal disease

J Infect Dis

Complement deficiency states and infection: epidemiology, pathogenesis and consequences of neisserial and other infections in an immune deficiency

Medicine (Baltimore)

Observations on the measurement and evaluation of endotoxaemia by a quantitative Limulus lysate microassay

J Infect Dis

SHORT REPORTS
Meningococcal septicaemia in a C6-deficient patient and effects of plasma transfusion on lipopolysaccharide release