Complement deficiency states and meningococcal disease

Abstract

Analysis of complement deficiency states has supported the role of complement in host defense and elucidated diseases associated with defective complement function. Although neisserial infection plays a prominent role in these deficiency states, examination of individuals with late complement component deficiency (LCCD) reveals a particular propensity for recurrent meningococcal disease and provides important clues to the role of complement in neisserial infections. In response to meningococcal disease, LCCD individuals produce significantly greater amounts of antilipooligosaccharide (LOS) antibody which can kill group B meningococcus in a complement-sufficient in vitro system. Further studies of antibody cross-reactivity to other meningococci has led to a clearer understanding of its epitopic specificity. Nevertheless, epidemiologic evidence is consistent with the relative absence of protective immunity in LCCD persons following an episode of infection and supported by quantitation of antibody to capsular polysaccharide. However, compared to anti-LOS antibodies, anticapsular antibodies can offer immune protection to LCCD individuals via complement-dependent opsonophagocytosis--the only form of complement-mediated killing available to these persons. Thus vaccination of LCCD persons with capsular antigens is considered an important means of protecting these high-risk individuals against meningococcal disease.

Background Paper for the update of meningococcal vaccination recommendations in Germany: use of the serogroup B vaccine in persons at increased risk for meningococcal disease

“…The authors attributed this to more rapid access to an infectious diseases specialist through regular care within the context of HIV disease. In contrast, in a laboratorybased surveillance study from South Africa HIV-infected individuals had an incase series, and was found to be negatively correlated with IMD incidence [78].…”

“…Case fatality, however, is markedly lower than in individuals without complement deficiencies, at below 3 % [74,77], possibly because fewer cell membrane components and toxins are released by the bacteria in the absence of the membrane-attack complex [74]. The first episode of IMD in individuals with terminal complement deficiencies frequently occurs in adolescence, markedly later than in persons with intact complement [8,9,78]. While some case series suggest that the rarer serogroups W and Y occur more commonly in IMD patients with late complement deficiencies [79][80][81], IMD patients with and without complement deficiencies had similar serogroup distributions in a Dutch study [82].…”

“…An increased risk for infections (approximately 20 % higher than the background risk) has also been described, especially with encapsulated bacterial pathogens (primarily Streptococcus pneumoniae, but in rare cases also N. meningitidis) [9,74,78,84,85].…”

Remitting fever of unknown origin in a 20‐year‐old man

“…The risk of Neisseria infection increases 1,000 -10,000-fold in patients with complement defects, and the rate of recurrence is 44% in the US population (25). However, the increased risk of meningococcal infection in these individuals is associated with a relatively low mortality.…”

“…The mortality rate of Neisseria infection is 1.5% in patients with complement defects but 19% in patients with a fully functional complement system. The inability to mount an efficient bacterial lysis may be the reason for a reduced endotoxin level in complement-deficient patients, which usually leads to less severe clinical disease, shock, disseminated coagulopathy, and other factors (25).…”