High prevalence of complement component C6 deficiency among African-Americans in the South-eastern USA

Abstract

SUMMARYComplement component C6 is a part of the membrane attack complex that forms a pore-like structure in cell membranes following complement activation. De®ciency of terminal complement components including C6 predisposes individuals to infection with Neisseriae. Using polymerase chain reaction/ single-strand conformation polymorphism analysis followed by DNA sequencing, we screened genomic DNA from 200 randomly chosen blacks and an equal number from whites for three loss-of-function C6 mutations. Ten blacks and two whites were found to be heterozygous for one of the mutations. Two of the mutations, 1195delC and 1936delG, were found exclusively in black individuals. A third previously undescribed mutation, 878delA, was found at equal frequency among the two groups. The difference between the two groups was signi®cant (P 0´027), indicating that C6 de®ciency due to these three mutations is more common among blacks than whites in the local area, principally Jefferson County, Alabama. In addition, three previously undescribed point mutations, two of which result in amino acid substitutions, were identi®ed within exon 6. A review of the county health department records over the past 6 years revealed a higher incidence of meningococcal meningitis in blacks due to serogroups Y and W-135 which paralleled the difference in the estimated prevalence of C6 de®ciency. Among black residents of the county (n 235 598) there were 15 cases of meningitis due to these two serogroups, compared with two cases in the white population (n 422 604) (P 0´002). We conclude that C6 de®ciency is more common among blacks than whites in the south-eastern United States, with a frequency approaching 1 in 1600 black individuals.

Digestive vacuole of Plasmodium falciparum released during erythrocyte rupture dually activates complement and coagulation

“…Only 2 speculations for this have been advanced at this point: (1) the dynamics of DV release and removal may be important and the efficacy of phagocyte uptake of DVs is possibly subject to wide interindividual variations, and (2) genetic deficiencies in late complement components occur worldwide with varying and sometimes surprisingly high frequency. 51 Heterozygotes are not prone to suffer from bacterial infections because serum complement activity is only lowered, but perhaps these individuals are protected against the effects of complement overactivation that lead to severe malaria.…”

The C5 Convertase Is Not Required for Activation of the Terminal Complement Pathway in Murine Experimental Cerebral Malaria

“…This raises the possibility that selective pressure on terminal pathway genes (C6 through C9) could be a mechanism for surviving malaria and/or cerebral malaria. C6 and C9 deficiencies are common in humans (37), but C6 deficiency is highly prevalent in African Americans in the southeastern United States, with a frequency of almost 1 in 1600 (38). These individuals likely originated in West Africa and moved through the Caribbean and then into the southeastern United States (39) based on the tracking of two loss-of-function mutations in C6.…”

Déficit en fraction terminale du complément révélé dès le premier épisode d’infection invasive à méningocoque

“…Certains sérogroupes du méningo-coque (Y, W, X) sont plus fréquemment observés chez les patients déficitaires en protéines du complément avec notamment une incidence d'environ 35 % de sérogroupe Y contre 5 % chez les patients non déficitaires [2]. Pour certains auteurs, une première IIM à ces sérogroupes rares (Y, W, X, E ou des souches non-capsulées) nécessiterait une exploration du complément [4,9,16]. En France, le typage génétique systé-matique par multi locus sequence typing (MLST) de toutes les souches de méningocoque adressées au CNRM a permis d'identifier des souches dites « hyper-invasives » appartenant à des complexes clonaux particuliers (ST-11, ST-41/44, ST-32, ST-8, ST-269) responsables de la majorité (plus de 85 %) des cas d'IIM chez le sujet immunocompétent [17,18].…”