The role of complement in anti-bacterial defence

The complement system consists of several proteins present in human serum interacting among themselves and with the other compounds of the immune system in the host defence process. In particular, late complement component (C5, C6, C7 and C8) deficiencies (LCCD) are closely associated with Neisseria, mainly meningitidis, infections. The aim of our study was to verify this association in an Italian population by analyzing the complement profile in survivors of meningococcal meningitis. Ten out of the 59 (17%) subjects studied had homozygous LCCD (6 C8, 3 C7 and 1 C6). The meningococcal C strain was the most widely diffused (68%) and had infected all homozygous LCCD subjects. In addition meningococcal serogroup C seemed to be the least immunogenic when compared to serogroups A and B. These data confirm the close association between homozygous LCCD and meningococcal infections from common serogroups (A, B and C) in the Italian population. Anti-meningococcal vaccination is usually recommended for LCCD subjects because it increases, both quantitatively and qualitatively, the antibody component of anti-meningococcal immune defence. We therefore analyzed the levels of anti-polysaccharide (PS) A and PSC antibodies in the members of 4 families including normal subjects and subjects with homozygous and heterozygous C7, C8 or factor H defects, before and after vaccination with only PSA+C. Surprisingly, we found the highest levels of antibodies before vaccination in homozygous subjects, followed by heterozygous and normal controls, whereas, after vaccination, homozygous subjects showed the lowest increase of specific antibodies, indicating their relative incapacity to respond to meningococcal PS alone. In conclusion, we suggest that anti-meningococcal vaccination be given to LCCD patients, but only after specific anti-PSA and PSC antibodies are monitored.