Complement factor 7 gene mutations in relation to XXXX and clinical recurrence of @entity7135 .

@entity1 @entity693 @entity465 @entity7135 @entity2483 @entity3631
@entity7135 is caused by @entity3631 which is associated with high morbidity and mortality. Recurrences of @entity7135 have been observed in @entity1 with @entity465 , because of the inefficient formation of the lytic membrane attack complex (MAC), C5b-9. @entity2483 is one of the five plasma proteins to form the MAC. The gene C7 may carry mutations that cause functional abnormalities or the mere absence of the C7 protein. More than 200 @entity1 were screened for aberrant @entity2483 ( @entity2483 ). These were compared with @entity1 in whom recurrent @entity7135 had resulted in the diagnosis of complete C7 absence (C7Q0). A higher proportion of @entity2483 variants were found in @entity693 cases compared to controls (p=0.03). In contrast to C7Q0 @entity1 , recurrent @entity7135 was never observed in @entity2483 cases. Whereas C7Q0 sera were defective in meningococcal serogroup B and W135 killing assays, the sera of @entity1 with @entity2483 variants were only defective in complement-mediated killing when classical pathway activation by (endogenous) anti-meningococcal antibodies was blocked. Upon sequence analysis we characterized the genetic background of the C7*6 and C7*8 IEF pattern and identified three novel C7 gene mutations in 13 C7Q0 @entity1 . In conclusion, @entity2483 variants can determine meningococcal killing in the early stage of infection when antibody-independent killing prevails. The results endorse the lack of clinical recurrences once antibodies are present, whereas in C7Q0 patients the anti-meningococcal antibodies may not suffice to protect from recurrent @entity7135 .
