Complement factor 7 gene mutations in relation to meningococcal infection and clinical recurrence of meningococcal disease.

Abstract	Meningococcal disease is caused by Neisseria meningitidis which is associated with high morbidity and mortality. Recurrences of meningococcal infection have been observed in patients with terminal complement component defects, because of the inefficient formation of the lytic membrane attack complex (MAC), C5b-9. Complement component C7 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 patients were screened for aberrant C7 protein by isoelectric focusing (C7 IEF). These were compared with patients in whom recurrent meningococcal infection had resulted in the diagnosis of complete C7 absence (C7Q0). A higher proportion of C7 IEF variants were found in meningitis cases compared to controls (p=0.03). In contrast to C7Q0 patients, recurrent meningococcal infection was never observed in C7 IEF cases. Whereas C7Q0 sera were defective in meningococcal serogroup B and W135 killing assays, the sera of patients with C7 IEF 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 C76 and C78 IEF pattern and identified three novel C7 gene mutations in 13 C7Q0 patients. In conclusion, C7 IEF 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 meningococcal infection.
Authors	Taco W Kuijpers, Melanie Nguyen, Carla Th P Hopman, Ed Nieuwenhuys, Georg Dewald, Arjan C Lankester, Anja Roos, Arie van der Ende, Cees Fijen, Martin de Boer
Journal	Molecular immunology (Mol Immunol) Vol. 47 Issue 4 Pg. 671-7 (Jan 2010) ISSN: 1872-9142 [Electronic] England
PMID	19931914 (Publication Type: Journal Article)
Copyright	Copyright 2010 Elsevier Ltd. All rights reserved.
Chemical References	Complement C7
Topics	Adolescent Adult Case-Control Studies Child Child, Preschool Complement C7 (chemistry, genetics, immunology) Cytotoxicity, Immunologic Female Humans Immunoblotting Isoelectric Focusing Male Meningococcal Infections (genetics, immunology, prevention & control) Mutation (genetics) Neisseria meningitidis (classification, immunology) Pedigree Phenotype Recurrence Serotyping Young Adult

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