Autoantibody stabilization of the classical pathway C3 convertase leading to C3 deficiency and Neisserial sepsis: C4 nephritic factor revisited. Clin Immunol 2012 Dec;145(3):241-50
Date
11/03/2012Pubmed ID
23117396Pubmed Central ID
PMC3501611DOI
10.1016/j.clim.2012.09.007Scopus ID
2-s2.0-84867898001 (requires institutional sign-in at Scopus site) 32 CitationsAbstract
C3 deficiency is a rare disorder that leads to recurrent pyogenic infections. Here we describe a previously healthy 18 y/o Caucasian male with severe meningococcal disease. Total hemolytic activity was zero secondary to an undetectable C3. The C3 gene was normal by sequencing. Mixing the patient's serum with normal human serum led to C3 consumption. An IgG autoantibody in the patient's serum was identified that stabilized the classical pathway C3 and C5 convertases, thus preventing decay of these enzyme complexes. This autoantibody is an example of a C4 nephritic factor, with an additional feature of stabilizing the C5 convertase. Previous patients with C4 nephritic factor had membranoproliferative glomerulonephritis. Two years after presentation, this patient's C3 remains undetectable with no evidence of renal disease. We revisit the role of autoantibodies to classical pathway convertases in disease, review the literature on C4-NeF and comment on its detection in the clinical laboratory.
Author List
Miller EC, Chase NM, Densen P, Hintermeyer MK, Casper JT, Atkinson JPAuthor
James Casper MD Emeritus Professor in the Pediatrics department at Medical College of WisconsinMESH terms used to index this publication - Major topics in bold
AdolescentAutoantibodies
Complement C3
Complement C3 Convertase, Classical Pathway
Complement C5 Convertase, Classical Pathway
Complement System Proteins
Enzyme Stability
Humans
Immunoglobulin G
Male
Meningitis, Meningococcal
Meningococcal Infections
Models, Immunological
Sepsis
Sequence Analysis, DNA
