The complement system, a part of the innate immune system with several links to the adaptive immune system, plays an important role in the pathogenesis of many diseases. The purpose of this thesis was to document and clarify some of these mechanisms. The thesis is based on four papers (I-IV).
(I and II) Autoantibodies to the C3 cleaving enzyme complex of the alternative pathway, C3 nephritic factors (C3 NeF), cause partial C3 deficiency and are associated with increased susceptibility to bacterial infections. By analysis of samples from 20 patients with C3 NeF, it was confirmed that C3 NeF are of at least 2 types; one with fluid phase (C3 NeF type I) and one with solid phase (C3 NeF type II) activity. Different types of C3 NeF were associated with different serum complement profiles and symptoms. Only C3 NeF type II were found to be associated with circulating autoantibodies to the collagenous region of C1q (aC1qCLR). Defense against Neisseria meningitidis in 26 patients with low C3 concentrations due to C3 NeF was investigated. In patients and control children, homozygosity for the IgG1 and IgG3 IGHG alleles G1M*f and G3M*b was found to be associated with higher serum bactericidal activity (SBA) than was heterozygosity. IGHG alleles correlated to IgG subclass binding to live meningococci, while IgG subclass binding did not correlate to SBA. Thus, the mechanism of influence from IGHG genes on SBA is unclear. IGHG variants are important for immune defense against meningococci in states of deficient complement function. This relationship should be examined further.
(III) Serum levels of mannan-binding lectin (MBL) and antibodies to proteins from a potentially nephritogenic Streptococcus pyogenes strain (serotype M1 strain AP1) were investigated in 73 patients with acute poststreptococcal glomerulonephritis (AGN). Antibody responses to the serotype M1-related antigens M1, protein H and streptococcal inhibitor of complement were increased in patients compared to controls. The presence of MBL deficient individuals (serum concentration <0.1 mg/L) among AGN patients showed that the lectin pathway is not required in the pathogenesis of AGN.
(IV) Autoimmunity has been implied to participate in the pathogenesis of idiopathic sudden hearing loss (ISHL). Autoantibodies were analysed in sera from 92 patients with ISHL. The most frequently occurring antibody was aC1qCLR, detected in 12 patients (13 %), all with normal serum concentrations of C1q. In ISHL, aC1qCLR probably represents cross-reactivity between C1q and inner ear protein(s).
- Avdelningen för mikrobiologi, immunologi och glykobiologi - MIG
- Truedsson, Lennart, handledare
- Hellmark, Thomas, handledare
|Tilldelningsdatum||2008 maj 9|
|Status||Published - 2008|
Place: GK-salen, BMC, Sölvegatan 21, Lund
Name: Meri, Seppo
Title: MD, Professor
Affiliation: Haartmann Institute, University of Helsinki, Helsinki, Finland
- Immunologi inom det medicinska området
- Mikrobiologi inom det medicinska området