IgA nephropathy (IgAN) is the most common form of primary glomerulonephritis worldwide and a common cause of end-stage renal disease. Evaluation of a kidney biopsy is necessary for diagnosis, with routine immunofluorescence microscopy revealing dominant or co-dominant IgA immunodeposits usually with complement C3 and sometimes IgG and/or IgM. IgA nephropathy reduces life expectancy by more than 10 years and leads to kidney failure in 20-40% of patients within 20 years of diagnosis. There is accumulating clinical, genetic, and biochemical evidence that complement plays an important role in the pathogenesis of IgA nephropathy. The presence of C3 differentiates the diagnosis of IgA nephropathy from the subclinical deposition of glomerular IgA. Markers for the activation of the alternative and mannan-binding lectin (MBL) pathways in renal-biopsy specimens are associated with disease activity and portend a worse renal outcome. Complement proteins in the circulation have also been evaluated in IgA nephropathy and found to be of prognostic value. Recently, genetic studies have identified IgA nephropathy-associated loci. Within these loci are genes encoding products involved in complement regulation and interaction with immune complexes. Put together, these data identify the complement cascade as a rational treatment target for this chronic kidney disease. Recent case reports on the successful use of humanized anti-C5 monoclonal antibody eculizumab are consistent with this hypothesis, but a better understanding of the role of complement in IgA nephropathy is needed to guide future therapeutic interventions.
- MeSH
- chronická renální insuficience imunologie MeSH
- glomerulonefritida imunologie MeSH
- IgA nefropatie imunologie MeSH
- imunoglobulin A imunologie MeSH
- komplement C3 imunologie MeSH
- komplement C5 imunologie MeSH
- ledviny imunologie MeSH
- lidé MeSH
- zvířata MeSH
- Check Tag
- lidé MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- přehledy MeSH
- Research Support, N.I.H., Extramural MeSH
- MeSH
- aktivace komplementu MeSH
- dítě MeSH
- dospělí MeSH
- komplement 4 imunologie MeSH
- komplement C1 imunologie MeSH
- komplement C2 imunologie MeSH
- komplement C3 imunologie MeSH
- komplement C5 imunologie MeSH
- lidé středního věku MeSH
- lidé MeSH
- mladiství MeSH
- systémový lupus erythematodes imunologie MeSH
- Check Tag
- dítě MeSH
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mladiství MeSH
- mužské pohlaví MeSH
- ženské pohlaví MeSH
- MeSH
- fluorescenční protilátková technika využití MeSH
- imunomodulace * imunologie účinky léků MeSH
- komplement C3 imunologie účinky léků MeSH
- komplement C5 imunologie účinky léků MeSH
- komplement * imunologie účinky léků MeSH
- kultivační techniky metody využití MeSH
- lymfocyty imunologie účinky léků MeSH
- myši MeSH
- peritoneální makrofágy imunologie účinky léků MeSH
- receptory komplementu 3b imunologie účinky léků MeSH
- statistika jako téma MeSH
- tvorba protilátek * imunologie účinky léků MeSH
- zvířata MeSH
- Check Tag
- myši MeSH
- zvířata MeSH
