Medizinische Universität Graz Austria/Österreich - Forschungsportal - Medical University of Graz
Gewählte Publikation:
SHR Neuro Krebs Kardio Lipid Stoffw Microb
Strobel, S; Hoyer, PF; Mache, CJ; Sulyok, E; Liu, WS; Richter, H; Oppermann, M; Zipfel, PF; Józsi, M.
Functional analyses indicate a pathogenic role of factor H autoantibodies in atypical haemolytic uraemic syndrome.
Nephrol Dial Transplant. 2010; 25(1): 136-144.
Doi: 10.1093/ndt/gfp388
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- Co-Autor*innen der Med Uni Graz
- Mache Christoph
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- Abstract:
- Methods. CFH autoantibodies were identified and antibody levels were analysed in three aHUS patients during the disease course by the ELISA method. Epitope mapping was performed using recombinant factor H fragments and domain-mapped monoclonal antibodies. The effect of the antibodies on cell-protective activity of CFH was measured by haemolytic assays. CFH:autoantibody complexes were analysed by ELISA. Results. All three autoantibodies bound to the C-terminal domain of CFH, which is essential for CFH binding to cell surfaces. In patient 1, plasma exchanges and immune adsorption temporarily reduced the autoantibody titre and led to temporary clinical improvement. In patient 2, plasma exchanges and long-term immunosuppression strongly reduced the CFH autoantibody level, and induced a stable remission of aHUS. Patient 3 had lower autoantibody levels that decreased during the follow-up and is in good clinical condition. The patients' plasma samples caused enhanced lysis of sheep erythrocytes, and the degree of lysis correlated with the CFH autoantibody titre and the amount of CFH:autoantibody complexes. An addition of purified CFH to aHUS plasma or removal of IgG inhibited the haemolytic activity. Conclusion. These results support a direct role of the autoantibodies in aHUS pathology by inhibiting the regulatory function of CFH at cell surfaces and suggest that reduction of the autoantibody titre is beneficial for the patients.
- Find related publications in this database (using NLM MeSH Indexing)
- Autoantibodies - blood
- Autoimmune Diseases - blood
- Child -
- Complement Factor H - immunology
- Disease Progression -
- Female -
- Hemolytic-Uremic Syndrome - blood
- Humans -
- Immunoglobulin G - blood
- Male -
- Find related publications in this database (Keywords)
- autoantibody
- complement
- factor H
- haemolytic uraemic syndrome