Oppermann, Martin

[["dc.bibliographiccitation.firstpage","136"],["dc.bibliographiccitation.issue","1"],["dc.bibliographiccitation.journal","Nephrology Dialysis Transplantation"],["dc.bibliographiccitation.lastpage","144"],["dc.bibliographiccitation.volume","25"],["dc.contributor.author","Strobel, Stefanie"],["dc.contributor.author","Hoyer, Peter F."],["dc.contributor.author","Mache, Christoph J."],["dc.contributor.author","Sulyok, Endre"],["dc.contributor.author","Liu, Wei-shih"],["dc.contributor.author","Richter, Heiko"],["dc.contributor.author","Oppermann, Martin"],["dc.contributor.author","Zipfel, Peter F."],["dc.contributor.author","Jozsi, Mihaly"],["dc.date.accessioned","2018-11-07T08:48:11Z"],["dc.date.available","2018-11-07T08:48:11Z"],["dc.date.issued","2010"],["dc.description.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."],["dc.description.sponsorship","Deutsche Forschungsgemeinschaft; Kidneeds Foundation, Cedar Rapids, US"],["dc.identifier.doi","10.1093/ndt/gfp388"],["dc.identifier.isi","000273113100024"],["dc.identifier.pmid","19666655"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/21150"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.publisher","Oxford Univ Press"],["dc.relation.issn","0931-0509"],["dc.title","Functional analyses indicate a pathogenic role of factor H autoantibodies in atypical haemolytic uraemic syndrome"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.status","published"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","1516"],["dc.bibliographiccitation.issue","5"],["dc.bibliographiccitation.journal","Blood"],["dc.bibliographiccitation.lastpage","1518"],["dc.bibliographiccitation.volume","110"],["dc.contributor.author","Jozsi, Mihaly"],["dc.contributor.author","Strobel, Stefanie"],["dc.contributor.author","Dahse, Hans-Martin"],["dc.contributor.author","Liu, Wei-Shih"],["dc.contributor.author","Hoyer, Peter F."],["dc.contributor.author","Oppermann, Martin"],["dc.contributor.author","Skerka, Christine"],["dc.contributor.author","Zipfel, Peter F."],["dc.date.accessioned","2018-11-07T10:58:46Z"],["dc.date.available","2018-11-07T10:58:46Z"],["dc.date.issued","2007"],["dc.description.abstract","The atypical form of the kidney disease hemolytic uremic syndrome (aHUS) is associated with defective complement regulation. In addition to mutations in complement regulators, factor H (FH)specific autoantibodies have been reported for aHUS patients. The aim of the present study was to understand the role of these autoantibodies in aHUS. First, the binding sites of FH autoantibodies from 5 unrelated aHUS patients were mapped using recombinant FH fragments and competitor antibodies. For all 5 autoantibodies, the binding site was localized to the FH C-terminus. In a functional assay, isolated patient IgG inhibited FH binding to C3b. In addition, autoantibody positive patients' plasma caused enhanced hemolysis of sheep erythrocytes, which was reversed by adding FH in excess. These results suggest that aHUS associated FH autoantibodies mimic the effect of C-terminal FH mutations, as they inhibit the regulatory function of FH at cell surfaces by blocking its C-terminal recognition region."],["dc.identifier.doi","10.1182/blood-2007-02-071472"],["dc.identifier.isi","000249151800026"],["dc.identifier.pmid","17495132"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/50540"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.publisher","Amer Soc Hematology"],["dc.relation.issn","0006-4971"],["dc.title","Anti-factor H autoantibodies block C-terminal recognition function of factor H in hemolytic uremic syndrome"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.status","published"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.issue","16"],["dc.bibliographiccitation.journal","Molecular Immunology"],["dc.bibliographiccitation.volume","44"],["dc.contributor.author","Strobel, Stefanie"],["dc.contributor.author","Dahse, Hans-Martin"],["dc.contributor.author","Liu, Wei-shih"],["dc.contributor.author","Hoyer, Peter F."],["dc.contributor.author","Oppermann, Martin"],["dc.contributor.author","Terenyi, Nora"],["dc.contributor.author","Skerka, Christine"],["dc.contributor.author","Zipfel, Peter F."],["dc.contributor.author","Jozsi, Mihaly"],["dc.date.accessioned","2018-11-07T10:59:12Z"],["dc.date.available","2018-11-07T10:59:12Z"],["dc.date.issued","2007"],["dc.format.extent","3974"],["dc.identifier.doi","10.1016/j.molimm.2007.06.171"],["dc.identifier.isi","000249512100156"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/50647"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.publisher","Pergamon-elsevier Science Ltd"],["dc.publisher.place","Oxford"],["dc.relation.conference","11th European Meeting on Complement in Human Disease"],["dc.relation.eventlocation","Cardiff, WALES"],["dc.relation.issn","0161-5890"],["dc.title","Factor H-autoantibodies in atypical hemolytic uremic syndrome"],["dc.type","conference_abstract"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.status","published"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","2697"],["dc.bibliographiccitation.issue","10"],["dc.bibliographiccitation.journal","Molecular Immunology"],["dc.bibliographiccitation.lastpage","2706"],["dc.bibliographiccitation.volume","44"],["dc.contributor.author","Jozsi, Mihaly"],["dc.contributor.author","Oppermann, Martin"],["dc.contributor.author","Lambris, John D."],["dc.contributor.author","Zipfel, Peter F."],["dc.date.accessioned","2018-11-07T11:03:45Z"],["dc.date.available","2018-11-07T11:03:45Z"],["dc.date.issued","2007"],["dc.description.abstract","Complement is a powerful self-amplifying system of innate immune defense with the capacity to eliminate microbes directly. Factor H is a central regulator in plasma which protects host tissue from complement mediated damage. Here we characterize the relevance of surface attached factor H, and study the regulatory activity of factor H on endothelial cells. Although these cells expressed membrane bound regulators, cell bound factor H contributed substantially to complement regulatory activity at the cell surface. Blockade of the C-terminus of factor H with monoclonal antibodies inhibited cell binding of this soluble regulator and resulted in enhanced complement activation on the cells. In the absence of factor H, increased deposition and slower inactivation of C3b resulted in higher amount of membrane attack complexes on the cell surface. When the membrane regulators CD55 and CD59 were removed by enzymatic treatment, complement mediated cell lysis was enhanced in the absence of factor H. Importantly, inhibition of the C-terminus did not compromise the regulatory function of factor H in fluid phase. Altogether these data point to a highly relevant, yet so far underestimated role of factor H for complement control at cellular surfaces, and reveal a decisive role of the factor H C-terminus in host cell recognition and protection. (c) 2006 Elsevier Ltd. All rights reserved."],["dc.description.sponsorship","NIAID NIH HHS [AI 30040, N01AI30040, R01 AI030040, R01 AI030040-12]"],["dc.identifier.doi","10.1016/j.molimm.2006.12.001"],["dc.identifier.isi","000245681200022"],["dc.identifier.pmid","17208302"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/51684"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.publisher","Pergamon-elsevier Science Ltd"],["dc.publisher.place","Oxford"],["dc.relation.conference","10th Meeting on Complement in Human Disease"],["dc.relation.eventlocation","Heidelberg, GERMANY"],["dc.relation.issn","0161-5890"],["dc.title","The C-terminus of complement factor H is essential for host cell protection"],["dc.type","conference_paper"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.status","published"],["dspace.entity.type","Publication"]]