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10.1038/ncomms8375 http://scihub22266oqcxt.onion/10.1038/ncomms8375 C4477037!4477037!26077231     free     free     free Deprecated: Implicit conversion from float 233.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 233.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 233.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 233.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 233.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534       Nat+Commun 2015 ; 6 (ä): ä Nephropedia Template TP {{tp|p=26077231|t=2015. Neutralization and clearance of GM-CSF by autoantibodies in pulmonary alveolar proteinosis |pdf=|usr=}}{{26077231}} gab.com Text Neutralization and clearance of GM-CSF by autoantibodies in pulmonary alveolar proteinosis JO: Nat Commun http://www.kidney.de/pget.php?&tw=1&pmid=26077231 #FOAvip Pulmonary alveolar proteinosis (PAP) is a severe autoimmune disease caused by autoantibodies that neutralize GM-CSF resulting in impaired function of alveolar macrophages. In this study, we characterize 21 GM-CSF autoantibodies from PAP patients and find that somatic mutations critically determine their specificity for the self-antigen. Individual antibodies only partially neutralize GM-CSF activity using an in vitro bioassay, depending on the experimental conditions, while, when injected in mice together with human GM-CSF, they lead to the accumulation of a large pool of circulating GM-CSF that remains partially bioavailable. In contrast, a combination of three non-cross-competing antibodies completely neutralizes GM-CSF activity in vitro by sequestering the cytokine in high-molecular-weight complexes, and in vivo promotes the rapid degradation of GM-CSF-containing immune complexes in an Fc-dependent manner. Taken together, these findings provide a plausible explanation for the severe phenotype of PAP patients and for the safety of treatments based on single anti-GM-CSF monoclonal antibodies. Twit Text FOAVip Neutralization and clearance of GM-CSF by autoantibodies in pulmonary alveolar proteinosis ????Nat Commun http://www.kidney.de/pget.php?&tw=1&pmid=26077231 #FOAvip Twit Text # Free Paper on # # # # # LINK http://www.kidney.de/pget.php?&tw=1&pmid=26077231 #FOAvip English Wikipedia <ref>{{Cite pmid|26077231}}</ref> Neutralization and clearance of GM-CSF by autoantibodies in pulmonary alveolar proteinosis #MMPMID26077231 Piccoli L; Campo I; Fregni CS; Rodriguez BMF; Minola A; Sallusto F; Luisetti M; Corti D; Lanzavecchia A Nat Commun 2015[]; 6 (ä): ä PMID26077231show ga Pulmonary alveolar proteinosis (PAP) is a severe autoimmune disease caused by autoantibodies that neutralize GM-CSF resulting in impaired function of alveolar macrophages. In this study, we characterize 21 GM-CSF autoantibodies from PAP patients and find that somatic mutations critically determine their specificity for the self-antigen. Individual antibodies only partially neutralize GM-CSF activity using an in vitro bioassay, depending on the experimental conditions, while, when injected in mice together with human GM-CSF, they lead to the accumulation of a large pool of circulating GM-CSF that remains partially bioavailable. In contrast, a combination of three non-cross-competing antibodies completely neutralizes GM-CSF activity in vitro by sequestering the cytokine in high-molecular-weight complexes, and in vivo promotes the rapid degradation of GM-CSF-containing immune complexes in an Fc-dependent manner. Taken together, these findings provide a plausible explanation for the severe phenotype of PAP patients and for the safety of treatments based on single anti-GM-CSF monoclonal antibodies. äNeutralization and clearance of GM-CSF by autoantibodies in pulmonary (epmc).pdf DeepDyve Pubget Overpricing