Neutralization and clearance of GM-CSF by autoantibodies in pulmonary alveolar proteinosis
| LEADER | caa a22 4500 | ||
|---|---|---|---|
| 001 | 528785834 | ||
| 005 | 20190713030955.0 | ||
| 007 | cr unu---uuuuu | ||
| 008 | 180924s2015 xx s 000 0 eng | ||
| 024 | 7 | 0 | |a 10.3929/ethz-b-000102531 |2 doi |
| 024 | 7 | 0 | |a 10.1038/ncomms8375 |2 doi |
| 035 | |a (ETHRESEARCH)oai:www.research-collecti.ethz.ch:20.500.11850/102531 | ||
| 245 | 0 | 0 | |a Neutralization and clearance of GM-CSF by autoantibodies in pulmonary alveolar proteinosis |h [Elektronische Daten] |c [Luca Piccoli, Ilaria Campo, Chiara S. Fregni, Blanca M. Fernandez Rodriguez, Andrea Minola, Federica; id_orcid 0000-0003-3750-2752 Sallusto, Maurizio Luisetti, Davide Corti, Antonio Lanzavecchia] |
| 246 | 0 | |a Nat Commun | |
| 506 | |a Open access |2 ethresearch | ||
| 520 | 3 | |a 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. | |
| 540 | |a Creative Commons Attribution 4.0 International |u http://creativecommons.org/licenses/by/4.0 |2 ethresearch | ||
| 700 | 1 | |a Piccoli |D Luca |e joint author | |
| 700 | 1 | |a Campo |D Ilaria |e joint author | |
| 700 | 1 | |a Fregni |D Chiara S. |e joint author | |
| 700 | 1 | |a Fernandez Rodriguez |D Blanca M. |e joint author | |
| 700 | 1 | |a Minola |D Andrea |e joint author | |
| 700 | 1 | |a Sallusto |D Federica; id_orcid 0000-0003-3750-2752 |e joint author | |
| 700 | 1 | |a Luisetti |D Maurizio |e joint author | |
| 700 | 1 | |a Corti |D Davide |e joint author | |
| 700 | 1 | |a Lanzavecchia |D Antonio |e joint author | |
| 773 | 0 | |t Nature Communications |d London : Nature Publishing Group |g 6, p. 7375 |x 2041-1723 | |
| 856 | 4 | 0 | |u http://hdl.handle.net/20.500.11850/102531 |q text/html |z WWW-Backlink auf das Repository (Open access) |
| 908 | |D 1 |a Journal Article |2 ethresearch | ||
| 950 | |B ETHRESEARCH |P 856 |E 40 |u http://hdl.handle.net/20.500.11850/102531 |q text/html |z WWW-Backlink auf das Repository (Open access) | ||
| 950 | |B ETHRESEARCH |P 700 |E 1- |a Piccoli |D Luca |e joint author | ||
| 950 | |B ETHRESEARCH |P 700 |E 1- |a Campo |D Ilaria |e joint author | ||
| 950 | |B ETHRESEARCH |P 700 |E 1- |a Fregni |D Chiara S. |e joint author | ||
| 950 | |B ETHRESEARCH |P 700 |E 1- |a Fernandez Rodriguez |D Blanca M. |e joint author | ||
| 950 | |B ETHRESEARCH |P 700 |E 1- |a Minola |D Andrea |e joint author | ||
| 950 | |B ETHRESEARCH |P 700 |E 1- |a Sallusto |D Federica; id_orcid 0000-0003-3750-2752 |e joint author | ||
| 950 | |B ETHRESEARCH |P 700 |E 1- |a Luisetti |D Maurizio |e joint author | ||
| 950 | |B ETHRESEARCH |P 700 |E 1- |a Corti |D Davide |e joint author | ||
| 950 | |B ETHRESEARCH |P 700 |E 1- |a Lanzavecchia |D Antonio |e joint author | ||
| 950 | |B ETHRESEARCH |P 773 |E 0- |t Nature Communications |d London : Nature Publishing Group |g 6, p. 7375 |x 2041-1723 | ||
| 898 | |a BK010053 |b XK010053 |c XK010000 | ||
| 949 | |B ETHRESEARCH |F ETHRESEARCH |b ETHRESEARCH |j Journal Article |c Open access | ||