Electronic Resource
Neutralization and clearance of GM-CSF by autoantibodies in pulmonary alveolar proteinosis
| العنوان: | Neutralization and clearance of GM-CSF by autoantibodies in pulmonary alveolar proteinosis |
|---|---|
| المؤلفون: | Piccoli, Luca, Campo, Ilaria, Fregni, Chiara Silacci, Fernandez Rodriguez, Blanca Maria, Minola, Andrea, Sallusto, Federica, Luisetti, Maurizio, Corti, Davide, Lanzavecchia, Antonio |
| بيانات النشر: | 2019-07-31T06:25:32Z |
| نوع الوثيقة: | Electronic Resource |
| مستخلص: | 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. |
| URL: | |
| الاتاحة: | Open access content. Open access content |
| ملاحظة: | English |
| Other Numbers: | CHRRO oai:doc.rero.ch:20190730104929-WI 1156712908 |
| المصدر المساهم: | RERO-LIBR NETWORK OF WESTERN SWITZERLAND From OAIster®, provided by the OCLC Cooperative. |
| رقم الانضمام: | edsoai.on1156712908 |
| قاعدة البيانات: | OAIster |
| الوصف غير متاح. |