Schematic of the proposed mechanism of innate immune regulation by GM-CSF autoantibodies showing the relationship between endogenous GM-CSF autoantibody level (abscissa), GM-CSF–dependent myeloid cell functions, and GM-CSF bioactivity (ordinate). More than a range of low autoantibody levels present in healthy subjects, myeloid cell functions vary inversely with level of GM-CSF autoantibodies (ordinate, ▨) and increased levels of GM-CSF (eg, present at inflammatory sites or from exogenous administration) increase myeloid cell functions above baseline levels by a mechanism known as “GM-CSF priming” (ordinate, ■). At and above GM-CSF autoantibody levels sufficient to completely neutralize GM-CSF bioactivity (eg, the critical threshold), GM-CSF–stimulated myeloid cell functions are minimal or zero (ordinate, □) and the risk of PAP is increased.