Title: Granulocyte/Macrophage Colony-Stimulating Factor Autoantibodies and Myeloid Cell Immune Functions in Healthy Individuals
نویسندگان
چکیده
High levels of granulocyte/macrophage-colony stimulating factor (GM-CSF) autoantibodies are thought to cause pulmonary alveolar proteinosis (PAP), a rare syndrome characterized by myeloid dysfunction resulting in pulmonary surfactant accumulation and respiratory failure. Paradoxically, GM-CSF autoantibodies have been reported to occur rarely in healthy people and routinely in pharmaceutical intravenous immunoglobulin (IVIG) purified from serum pooled from healthy individuals. These findings suggest that either GM-CSF autoantibodies are normally present in healthy individuals at low levels that are difficult to detect or that serum pooled for IVIG purification may include asymptomatic individuals with high levels of GM-CSF autoantibodies. Using several experimental approaches, GM-CSF autoantibodies were detected in all healthy individuals evaluated (n=72) at low levels sufficient to rheostatically regulate multiple myeloid functions. Serum GM-CSF was more abundant than previously reported but more that 99% was bound and neutralized by GM-CSF autoantibody. The critical threshold of GM-CSF autoantibodies associated with the development of PAP was determined. Results demonstrate that free serum GM-CSF is tightly maintained at low levels, identify a novel potential mechanism of innate immune regulation, help define the therapeutic window for potential clinical use of GM-CSF autoantibodies to treat inflammatory and autoimmune diseases, and have implications for the pathogenesis of PAP.
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تاریخ انتشار 2008