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. 2009 Dec 31;361(27):2679-81.
doi: 10.1056/NEJMc0904077.

Human GM-CSF autoantibodies and reproduction of pulmonary alveolar proteinosis

Takuro Sakagami, Kanji Uchida, Takuji Suzuki, Brenna C Carey, Robert E Wood, Susan E Wert, Jeffrey A Whitsett, Bruce C Trapnell, Maurizio Luisetti

Human GM-CSF autoantibodies and reproduction of pulmonary alveolar proteinosis

Takuro Sakagami et al. N Engl J Med. .
No abstract available

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Conflict of interest statement

No other potential conflict of interest relevant to this letter was reported.

Figures

Figure 1
Figure 1. Effects of Human GM-CSF Autoantibodies in Nonhuman Primates
Healthy nonhuman primates (Macaca fascicularis) were pretreated with rituximab and cyclophosphamide to block the immune response to human immunoglobulins and were injected with human granulocyte–macrophage colony-stimulating factor (GM-CSF) autoantibodies derived from a patient with idiopathic pulmonary alveolar proteinosis (purified as previously described) or saline, as a control. Panel A shows the histologic appearance of the lung of a macaque injected with GM-CSF autoantibodies (hematoxylin and eosin). Well-preserved alveolar walls (arrowhead), granular eosinophilic material (thick arrows), and numerous foamy alveolar macrophages filling alveoli (thin arrow) are shown. The scale bar represents 50 μm. Panel B shows immunostaining of the lung for surfactant protein B (brown areas), with nuclear fast red counterstaining. The scale bar represents 100 μm. Panel C shows oil red O staining of lipid in alveolar macrophages and alveolar spaces. The scale bar represents 50 μm. Panel D shows the ultrastructure of alveolar macrophages (top panels) and lung-lavage sediment (bottom left panel) from a passively immunized macaque and a typical normal alveolar macrophage from a control macaque (bottom right panel). Alveolar macrophages from the immunized macaque are engorged with lipid droplets (top left panel) and lamellar bodies (top right panel), and the lung-lavage sediment contains copious amounts of lamellar material that is typical of lung surfactant (uranyl acetate–lead citrate staining for all four panels). The scale bar represents 2 μm. Panel E shows the number of inclusions of lipid droplets and lamellar bodies in alveolar macrophages obtained from bronchoalveolar-lavage specimens from macaques injected with GM-CSF autoantibodies and from a control. Inclusion bodies were counted by means of electron photomicrographs of at least 100 randomly selected macrophages from each macaque. The asterisks indicate P≤0.01 for the comparison with the corresponding control that did not receive antibodies, calculated with the use of Student’s t-test. Panel F shows the neutralizing capacity of GM-CSF autoantibodies isolated directly from a patient with idiopathic pulmonary alveolar proteinosis and from a passively immunized macaque; these autoantibodies were measured according to the CD11b stimulation index. Neither of the autoantibodies had any effects on mouse neutrophils, in contrast to anti-mouse GM-CSF antibodies that blocked GM-CSF stimulation completely; this shows that specificity was also retained during passive immunization (not shown). The asterisks indicate P≤0.01 for the comparison with the corresponding control that did not receive antibodies, calculated with the use of analysis of variance. In Panels E and F, numeric data were normally distributed, the bars represent the mean of triplicate determinations, and the T bars indicate the standard error.
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References

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