Mendelian inheritance of elevated serum tryptase associated with atopy and connective tissue abnormalities.

also suggest that early initiation of PEG-ADA should be considered for ADA-deficient patients suffering from PAP, particularly when rapid hematopoietic stem cell transplantation cannot be performed. Our study also has several significant limitations. While we focused on AMs, future studies are needed to assess the role of pneumocytes and other lung cell abnormalities in the development of PAP in ADA deficiency. In addition, although we found that phagocytosis of IgG-coated beads by ADA-deficient AMs was normal, surfactant uptakewas not directly determined.Moreover, AM function differs between humans and mice; hence, further studies with AMs isolated from ADA-deficient patients or developed from induced pleuri-potent stem cells of ADAdeficient patients will be required. In conclusion, we establish here that ADA-KO mice develop PAP, in association with adenosine, surfactant, and AM abnormalities, and that early restoration of blood ADA activity can prevent PAP and early lethality in ADA-deficient mice.