The study examines a novel mouse model for autoimmune pulmonary alveolar proteinosis (aPAP), the most prevalent clinical form of pulmonary alveolar proteinosis (PAP) in patients. PAP is a potentially deadly disease whereby disease-causing antibodies impair the functions of key cells in the lungs.
Currently, it is not known how these antibodies are generated. This process leads to a buildup of fluid in the lungs, causing the patient to have difficulty breathing.
“This research is important because there are no rodent models that spontaneously develop the autoimmune form of PAP to date,” Ferretti said. “Thus, it is difficult to study the early pathological mechanisms that result in aPAP.”
“Previous work from our lab and others show that mice lacking the cell signaling molecule Rasgrp1 spontaneously develop autoimmune features that are similar to the autoimmune disease systemic lupus erythematosus,” Ferretti said. “In addition to these features, we describe in this study another autoimmune feature in Rasgrp1-deficient mice that manifests in the lung and closely mimics the human condition known as aPAP.”
Ferretti said the data from his study strongly suggests that Rasgrp1-deficient mice are the first rodent model for aPAP. “We are now digging deeper into the mechanisms that cause disease in this model and we plan to search for similar defects in human patients with aPAP, which could potentially expose future treatments,” he said.
Dr. Robert Barrington, assistant professor in the department of microbiology and immunology at the USA College of Medicine, is Ferretti’s primary mentor and senior author on the study. In 2015, the American Lung Association awarded Dr. Barrington a two-year research grant totaling $80,000 to further his research on PAP.
“Dr. Barrington has played an indispensable role for both this study and for my training in general,” Ferretti said. “Without his support and guidance we would not have been able to publish this study.”
The Journal of Immunology is published by the American Association of Immunologists and publishes novel, peer-reviewed findings in all areas of experimental immunology. Click here to view Ferretti’s abstract.
Click here to learn more about Dr. Barrington’s research grant from the American Lung Society.
