Potential role for a Nematode Pan Allergen (NPA) in Tropical Pulmonary Eosinophilia (TPE)

Abstract Tropical Pulmonary Eosinophilia (TPE) is an asthma-like hyper-responsive syndrome characterized by accumulation of a high number of eosinophils in the lungs leading to severe respiratory morbidity in patients infected with lymphatic filariasis (LF), a helminth parasitic infection that affects 51 million people in 47 different countries worldwide. Subjects showing TPE also have circulating microfilariae (larval stages of LF) and a high titer of parasite-specific IgE in their blood. IgE and eosinophils are thought to play a major role in TPE pathology. However, specific antigens that are released from microfilariae responsible for generating the IgE antibodies in TPE are not known. Therefore, in this study, we screened a phage displayed cDNA expression library of Wuchereria bancrofti microfilaria with human monoclonal IgE antibodies generated from B cells isolated from TPE patients. The iterative screening identified WbNPA (Nematode Pan Allergen) and WbTCTP (Translationally Controlled Tumor Protein) as IgE antibody binding antigens. Subsequent analysis showed that rWbNPA and rWbTCTP can result in the release of histamine from mast cells in an IgE-dependent and independent manner. rWbNPA can induce accumulation of eosinophils in the peritoneal cavity of mice and can trigger the secretion of IL-2 and TNF-α from alveolar macrophages. These results suggest that WbNPA and WbTCTP have a potential role in the pathology of TPE in LF infections.