Clinical/Therapeutic Studies Of Filariasis &Related Dis

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Abstract

To understand better the pathogenesis of filarial infections (onchocerciasis, loiaisis, lymphatic filarasis) clinical assessments of patients with these and other related non-filarial (strongyloides, malaria) infections have been studied in detail. Moreover, the post-treatment inflammatory responses and the underlying mechanisms in their induction have been detailed. In particular, the control of eosinophil induction and cell trafficking to sites of post-treatment inflammation has been studied. The importance of the Wolbachia endosymbiont both as a therapeutic target and as a inducer of inflammation has been detailed as well. Understanding of the pathogenesis of eosinophil-related disorders has been a major focus of our clinically related studies Multiple groups of hypereosinophilic patients (parasite-infected, familial hypereosinophilia, idiopathic hypereosinophilic syndrome, benign hypereosinophilia, episodic angioedema with eosinophilia) have been assessed clinically; moreover, lymphocytes (and their subsets) and eosinophils have been examined functionally and at the molecular level (human microarrays and RT-PCR) to identify the molecules and pathways involved in conditions associated with increased blood and tissue eosinophilia. A clinical subgroup of patients with hypereosinophilic syndrome and elevated serum tryptase levels was identified and shown to have a myeloproliferative disorder characterized by male predominance, eosinophil activation, abnormal mast cells, and tissue fibrosis. This clinical syndrome was subsequently shown to correlate with therapeutic responsiveness to imatinib mesylate and the presence of a recently described fusion tyrosine kinase, FIP1L1/PDGFRA (Klion et al, Blood,2004). In contrast, a detailed clinical and immunologic study of patients with familial eosinophilia demonstrated a relative lack of eosinophil activation despite high levels of peripheral eosinophilia, consistent with the benign clinical course observed in the patients studied.