Using a cohort of more than 200 subjects with a wide variety of eosinophilic disorders, ranging from benign eosinophilia to eosinophilic leukemia, we have continued to look for new markers that distinguish between variants of hypereosinophilic syndrome. Assessment of serum and surface IL-5 receptor levels in a large cohort of patients with eosinophilia and/or mastocytosis suggests that regulation of this receptor occurs in vivo. This may have important implications in the setting of recently developed therapeutic agents targeting IL-5 and its receptor. We have developed an assay to examine the effects of such agents on IL-5 receptor bearing cells in the bone marrow using colony forming assays and flow cytometry. We have previously described a family with an autosomal dominant variant of hypereosinophilic syndrome that maps to chromosome 5q31-33. Exhaustive attempts to identify the gene responsible for this condition, including candidate gene sequencing, array CGHY, expression analysis, 454 sequencing of the region upstream of IL-5, in collaboration with John Rioux and Jan Cools, have been unsuccessful to date. High-throughput sequencing of the target region is planned. Fibrosis is one of the most severe complications of eosinophilia and is particularly prevalent in patients with untreated FIP1L1/PDGFRA-positive disease. We have recently completed microarray analysis using eosinophil RNA from FIP1L1/PDGFRA-positive patients before and after imatinib treatment in an effort to identify the factors responsible for the increased prevalence of fibrosis in this condition. Analysis is ongoing. We have continued to study the effects of novel therapies for the treatment of hypereosinophilic syndromes, including monoclonal antibodies to IL-5 and the tyrosine kinase inhibitor, imatinib. We have also begun to explore new therapeutic approaches for the treatment of refractory L-HES in collaboration with Drs. Janik and Morris (NCI). Additionally, we have expanded our studies of monoclonal antibodies targeting IL-5 to explore the role of eosinophilia in post-treatment reactions in the filarial infection, loiasis, since we have previously demonstrated an association between eosinophilia and side effects of DEC treatment in these patients.
| Kuang, Fei Li; Fay, Michael P; Ware, JeanAnne et al. (2018) Long-Term Clinical Outcomes of High-Dose Mepolizumab Treatment for Hypereosinophilic Syndrome. J Allergy Clin Immunol Pract 6:1518-1527.e5 |
| Panch, Sandhya R; Bozik, Michael E; Brown, Thomas et al. (2018) Dexpramipexole as an oral steroid-sparing agent in hypereosinophilic syndromes. Blood 132:501-509 |
| Khoury, P; Stokes, K; Gadkari, M et al. (2018) Glucocorticoid-induced eosinopenia in humans can be linked to early transcriptional events. Allergy 73:2076-2079 |
| Khoury, Paneez; Akuthota, Praveen; Ackerman, Steven J et al. (2018) Revisiting the NIH Taskforce on the Research needs of Eosinophil-Associated Diseases (RE-TREAD). J Leukoc Biol 104:69-83 |
| Groves, Daniel W; Klion, Amy D; Chen, Marcus Y et al. (2018) Swiss cheese heart. Eur Heart J 39:255-256 |
| Herrick, Jesica A; Legrand, Fanny; Gounoue, Raceline et al. (2017) Posttreatment Reactions After Single-Dose Diethylcarbamazine or Ivermectin in Subjects With Loa loa Infection. Clin Infect Dis 64:1017-1025 |
| Ma, Chi A; Xi, Liqiang; Cauff, Brian et al. (2017) Somatic STAT5b gain-of-function mutations in early onset nonclonal eosinophilia, urticaria, dermatitis, and diarrhea. Blood 129:650-653 |
| Wechsler, Michael E; Akuthota, Praveen; Jayne, David et al. (2017) Mepolizumab or Placebo for Eosinophilic Granulomatosis with Polyangiitis. N Engl J Med 376:1921-1932 |
| Khoury, Paneez; Makiya, Michelle; Klion, Amy D (2017) Clinical and Biological Markers in Hypereosinophilic Syndromes. Front Med (Lausanne) 4:240 |
| Kuang, Fei Li; Klion, Amy D (2017) Biologic Agents for the Treatment of Hypereosinophilic Syndromes. J Allergy Clin Immunol Pract 5:1502-1509 |
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