| Description |
Hypereosinophilic syndrome (HES), first defined by Cushid et al. in 1975, is a heterogeneous disorder characterized by striking eosinophilia with damage to a variety of organs. Studies have shown eosinophilia in a large portion of HES patients to be the result of an overproduction of interleukin 5 (IL-5) by T-helper 2 (Th2) cells. IL-5 is the most significant eosinophilopoetic cytokine and plays a crucial role in production, migration, activation and survival of eosinophils. This understanding led researchers to develop an antibody directed against IL-5 as a novel approach to HES treatment. Initial studies utilizing this anti-IL-5 antibody, known as mepolizumab, have shown it to be extremely effective at rapidly reducing blood and tissue eosinophil counts with remarkably few side effects. Although the positive results of mepolizumab treatment are evident, the exact mechanisms of effectiveness, as well as the cellular response to the drug, remain unclear. The primary aim of this thesis was to study the effects of mepolizumab treatment on monocyte and granulocyte populations. To accomplish this, leukocytes obtained from patients receiving placebo, patients receiving mepolizumab and a control group were immunofluorescently stained using a variety of cell surface antigen specific antibodies conjugated to four different fluorophores. After staining, the cells were analyzed by flow cytometry and these data were collected and evaluated to assess potential differences as a result of mepolizumab treatment. The objective was to identify significant abnormal populations or surface antigen differences among the three patient groups. Clinically significant differences were not observed among the three patient groups and antigen biomarker expression considered abnormal for monocytes or granulocytes were not discovered, leading to the following conclusions. First, clear explanations for the heterogeneity of hypereosinophilic syndrome, as well as differentiating characteristics of disease subgroups do not appear to lie within monocyte and granulocyte populations, when evaluated using selected study biomarkers. Second, the lack of cellular biological modification among the three patient groups supports the hypothesis that mepolizumab may be a safe and effective treatment option for patients suffering from hypereosinophilic syndrome. |
