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23 24 25 2 26 ABSTRACT 27 28 Eosinophils are the prominent inflammatory cell involved in allergic asthma, atopic dermatitis, 29 eosinophilic esophagitis, and hypereosinophilic syndrome and are found in high numbers in local tissue 30 and/or circulating blood of affected patients. There is recent interest in a family of alarmins, including 31 TSLP, IL-25 and IL-33, that are epithelial-derived and released upon stimulation of epithelial cells. Several 32 genome wide association studies have found SNPs in genes encoding IL-33 to be risk factors for asthma. 33 In two studies examining the direct role of IL-33 in eosinophils, there were differences in eosinophil 34 responses. We sought to further characterize activation of eosinophils with IL-33 compared to activation 35 by other cytokines and chemokines. We assessed IL-33 stimulated adhesion, degranulation, chemotaxis 36 and cell surface protein expression in comparison to IL-3, IL-5, and eotaxin-1 on human eosinophils. Our 37 results demonstrate that IL-33 can produce as potent or more eosinophil activation than IL-3, IL-5 and 38 eotaxin-1. Thus, when considering specific cytokine targeting strategies, IL-33 will be important to 39 consider for modulating eosinophil function. 40 41 42 111 Mg 2 + and washed with 3 times with HBSS. Cells, 1x10 4 eosinophils, were added to each well along with 112 the respective cytokines (1ng/ml final concentration). After 30 min at 37°C, wells were washed 3x with 113 HBSS to remove non adherent cells. 100ul of HBSS was added to sample wells and 100ul with 1x10 4114 eosinophils were added to untreated wells to provide "Total" eosinophils for comparison. Eosinophil

Eosinophils are the prominent inflammatory cell involved in allergic asthma, atopic dermatitis, eosinophilic esophagitis, and hypereosinophilic syndrome and are found in high numbers in local tissue and/or circulating blood of affected patients. There is recent interest in a family of alarmins, including TSLP, IL-25 and IL-33, that are epithelial-derived and released upon stimulation of epithelial cells. Several genome wide association studies have found SNPs in genes encoding IL-33 to be risk factors for asthma. In two studies examining the direct role of IL-33 in eosinophils, there were differences in eosinophil responses. We sought to further characterize activation of eosinophils with IL-33 compared to activation by other cytokines and chemokines. We assessed IL-33 stimulated adhesion, degranulation, chemotaxis and cell surface protein expression in comparison to IL-3, IL-5, and eotaxin-1 on human eosinophils. Our results demonstrate that IL-33 can produce as potent eosinophil activation as IL-3, IL-5 and eotaxin-1. Thus, when considering specific cytokine targeting strategies, IL-33 will be important to consider for modulating eosinophil function.

Peliosis hepatis is a rare condition characterized by blackish-blue blood-filled cavities in hepatic parenchyma caused by dilatation of hepatic sinusoids. Peliosis hepatis has been described in secondary immunodeficiencies and certain medications. We present the first case of peliosis hepatis in a patient with a primary immunodeficiency, common variable immunodeficiency. A 44-year-old African-American male presented with gastrointestinal bleeding and elevated liver function tests. His medical history included common variable immunodeficiency and chronic kidney disease. The patient had jaundice, regenerative nodules on liver pathology, and low immunoglobulin levels. A magnetic resonance imaging of the abdomen with contrast revealed a cirrhotic liver, a 5 × 3 cm lesion, and poorly defined nodules which had decreased enhancement. A computed tomography-guided liver biopsy revealed peliosis hepatis, focal nodular hyperplasia, and fibrosis. No other etiology of his liver disease was found. The etiology of peliosis hepatis in patients with primary immunodeficiencies remains unclear. Additional studies are needed to understand the underlying mechanisms.

RATIONALE: Hypereosinophilia is defined as a peripheral blood absolute eosinophil count (AEC) of >0.5 x10 9 /L, while severe hypereosinophilia is defined as an AEC of >1.5x10 9 /L. Much has been published on hypereosinphilia in the adult literature; however, there is limited literature on pediatric patients with hypereosinophilia (especially severe eosinophila) or hypereosinophilic syndrome (HES). The goal of this study was to characterize children with severe hypereosinophilia hospitalized in a tertiary care center. METHODS: We reviewed the charts of allergy/immunology consults performed from January 2013-April 2016 at Saint Louis Children's Hospital. Children were included in this study if their AEC was >1.5x10 9 at the time of the allergy/immunology consult. Data was collected on demographics, comorbidities, treatment, laboratory data, and clinical outcomes. Patients were sorted into diagnostic groups that included: overlap hypereosinophilic syndrome, allergic/atopy, hypereosinophilic syndrome myeloproliferative subtype, immunodeficiency, and unknown. RESULTS: We reviewed that chart of 289 inpatient consults and 13 met our inclusion criteria. Mean age at presentation was 19.5 months (range 1-49 months). Mean peak peripheral blood AEC was 5.5x10 9 /L (range 1800-12,524x10 9 /L). Four patients were found to have atopic driven eosinophilia, three with an underlying primary immunodeficiency, two with HES myeloproliferative variant, one with overlap HES. Four patients had an unknown etiology. Mortality in our cohort was 23%. CONCLUSIONS: Severe hypereosinophilia was the reason for 4.5% of inpatient Allergy/Immunology consults. A variety of reasons caused underlying eosinophilia. As many life threatening conditions were identified, prompt recognition of the underlying pathology is critical for proper treatment.