Oner Ozdemir

Development of multiple food allergies in children taking tacrolimus after heart and liver transplantation

Abstract: Angioedema and chronic diarrhea in patients taking immunosuppressants are not always because of side effects and could be a new onset of food allergy. Our aim is to discuss the pathogenesis and treatment of the post‐transplant development of food allergies. The first patient was receiving tacrolimus subsequent to heart transplantation and developed angioedema after consumption of dairy products at 12 months after transplantation. He was found to be allergic to multiple foods by both RAST and ImmunoCAP tests. The second patient with argininosuccinic aciduria, post‐liver transplant, also received tacrolimus and developed chronic non‐mucoid/bloody diarrhea at seven months following transplantation. ImmunoCAP test was positive only for egg white and peanuts. Biopsy showed eosinophilic infiltration of the mucosa from the stomach to the rectum. Elimination diets in both patients resolved the symptoms. These cases suggest a direct relationship between tacrolimus and development of food allergy.

Mechanisms of superior anti-tumor cytotoxic response of interleukin 15-induced lymphokine-activated killer cells.

Interleukin (IL) 15 is one of the main cytokines controlling cytotoxic lymphocyte survival and growth. Despite its receptor and functional similarity to IL-2, IL-15 affects a wider target cell population and utilizes different mechanisms in cell activation. The role of IL-15 in lymphokine-activated killer (LAK) cell generation in vitro and potential mechanisms of cytotoxicity compared with equivalent low concentration of IL-2 with or without mitogens (phytohemoglutinin (PHA) and anti-CD3 antibody) have been investigated in this study. IL-15 treatment resulted in moderate cell proliferation over 7 days, whereas IL-2 treatment was associated with decreased cell numbers. Unlike IL-2 in combination with mitogens, IL-15 caused increases in both cytotoxic T lymphocytes (CTL) and CD56+ LAK cells, particularly cytokine-induced killer and cytolytic natural killer T-cell (CNK-T) subpopulations, which are known to be highly effective in cytotoxicity. IL-15 also increased overall perforin and tumor necrosis factor-α expression and more prominently in CTLs. Consequently, IL-15 resulted in superior cytotoxicity against two different NK-sensitive (human K-562 and murine YAC-1) and LAK-sensitive (human Daudi and Raji) cell lines compared with other cytokine combinations. There was also no contribution of mitogens to IL-2-induced cytotoxicity. In conclusion, IL-15 at the concentration of 10 ng/mL used in this study causes moderate proliferation and superior cytotoxicity of LAK cells in vitro that was associated with induction of a specific LAK cell subpopulation profile and related cellular killing mechanisms. These results are encouraging for potential use of IL-15 as part of immunotherapy.

Food Intolerances and Eosinophilic Esophagitis in Childhood

Food intolerance is an adverse reaction to a particular food or ingredient that may or may not be related to the immune system. A deficiency in digestive enzymes can also cause some types of food intolerances like lactose and gluten intolerance. Food intolerances may cause unpleasant symptoms, including nausea, bloating, abdominal pain, and diarrhea, which usually begin about half an hour after eating or drinking the food in question, but sometimes symptoms may delayed up to 48xa0h. There is also a strong genetic pattern to food intolerances. Intolerance reactions to food chemicals are mostly dose-related, but also some people are more sensitive than others. Diagnosis can include elimination and challenge testing. Food intolerance can be managed simply by avoiding the particular food from entering the diet. Babies or younger children with lactose intolerance can be given soy milk or hypoallergenic milk formula instead of cow’s milk. Adults may be able to tolerate small amounts of troublesome foods, so may need to experiment. Eosinophilic esophagitis (EE) is defined as isolated eosinophilic infiltration in patients with reflux-like symptoms and normal pH studies and whose symptoms are refractory to acid-inhibition therapy. Food allergy, abnormal immunologic response, and autoimmune mechanisms are suggested as possible etiological factors for EE. This article is intended to review the current literature and to present a practical approach for managing food intolerances and EE in childhood.

40 CAN AEROLYSIN SERVE AS A SURROGATE MARKER FOR MEASURING LAK CELL-MEDIATED CYTOTOXICITY IN SHORT TERM?

Background Aerolysin is a pore-forming toxin produced by Aeromonas hydrophila and interacts with targets through binding to glycosylphosphatidyl inositol-anchored proteins, subsequently forming a pore in the membrane. Perforin (PFP), a prototype of pore-forming proteins, is the central element of cell-mediated cytotoxicity and induces apoptosis through granule-exocytosis. Aims Since PFP is pivotal to cell-mediated cytotoxicity in short term and due to similarities between PFP and aerolysin action, we investigated the correlation between aerolysin cytotoxicity and short-term lymphokine activated killer (LAK) cell-mediated cytotoxicity against human tumor cells. Methods We studied the effect of active aerolysin (2 × 10-10M) against 8 tumor cell lines and 5 acute myeloid leukemia (AML) patients. AML cells K562, U937, CMK, Meg-01, HL-60 and resistant central nervous system tumor cells (HTB-11, HTB-12 and HTB-14) were included in this study. Tumor cell type selection was based on their sensitivity against LAK cell-mediated cytotoxicity. Aerolysin cytotoxicity was assessed at 7 different time points up to 4 hours of incubation consistent with the known optimal cell kill period mediated by PFP. Drug and aerolysin cytotoxicity was measured by flow cytometric detection of annexin V/PI-positive cells, DiOC6(3) /PI staining and further quantification of fluorosphere-adjusted events. LAK cell-mediated cytotoxicity against tumor cell lines and patient samples was measured by our established method flow cytometric cell-mediated cytotoxicity assay. Results In timing studies, aerolysin treatment reached peak cytotoxicity around 2 hours of incubation similar to LAK cytotoxicity. U937 was the most sensitive cell type to both LAK cells and aerolysin. Some cells were very resistant to LAK killing and aerolysin at the concentration used. There was significant correlation between aerolysin cytotoxicity and LAK cell-mediated kill at 2 hours in cell lines and patient samples (r = .99, p < .001; r = .85, p = .035, respectively). However, there was no correlation between drug cytotoxicity and LAK cell-mediated cytotoxicity or aerolysin-induced cell kill. Conclusion Aerolysin sensitivity may be used as a surrogate marker for the assessment of in vitro LAK cell-mediated tumor cell kill caused by granule/exocytosis pathway.