SummaryEpidemiological data show that allergic children have a different intestinal flora from healthy children with higher levels of Clostridia and lower levels of Bifidobacteria. Nonetheless, Bifidobacteria and Lactobacilli are found more commonly in the composition of the intestinal flora of non-allergic children. Probiotics are ingested live microbes that can modify intestinal microbial populations in a way that benefits the host and they are represented mainly by Lactobacilli. Enhanced presence of probiotic bacteria in the intestinal microbiota is found to correlate with protection against atopy. There is also very promising evidence to recommend the addition of probiotics to foods for the prevention and treatment of allergic diseases. Clinical improvement, especially in allergic rhinitis and immunoglobulin (Ig)E-sensitized (atopic) eczema, has been reported in most of the published studies. However, clinical benefit of probiotic therapy depends upon numerous factors, such as type of bacterium, dosing regimen, delivery method and other underlying host factors, e.g. the age and diet of the host. Selection of the most beneficial probiotic strain, the dose and the timing of supplementation still need to be determined. This review helps understanding of the role of probiotics in various allergic diseases, explaining laboratory and clinical data in light of recent literature.

Melatonin has a variety of functions in human physiology and is involved in a number of pathological events including neoplastic processes. The tissue protective actions of melatonin are attributed to its antioxidant activity though, under certain conditions, melatonin might also exert oxidant effects, particularly in cancer cells. This study evaluated the effects of 10(-5) and 10(-3) m concentrations of melatonin on human leukemia cells. Moderate cytotoxic effects of melatonin at 10(-3) m concentrations were observed in CMK, Jurkat and MOLT-4 cells which was associated with significant reactive oxygen species (ROS) generation. Melatonin treatment was not associated with significant cytotoxicity in HL-60 cells, although the generation of ROS was significantly increased. K562 and Daudi cells did not appear to be effected by melatonin treatment. Cellular membrane lipid peroxidation was not influenced by melatonin with the exception of CMK cells. Cell cycle kinetics were not affected in melatonin-treated samples, again with the exception of CMK cells which showed increased apoptosis. Melatonin, therefore, induces the production of ROS that may be associated with cytotoxicity depending on the concentration of melatonin in some leukemia cells and does not appear to stimulate leukemia cell growth. These pro-oxidant actions of melatonin may assist in limiting leukemic cell growth.

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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.

Background: In addition to 51 chromium release assay, flow cytometric methods have been described to assess in vitro cell-mediated cytotoxicity. In this report, we describe a new flow cytometric approach for determination of in vitro cell-mediated cytotoxicity utilizing three-color flow cytometric assay. Methods: This method is based on monoclonal antibody staining of either effector or target cells to evaluate cytotoxicity with increased accuracy by utilizing fluorospheres for calibration. The basic strategy involves labeling effector or target cells with a specific fluorescentconjugated monoclonal antibody, in addition to staining with annexinV-FITC and propidium iodide to identify apoptotic/dead cells. The effector and target cell populations as well as conjugates were clearly and easily identified by this approach. Results: We obtained significant correlation between cytotoxicity calculated by this technique and 51 chromium

Development of the child's immune system tends to be directed toward a T-helper 2 (Th2) phenotype in infants. To prevent development of childhood allergic/atopic diseases, immature Th2-dominant neonatal responses must undergo environment-driven maturation via microbial contact in the early postnatal period. Lactic acid bacteria and bifidobacteria are found more commonly in the composition of the intestinal flora of nonallergic children. Epidemiological data also showed that atopic children have a different intestinal flora from healthy children. Probiotics are ingested live health-promoting microbes that can modify intestinal microbial populations in a way that benefits the host; and enhanced presence of probiotic bacteria in the intestinal microbiota is found to correlate with protection against atopy. There is insufficient but very promising evidence to recommend the addition of probiotics to foods for prevention and treatment of allergic diseases, especially atopic dermatitis. Clinical improvement especially in allergic rhinitis and IgE-sensitized (atopic) eczema has been reported too. Literature data for food allergy/hypersensitivity and asthma are not adequate for this guaranteed conclusion; however, clinical benefit of probiotic therapy depends on numerous factors, such as type of bacterium, dosing regimen, delivery method, and other underlying host factors, e.g., the age and diet of the host. The selection of the most beneficial probiotic strain, the dose, and the timing of supplementation still need to be determined. Accordingly, probiotics can not be recommended generally for primary prevention of atopic disease; and if probiotics are used in atopic infants/children for any reason, such as therapy or prevention, cautionary approach ought to be taken.

Transplant-acquired allergy (TAA) was firstly described as transplant-acquired food allergy (TAFA) after bone marrow transplantations and mostly observed in a transient form. The picture is complicated by numerous case reports of TAFA after the receipt of liver grafts from donors with no documented history of food allergy. The estimated prevalence of TAFA among young children in the literature has been documented in various studies ranging from 6% to 57%. Although TAA is mostly found to be associated with liver transplantation; it has been recently reported to be related with heart, intestinal, lung and even renal transplantations in adults. Previous reviews of published cases of liver TAA misleadingly emphasized the predominance of children and the absence of TAA in cardiac, pulmonary, and renal transplant recipients. In different studies, the male/female ratio is equal. Literature data suggest that children with TAFA typically present within the first year after surgery and are typically allergic to multiple foods. The pathogenesis of TAA is not still completely understood. Most of the studies support the concept that the functioning liver itself, and not only tacrolimus immunosuppression, is one of the main contributors to TAA in these patients. In the light of recent findings, other possible mechanisms can be summarized as following: (1) the recovery of delayed type hypersensitivity; (2) late manifestation of food allergy; (3) intestinal injury as well as inhibition of cellular energy production by tacrolimus; and (4) transfer of food-specific IgE or lymphocytes. Thus, interplay between hematopoietic cells from the transplanted organ and recipient specific factors (e.g., younger age and atopic background) seem to underlie the development of TAA. Most patients will have symptomatic improvement following reduced immunosuppression and an appropriately restricted diet. Nevertheless, some studies suggest that atopic diseases occur in some of pediatric liver transplant recipients, with manifestations including food allergy, eczema, allergic rhinitis, and asthma. More studies would be needed including greater number of patients to determine whether TAA is transient or not in pediatric/adult solid organ recipients.

Background Genetic deficiencies of immune system, referred to as inborn errors of immunity (IEI), serve as a valuable model to study human immune responses. In a multicenter prospective cohort, we evaluated the outcome of SARS‐CoV‐2 infection among IEI subjects and analyzed genetic and immune characteristics that determine adverse COVID‐19 outcomes. Methods We studied 34 IEI patients (19M/15F, 12 [min: 0.6‐max: 43] years) from six centers. We diagnosed COVID‐19 infection by finding a positive SARS‐CoV‐2 PCR test ( n = 25) and/or a lung tomography scoring (CORADS) ≥4 ( n = 9). We recorded clinical and laboratory findings prospectively, fitted survival curves, and calculated fatality rates for the entire group and each IEI subclass. Results Nineteen patients had combined immune deficiency (CID), six with predominantly antibody deficiency (PAD), six immune dysregulation (ID), two innate immune defects, and one in the autoinflammatory class. Overall, 23.5% of cases died, with disproportionate fatality rates among different IEI categories. PAD group had a relatively favorable outcome at any age, but CIDs and IDs were particularly vulnerable. At admission, presence of dyspnea was an independent risk for COVID‐related death (OR: 2.630, 95% CI; 1.198–5.776, p < .001). Concerning predictive roles of laboratory markers at admission, deceased subjects compared to survived had significantly higher CRP, procalcitonin, Troponin‐T, ferritin, and total‐lung‐score ( p = .020, p = .003, p = .014, p = .013, p = .020; respectively), and lower absolute lymphocyte count, albumin, and trough IgG ( p = .012, p = .022, p = .011; respectively). Conclusion Our data disclose a highly vulnerable IEI subgroup particularly disadvantaged for COVID‐19 despite their youth. Future studies should address this vulnerability and consider giving priority to these subjects in SARS‐Cov‐2 therapy trials.