Caroline Nilsson

EAACI food allergy and anaphylaxis guidelines: diagnosis and management of food allergy

Food allergy can result in considerable morbidity, impact negatively on quality of life, and prove costly in terms of medical care. These guidelines have been prepared by the European Academy of Allergy and Clinical Immunologys (EAACI) Guidelines for Food Allergy and Anaphylaxis Group, building on previous EAACI position papers on adverse reaction to foods and three recent systematic reviews on the epidemiology, diagnosis, and management of food allergy, and provide evidence‐based recommendations for the diagnosis and management of food allergy. While the primary audience is allergists, this document is relevant for all other healthcare professionals, including primary care physicians, and pediatric and adult specialists, dieticians, pharmacists and paramedics. Our current understanding of the manifestations of food allergy, the role of diagnostic tests, and the effective management of patients of all ages with food allergy is presented. The acute management of non‐life‐threatening reactions is covered in these guidelines, but for guidance on the emergency management of anaphylaxis, readers are referred to the related EAACI Anaphylaxis Guidelines.

Anaphylaxis and reactions to foods in children – a population-based case study of emergency department visits

Information about acute reactions to foods among children is limited.

Early Colonization with a Group of Lactobacilli Decreases the Risk for Allergy at Five Years of Age Despite Allergic Heredity

Background Microbial deprivation early in life can potentially influence immune mediated disease development such as allergy. The aims of this study were to investigate the influence of parental allergy on the infant gut colonization and associations between infant gut microbiota and allergic disease at five years of age. Methods and Findings Fecal samples were collected from 58 infants, with allergic or non-allergic parents respectively, at one and two weeks as well as at one, two and twelve months of life. DNA was extracted from the fecal samples and Real time PCR, using species-specific primers, was used for detection of Bifidobacterium (B.) adolescentis, B. breve, B. bifidum, Clostridium (C.) difficile, a group of Lactobacilli (Lactobacillus (L.) casei, L. paracasei and L. rhamnosus) as well as Staphylococcus (S.) aureus. Infants with non-allergic parents were more frequently colonized by Lactobacilli compared to infants with allergic parents (p = 0.014). However, non-allergic five-year olds acquired Lactobacilli more frequently during their first weeks of life, than their allergic counterparts, irrespectively of parental allergy (p = 0.009, p = 0.028). Further the non-allergic children were colonized with Lactobacilli on more occasions during the first two months of life (p = 0.038). Also, significantly more non-allergic children were colonized with B. bifidum at one week of age than the children allergic at five years (p = 0.048). Conclusion In this study we show that heredity for allergy has an impact on the gut microbiota in infants but also that early Lactobacilli (L. casei, L. paracasei, L. rhamnosus) colonization seems to decrease the risk for allergy at five years of age despite allergic heredity.

Peanut component Ara h 8 sensitization and tolerance to peanut

BACKGROUND Isolated Ara h 8 sensitization is suggested to be associated with no or mild symptoms among peanut-sensitized subjects. OBJECTIVE We sought to investigate the occurrence of systemic reactions in children with isolated sensitization to Ara h 8. METHODS Participants were 144 children sensitized to Ara h 8 (≥ 0.35 kU(A)/L) but not to Ara h 1, Ara h 2, or Ara h 3 (<0.35 kU(A)/L). An open oral challenge with peanut was performed in those subjects who did not consume peanut regularly, and an extended IgE reactivity profile was obtained. If the child had a documented history of systemic reactions up to grade I anaphylaxis, double-blind, placebo-controlled food challenges were performed. RESULTS One hundred twenty-nine (89.5%) children were either peanut consumers or did not react to peanut challenge. Another 14 (9.7%) children experienced oral cavity symptoms at the first 2 but not subsequent challenge doses. At the time of the double-blind, placebo-controlled food challenge, 1 boy with a previous mild systemic reaction to peanut experienced lip swelling, stomach cramping, and objective tiredness. Reanalysis of IgE levels showed an increase in peanut IgE levels from 1.5 to 8.8 kU(A)/L, but IgE levels to Ara h 8 remained stable and IgE levels to Ara h 1, Ara h 2, and Ara h 3 were all still less than 0.35 kU(A)/L. The IgE level to Ara h 6 was 0.45 kU(A)/L. CONCLUSION Isolated Ara h 8 sensitization indicates tolerance to peanuts in almost all cases. However, sensitization against thus far unidentified determinants in peanut might cause symptoms in rare cases.

Basophil allergen threshold sensitivity, CD‐sens, IgE‐sensitization and DBPCFC in peanut‐sensitized children

To cite this article: Glaumann S, Nopp A, Johansson SGO, Rudengren M, Borres MP, Nilsson C. Basophil allergen threshold sensitivity, CD‐sens, IgE‐sensitization and DBPCFC in peanut‐sensitized children. Allergy 2012; 67: 242–247.

ImmunoCAP Phadiatop Infant: A New Blood Test for Detecting IgE Sensitisation in Children at 2 Years of Age

Background:  Correct diagnosis of immunoglobulin E (IgE)‐mediated disease is the prerequisite for secondary allergy prevention during early childhood.

Does early EBV infection protect against IgE sensitization

Background There is indirect evidence that an increased infectious burden is associated with a decreased prevalence of IgE-mediated allergy during childhood. Objective To determine whether there is a relation between the serostatus of 13 different viruses and parentally reported infections and IgE sensitization in 2-year-old children. To investigate whether there is an interaction between cytomegalovirus (CMV) and Epstein-Barr virus (EBV) in relation to IgE sensitization. Methods A total of 246 infants were followed prospectively to 2 years of age with clinical examinations, skin prick test, and specific IgE analyses and through analysis of seropositivity against adenovirus, influenza, parainfluenza, respiratory syncytial virus, CMV, EBV, herpes simplex virus, human herpesvirus 6, and varicella-zoster virus. Results There was some evidence that IgE sensitization (24%) tended to be more common among children who were seropositive against few compared with children who were seropositive against many viruses, but this was not statistically significant, and there was no consistent trend across the groups. IgE sensitization was statistically significantly less prevalent at 2 years of age among infants who were seropositive against EBV but not other viruses (adjusted odds ratio, 0.34; 95% CI, 0.14-0.86). The interaction of seropositivity against both CMV and EBV antibodies indicated a further reduction in the risk for IgE sensitization (adjusted odds ratio for interaction, 0.10; 95% CI, 0.01-0.92), indicating effect modification associated with seropositivity against CMV. Conclusion Our results indicate that acquisition of EBV infection during the first 2 years of life is associated with a reduced risk of IgE sensitization, and this effect is enhanced by CMV coinfection.

The utility of peanut components in the diagnosis of IgE-mediated peanut allergy among distinct populations.

BACKGROUND Increasing data suggest that analysis of IgE to peanut components can be clinically helpful and possibly more accurate than IgE to whole peanut. Not all studies examining this topic, however, have used prospective samples, multiple components, and peanut challenges. OBJECTIVE We sought to determine the utility of peanut component testing, using a standardized, commercially available test done before oral peanut challenge in various populations of patients with suspected peanut allergy from 2 different countries. METHODS IgE to whole peanut and the recombinant allergen components Ara h 1, 2, 3, and 8 were analyzed from serum samples drawn before double-blind peanut challenge from 4 distinct cohorts of patients with suspected peanut allergy from 2 nations (United States and Sweden). RESULTS Patients (n = 167; median age, 11.7 years; interquartile range, 7.0-15.0 years) had serum analyzed for peanut components and completed an oral food challenge to peanut. Although IgE to peanut was the most sensitive test (0.93), Ara h 2 was the most specific (0.92) and provided the best positive predictive value (0.94) of all the tests. Ara h 2 was also the best overall diagnostic test by receiver operating characteristic analysis (area under the curve, 0.84; P < .05). CONCLUSIONS In patients with suspected peanut allergy, IgE to peanut is a sensitive test but is not specific. IgE to Ara h 2 is a more specific and more accurate diagnostic test in this sampling of patients with suspected peanut allergy. Given each tests attributes, a stepwise approach to testing may provide clinicians with a way to minimize the need for peanut challenges.

The Expression of Human Natural Killer Cell Receptors in Early Life

Abstract Natural killer (NK) cells play an important role in tumour immunosurveillance and the early defence against viral infections. Recognition of altered cells (i.e. infected‐ or tumour‐cells) is achieved through a multiple receptor recognition strategy which gives the NK cells inhibitory or activating signals depending on the ligands present on the target cell. NK cells originate from the bone marrow where they develop and proliferate. However, further maturation processes and homeostasis of NK cells in peripheral blood are not well understood. To determine the proportions of cells and the expression of NK cell receptors, mononuclear cells from children at three time points during early childhood were compared, i.e. cord blood (CB), 2 and 5 years of age. The proportion of NK cells was high in CB, but the interferon‐γ (IFN‐γ) production low compared to later in life. In contrast, the proportion of T cells was low in CB. This may indicate a deviation of the regulatory function of NK cells in CB compared to later in life, implying an importance of innate immunity in early life before the adaptive immune system matures. Additionally, we found that the proportion of LIR‐1+ NK cells increased with increasing age while CD94+NKG2C− (NKG2A+) NK cells and the level of expression of NKG2D, NKp30 and NKp46 decreased with age. These age related changes in NK cell populations defined by the expression of activating and inhibitory receptors may be the result of pathogen exposure and/or a continuation of the maturation process that begins in the bone marrow.

Influence of atopic heredity on IL-4-, IL-12- and IFN-γ-producing cells in in vitro activated cord blood mononuclear cells

Several reports have claimed that there is a greater risk for a child with an atopic mother to develop allergy as compared to a child with an atopic father. This suggests that the fetal environment during pregnancy might be of importance for the development of atopic disease. Both proliferative and cytokine responses have been detected in cord blood mononuclear cells (CBMC) after stimulation with allergens, suggesting allergen priming already in utero. The aim of this study was to investigate whether the atopic status of the mother influences cytokine production by CBMC. We compared interleukin (IL)‐4, IL‐12 and interferon (IFN)‐γ‐producing CBMC from children with double atopic heredity (dh), maternal atopic heredity only (mh) or no atopic heredity (nh). CBMC were stimulated in vitro with allergens (birch, ovalbumin and cat), phytohaemagglutinin (PHA) or purified protein derivative (PPD) and cytokine‐producing cells were measured by the enzyme‐linked immunospot assay. In response to PHA, the frequency of IL‐4‐producing cells, as well as the ratio of IL‐4/IFN‐γ‐producing cells, were significantly higher in the dh group compared to the nh group. High numbers of IL‐12‐producing cells in response to allergens were detected, significantly highest in the nh group, followed by the dh and mh groups. Our results suggest that there is a stronger Th2 bias after in vitro stimulation of CBMC from children with atopic heredity, as reflected by higher IL‐4/IFN‐γ ratios in response to PHA, and lower numbers of IL‐12‐producing cells after allergen stimulation. Whether these differences influence later allergy development will be evaluated when the atopic status of the children is assessed at 2 years of age.