Robert Movérare

Measurement of Ara h 1‐, 2‐, and 3‐specific IgE antibodies is useful in diagnosis of peanut allergy in Japanese children

To cite this article: Ebisawa M, Movérare R, Sato S, Maruyama N, Borres MP, Komata T. Measurement of Ara h 1‐, 2‐, and 3‐specific IgE antibodies is useful in diagnosis of peanut allergy in Japanese children. Pediatr Allergy Immunol 2012: 23: 573–581.

The usefulness of casein-specific IgE and IgG4 antibodies in cow's milk allergic children.

BackgroundCows milk allergy is one of the most common food allergies among younger children. We investigated IgE antibodies to milk, and IgE and IgG4 antibodies to casein, α-lactalbumin and β-lactoglobulin in cows milk allergic (CMA) and non-allergic (non-CMA) children in order to study their clinical usefulness.MethodsEighty-three children with suspected milk allergy (median age: 3.5 years, range: 0.8-15.8 years) were diagnosed as CMA (n = 61) or non-CMA (n = 22) based on an open milk challenge or convincing clinical history. Their serum concentrations of allergen-specific (s) IgE and IgG4 antibodies were measured using ImmunoCAP®. For the sIgG4 analysis, 28 atopic and 31 non-atopic control children were additionally included (all non-milk sensitized).ResultsThe CMA group had significantly higher levels of milk-, casein- and β-lactoglobulin-sIgE antibodies as compared to the non-CMA group. The casein test showed the best discriminating performance with a clinical decision point of 6.6 kUA/L corresponding to 100% specificity. All but one of the CMA children aged > 5 years had casein-sIgE levels > 6.6 kUA/L. The non-CMA group had significantly higher sIgG4 levels against all three milk allergens compared to the CMA group. This was most pronounced for casein-sIgG4 in non-CMA children without history of previous milk allergy. These children had significantly higher casein-sIgG4 levels compared to any other group, including the non-milk sensitized control children.ConclusionsHigh levels of casein-sIgE antibodies are strongly associated with milk allergy in children and might be associated with prolonged allergy. Elevated casein-sIgG4 levels in milk-sensitized individuals on normal diet indicate a modified Th2 response. However, the protective role of IgG4 antibodies in milk allergy is unclear.

Monitoring Ara h 1, 2 and 3-sIgE and sIgG4 antibodies in peanut allergic children receiving oral rush immunotherapy

The aim was to study the clinical efficacy and safety of rush oral immunotherapy (OIT) for severe peanut‐allergic children and to measure the antibody responses.

Characterization of anti-natalizumab antibodies in multiple sclerosis patients

Background: A small proportion of multiple sclerosis (MS) patients treated with natalizumab develop anti-drug antibodies. Objective: The objective of this paper is to characterize the anti-natalizumab antibody response and to investigate differences between persistently and transiently antibody-positive patients. Methods: Screening for anti-natalizumab antibodies was performed using a standardized bridging ELISA. Antibody-positive samples were further analyzed for IgM and IgG1–4 antibodies using ELISA and ImmunoCAP®. Results: Anti-natalizumab antibodies developed in 57 of 1379 (4.1%) treated patients after a median treatment duration of three months. Of the positive patients, 20 (35%) patients reverted to negative, 19 (33%) patients were confirmed persistently positive and 18 (32%) patients were unconfirmed positive. Significantly higher anti-natalizumab antibody levels were detected in persistently compared to transiently positive patients. A cutoff value predicting persistence of antibodies could be determined with a sensitivity of 0.84 and a specificity of 0.80. IgM and IgG4 antibody levels were significantly higher in persistently compared to transiently positive patients, and IgG1, IgG2 and IgG4 increased significantly over time. Conclusions: The level of total anti-natalizumab antibodies in a first positive sample can be used to predict patients at risk for persisting antibody positivity. However, neither IgM nor IgG1–4 antibodies could be used to discriminate between transiently and persistently positive patients.

High IgE levels to α‐lactalbumin, β‐lactoglobulin and casein predict less successful cow's milk oral immunotherapy

A new treatment option for persistent cows milk allergy (CMA) is oral immunotherapy (OIT). Not all patients develop tolerance during therapy, and markers to identify those who will benefit from it are needed. The objective was to study the IgE and IgG4 antibody profiles to milk and milk proteins before and after OIT in relation to clinical outcome.

Measurement of specific IgE antibodies to Ses i 1 improves the diagnosis of sesame allergy

The number of reported cases of allergic reactions to sesame seeds (Sesamum indicum) has increased significantly. The specific IgE tests and skin prick tests presently available for diagnosis of sesame allergy are all based on crude sesame extract and are limited by their low clinical specificity. Thus, oral food challenge (OFC) is still the gold standard in the diagnosis.

The predictive relationship between peanut- and Ara h 2–specific serum IgE concentrations and peanut allergy

The predictive relationship between peanut- and Ara h 2-specific serum IgE concentrations and peanut allergy

IgG4 antibodies and peanut challenge outcome in children IgE-sensitized to peanut

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Jug r 1 sensitization is important in walnut-allergic children and youth

Tree nut allergies have become a public health problem over the past 2 decades and managing nut allergies is a remaining clinical challenge. Walnut (Juglans regia) is the most prevalent eaten tree nut in Japan and is the most common tree nut causing anaphylaxis. If an allergy to tree nut is suspected, guidance for food removal is often given without any oral food challenge (OFC) being performed due to the high risk of anaphylaxis. IgE measurement to nut allergen components has been shown to increase the clinical specificity compared with measuring IgE to whole nut extract. However, the only walnut component study in children presented so far was a retrospective study based on doctor’s diagnosis without obligatory OFC. The aim of the present study was to investigate the predictive value of measuring IgE to walnut and the walnut components Jug r 1 (2S albumin, storage protein) and Jug r 3 (nonspecific lipid transfer protein [nsLTP]) in Japanese children and youth suspected of walnut allergy in comparison with the results of OFC. One-hundred and eight patients with suspected walnut allergy, who had a history of immediate reaction to walnut or sensitized to walnut, were enrolled in the study. All patients were defined as allergic or tolerant to walnut based on an OFC outcome (Table I). A majority of the patients had atopic dermatitis (59%) and suffered from other food allergies (70%), and 33% had an asthma diagnosis (Table I). Forty-two children (39%) had a history of reported allergic reaction to walnut. OFC was conducted according to the Japanese Food Allergy Guidelines and is described in this article’s Online Repository at www. jaci-inpractice.org. Ethics approvals were obtained from the institutional review boards of the participating hospitals. Informed consent was obtained from all children and/or their parents. Detailed statistic method descriptions are presented in this article’s Online Repository. The cumulative dose of walnut resulting in objective allergic symptoms during OFC varied from 0.1 to 10 g (median dose, 3 g). Skin reactions were the most commonly observed symptoms during OFC (71%) and 6 children had moderate oral allergy syndrome (OAS) as the only symptom. More than half of subjects had respiratory symptoms due to the challenge. Two patients had anaphylactic shock and were successfully treated. The clinical efficacy of measuring IgE antibodies to walnut, Jug r 1, and Jug r 3 was evaluated using the ImmunoCAP technology (Thermo Fisher Scientific/Phadia AB, Uppsala, Sweden). The sIgE levels to walnut were significantly higher in the allergic group when compared with the tolerant group (Table I). This was also true for Jug r 1, but not for Jug r 3. There was a nonsignificant trend that children with anaphylactic shock or lower respiratory symptoms during challenge had higher sIgE levels to Jug r 1 (n 1⁄4 31; 6.76 kUA/L, range: <0.1->100 kUA/L) than allergic children with moderate OAS, skin, digestive, or upper respiratory symptoms (n 1⁄4 29; 2.15 kUA/L, range: <0.1-37.6 kUA/L, P < .10). Receiver operating characteristic (ROC) analysis showed that the Jug r 1 ImmunoCAP test had the largest area under the curve (0.843; 95% confidence interval [CI], 0.574-0.854) compared with the walnut test (0.792; 95% CI, 0.418-0.711) (Figure 1). Using the statistically optimal cutoff for sIgE to Jug r 1 (0.42 kUA/L), determined from the ROC analysis, a clinical sensitivity and specificity of 85% and 79% was obtained, respectively (Table E1, available in this article’s Online Repository at www. jaci-inpractice.org). Thus, 19 children (18%) would have been misclassified using the cutoff of 0.42 kUA/L. The walnut ImmunoCAP test had both a lower clinical sensitivity (73%) and specificity (70%) at the optimal cutoff (2.6 kUA/L), and 30 of the 106 children tested (28%) would then have been misclassified. By using the traditional 0.35 kUA/L cutoff, a sensitivity of 98% was obtained for the walnut test compared with 88% for Jug r 1. The corresponding specificities in this study population was 77% for Jug r 1 and only 17% for walnut. We show in this study that measuring sIgE to Jug r 1 increases the specificity of the diagnosis of walnut allergy compared with using complete walnut extract. This is aligned with other nut studies examining the clinical utility of sIgE testing to storage protein, for example, hazelnut, walnut, cashew and pistachio, and peanut. However, in a Dutch study by Blankestijn et al, IgE testing to Jug r 1 had no additional value compared with sIgE to walnut in diagnosing walnut allergy in adults. Masthoff et al observed that adult hazelnut-allergic patients had less sensitization to 2S albumin from hazelnut than children, indicating an age-related association. An explanation to their and our findings could be that tree pollen-related sensitization becomes a more frequent cause of nut allergy through adolescence and early adulthood. Only 24% of our subjects had allergic rhinitis compared with 86% in the Dutch walnut study, which supports this hypothesis. In addition, Jug r 1 is obviously not the only relevant walnut component. Other storage proteins besides Jug r 1 might also be of importance. The negative association between sIgE to Jug r 3 and walnut allergy observed in our study might be attributed to a primary sensitization to other highly cross-reactive nsLTPs in pollen or fruits, obviously with limited impact on tree nut allergy in the present population. Despite the low prevalence, walnut allergy is one of the leading causes of food anaphylaxis. A high prevalence of respiratory symptoms in walnutand pecan-allergic subjects was also observed by Maloney et al. We also observed that more than half of subjects who failed OFC reacted with respiratory symptoms

IgG4 anti-infliximab in treated patients: Clinical impact and temporal evolution

Infliximab (IFX) carries potential risk of immunogenicity with the production of anti‐drug antibodies (ADA). ADA may belong to different isotypes and are usually measured by ELISA bridging assay. This test is not designed to detect IgG4 antibodies. The aim was to measure IgG4 anti‐IFX antibodies in a cohort of IFX‐treated patients and to evaluate their relationship with ADA and their clinical impact.