Marija Gavrovic-Jankulovic

Immediate allergic reactions to cephalosporins and penicillins and their cross‐reactivity in children

Penicillins and cephalosporins are the most important betalactams inducing IgE‐mediated reactions. The safety of administering cephalosporins to penicillin‐allergic children is a particular problem, because cephalosporin allergenic determinants have not been properly identified. A study was undertaken to evaluate the frequency of anaphylactic reactions to cephalosporins and penicillins and their cross‐reactivity in a pediatric population. A prospective survey was conducted in a group of 1170 children with suspected immediate allergic reactions to cephalosporins and/or penicillins, which were examined during a period of 8 yr. In vivo (skin tests and challenges) and in vitro tests (for specific IgE) were performed with standard concentration of penicillins and cephalosporins. When 1170 children with a clinical history of allergy to penicillins and/or cephalosporins were tested in vivo for immediate hypersensitivity to betalactams, 58.3% cases overall were found to be skin or challenge test positive. Among them, 94.4% patients were positive to penicillins and 35.3% to cephalosporins. The frequency of positive reactions in the in vivo testing was in the range from 36.4% to 88.1% for penicillins and from 0.3% to 29.2% for cephalosporins. However, 31.5% of the penicillin allergic children cross‐reacted to some cephalosporin. If a child was allergic to a cephalosporin, the frequency of positive reactions to penicillin was 84.2%. The cross‐reactivity between cephalosporins and penicillins varied between 0.3% and 23.9%. The cross‐reactivity among different generations of cephalosporins varied between 0% and 68.8%, being the highest for first and second‐generation cephalosporins and 0% for third generation cephalosporins. The frequency of immediate allergic reactions to cephalosporins is considerably lower compared to penicillins, and the degree of cross‐reactivity between cephalosporins and penicillins depends on the generation of cephalosporins, being higher with earlier generation cephalosporins. The cross‐reactivity among cephalosporins is lower compared to cross‐reactivity between penicillins and cephalosporins.

A matrix effect in pectin-rich fruits hampers digestion of allergen by pepsin in vivo and in vitro

Background It is a general belief that a food allergen should be stable to gastric digestion. Various acidic plant polysaccharides, including pectin, are ubiquitous in fruit matrixes and can form hydrogels under low‐pH conditions.

Allergenic potency of kiwi fruit during fruit development

Abstract Food allergies, including kiwi fruit allergy, have been the subject of extensive research in the last few years. The aim of this study was to examine a possible relationship between the developmental stage of kiwi fruit and its allergenic potency. The protein and allergen patterns of kiwi fruit extracts in September, October, November and December fruit in the period from 2000–2002 were analysed. One of the factors that may contribute to the difficulties in proposing well-defined and standardized fruit extracts should also be the time of fruit harvesting. In this particular case, when the kiwi fruit was edible throughout November and December, we showed discrepancies in allergen content and potencies both in qualitative and quantitative terms. Two major allergens of kiwi fruit, Act c 1 and Act c 2, mainly accounted for the highest allergenic potential of November kiwi extract in vivo and in vitro. Not only the content of major allergens, but also the ratio of different proteins and even isoforms of the same allergen (Act c 2) change with fruit ripening. These findings should be taken into account during preparation of extracts for allergy diagnosis.

Non‐immediate hypersensitivity reactions to beta‐lactam antibiotics in children – our 10‐year experience in allergy work‐up

Non‐immediate reactions to beta‐lactam antibiotics (BL) occur more than one hour after drug administration, and the most common manifestations are maculopapular exanthemas and delayed‐appearing urticaria and/or angioedema. Infections can lead to skin eruptions and mimic drug hypersensitivity reactions (DHR), if a drug is taken at the same time. The most of children are labeled as ‘drug allergic’ after considering only the clinical history.

Evaluation of IgE reactivity of active and thermally inactivated actinidin, a biomarker of kiwifruit allergy

Actinidin, an abundant cysteine protease from kiwifruit, is a specific biomarker of isolated allergy to kiwifruit. This study evaluates the IgE-binding properties of biologically active and thermally inactivated actinidin. Employing two different activity assays (caseinolytic assay and zymogram with gelatin) we showed that actinidin obtained from kiwifruit extract under native conditions represents a mixture of inactive and active enzyme. The structural integrity of actinidin was confirmed by SDS-PAGE, Edman degradation, mass fingerprint and Western blot with polyclonal antibodies. Although it was capable of inducing positive skin prick test reactions, we failed to detect IgE reactivity of active actinidin in Western blot with patient sera. Thermally inactivated actinidin exhibited IgE reactivity both in vivo and in vitro, indicating that heat processed kiwifruit products may induce clinical reactivity. These findings imply that apart from the allergenic epitopes on its surface, actinidin also contains hidden epitopes inside the protein which become accessible to IgE upon thermal treatment.

The influence of a residual group in low-molecular-weight allergoids of Artemisia vulgaris pollen on their allergenicity, IgE- and IgG-binding properties

Background: Reaction of ε‐amino groups of lysine with potassium cyanate, maleic, or succinic anhydride leads to allergoids of low molecular weight. No study has been performed to compare their properties and investigate the influence of a residual group on allergenicity and human IgE‐ and IgG‐binding of these derivatives.

The identification of a low molecular mass bacteriocin, rhamnosin A, produced by Lactobacillus rhamnosus strain 68.

Aims:  This study focuses on the isolation and characterization of a peptide with bacteriocin‐like properties isolated from Lactobacillus rhamnosus strain 68, previously identified by 16S rRNA gene sequencing and originating from human gastrointestinal flora.

Quantification of the thaumatin-like kiwi allergen by a monoclonal antibody-based ELISA

Thaumatin-like proteins (TLPs) have been established as a new family of fruit and pollen allergens. The aim of this study was to develop a two-site ELISA for the quantification of the thaumatin-like kiwi allergen (Act d 2) in kiwifruit extracts and kiwifruit-containing food products. Genomic DNA (gDNA) of Act d 2 was amplified and the deduced amino acid sequence was determined to obtain a primary structure. Act d 2 purified from kiwifruit extract by HPLC was identified by Edman degradation and MS. Balb/c mice were immunized with Act d 2 for the production of mAbs by hybridoma technology. The optimized ELISA measured Act d 2 concentrations ranging from 0.2 to 9.0 ng/mL, with intra- and interassay coefficients of variation of 3.65 and 10.44%, respectively. The developed ELISA is a useful method for the quantification of the thaumatin-like kiwi allergen in kiwifruit extracts as well as the allergen level in kiwifruit-containing food products. It may be a helpful analytical tool for the evaluation of the stability (integrity) of fruit allergen extracts for in vitro diagnosis.

Stevens–Johnson syndrome and toxic epidermal necrolysis in children

Stevens–Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) are the most severe forms of hypersensitivity reactions affecting the skin. Current terminology is based on maximal extent of epidermal detachment. SJS indicates cases with epidermal necrolysis that involve less than 10% of the body surface area, TEN with more than 30%, and overlap of SJS/TEN in between (1). Clinically, SJS/TEN are characterized by polymorphic lesions like erythematous macules, papules, plaque, vesicles, and bullae with Nikolsky’s sign positive. Oral, genital, and conjunctival mucosae are often involved in the form of erosion or ulceration (2). Fever and malaise are the first symptoms of the disease (3). Incidence of SJS/TEN is 0.05–3 persons per million populations per year (2, 4). Several drugs are highly suspected to cause SJS/TEN in adults, such as anti-epileptics, anti-infective sulfonamides, nonsteroidal anti-inflammatory drugs, nevirapin, allopurinol, and antimicrobials (cephalosporins, aminopenicillins, quinolones, tetracyclines, and imidazole antifungals) (4–12). The list of causative drugs may vary from country to country (4). In children, anti-infective sulfonamides, phenobarbital, carbamazepine, lamotrigine, and acetaminophen are frequently associated with SJS/TEN (12). However, SJS/TEN are rare in children with mortality rate of 7.5% (12). In this article, evaluation of children with SJS/TEN, investigation of causative drug/drugs, treatment, clinical outcome, and complications are presented in three cases.

Diagnosing multiple drug hypersensitivity in children

Multiple drug hypersensitivity (MDH) has been defined as a hypersensitivity to two or more chemically different drugs. Two types of MDH have been reported: the first one, which develops to different drugs administered simultaneously and the second type, in which sensitizations develop sequentially. In children, studies which diagnose MDH on the basis of positive allergologic tests to 2 or more chemically different drugs are lacking.