Elena Laffond

Interleukin-4 (IL4) and Interleukin-4 receptor (IL4RA) polymorphisms in asthma: a case control study

BackgroundIL4/IL4RA pathway plays an important role in atopy and asthma. Different polymorphisms in IL4 and IL4RA genes have been described. Particularly, -33C>TIL4 and 576Q>RIL4RA SNPs have been independently associated to atopy and asthma. The purpose of this study was to analyse these polymorphisms in a population of patients with a well-characterized asthma phenotype.MethodsA total of 212 unrelated Caucasian individuals, 133 patients with asthma and 79 healthy subjects without symptoms or history of asthma or atopy and with negative skin prick tests were recruited. Lung function was measured by spirometry and asthma was specialist physician-diagnosed according to the ATS (American Thoracic Society) criteria and classified following the GINA (Global Initiative for Asthma) guidelines. Skin prick tests were performed according to EAACI recommendations. -33C>TIL4 was studied with TaqMan assay and 576Q>RIL4RA by PCR-RFLP technique. Hardy-Weinberg equilibrium was analysed in all groups. Dichotomous variables were analysed using χ2, Fisher exact test, Monte Carlo simulation test and odds ratio test. To model the effects of multiple covariates logistic regression was used.ResultsNo statistically significant differences between the group of patients with asthma and the controls were found when the allele and genotype distribution of -33C>TIL4 and 576Q>RIL4RA polymorphisms were compared. However, the T allele of the -33C>TIL4 SNP was more frequent in patients with persistent asthma. Multivariate analysis adjusted for age and sex confirmed that carriers of allele T had an increased risk of persistent asthma (OR:2.77, 95%CI:1.18–6.49; p = 0.019). Analysis of combination of polymorphisms showed that patients carrying both the T allele of -33C>TIL4 and the A allele of 576Q>RIL4RA had an increased risk of asthma. This association was particularly observed in persistent asthma [Fishers p value = 0.0021, Monte Carlo p value (after 104 simulations) = 0.0016, OR:3.39; 95% CI:1.50–7.66].ConclusionOur results show a trend of association between the genetic combination of the T allele of -33C>TIL4 and the A allele of 576Q>RIL4RA with asthma. This genetic variant was more frequently observed in patients with persistent asthma. As long as this study was performed in a small population, further studies in other populations are needed to confirm these results.

Hypersensitivity reactions to cephalosporins

At present, cephalosporins represent one of the most prescribed classes of antibiotics. Although allergic reactions have been estimated to be infrequent, the number of reactions to cephalosporins is increasing due to their wide use. Cross-reactivity with penicillins has mainly been evaluated in patients with penicillin allergy. It is higher between first- and second-generation cephalosporins with the same or similar side chain than between cephalosporins with different side chains. Unlike penicillins, cephalosporin haptens or determinants have not been defined, and therefore the diagnosis is complicated. Nevertheless, skin tests with cephalosporins are useful in the evaluation of several allergic reactions. Although more studies are necessary, a negative result in skin testing to penicillin and cephalosporins with different side chains seems to be a good predictor of tolerance, and could be used in select cases.

Promoter genetic variants of prostanoid DP receptor (PTGDR) gene in patients with asthma

Background:  PTGDR gene has been identified as an asthma‐susceptibility gene. Recently, functional genetic variants have been associated with asthma. The objective of this work was to study −549T>C, −441C>T and −197T>C PTGDR promoter polymorphisms in a Spanish population.

927T>C polymorphism of the cysteinyl-leukotriene type-1 receptor (CYSLTR1) gene in children with asthma and atopic dermatitis.

Asthma and atopic dermatitis share several common features and Cysteinyl‐leukotrienes are mediators that participate in the pathogenesis of both diseases. Recently, a new polymorphism (927T>C) has been identified in cysteinyl‐leukotriene type‐1 receptor (CYSLTR1) gene. This gene is found on the X chromosome. The aim of this study was to analyze this SNP in a population of children with asthma and atopic dermatitis. In this study, 166 individuals, 79 adult controls (CTR) and 87 children with asthma (AA) were included. Forty‐one patients with asthma presented atopic dermatitis (AA‐AD). Adults were chosen as controls to confirm lack of development of asthma and allergy during childhood. Standardized history, physical examination, skin prick tests, and lung function measurements were performed in all patients. The 927T>C CYSLTR1 SNP was analyzed by direct sequencing after PCR amplification. In males (53 individuals), the C allele was significantly more common among AA‐AD patients (47%) than in CTR (8%) (Fishers p < 0.005; Monte Carlo p < 0.008; OR:9.78; 95%CI: 1.73–55.30). When comparing AA‐AD vs. AA‐NAD (patients with asthma but not atopic dermatitis), significant differences were observed, (47% vs. 15%, Fishers p = 0.014; Monte Carlo p = 0.022; OR: 4.97; 95%CI: 1.29–19.13). No differences in allele distribution were observed between these disease sub‐groups in females. The 927T>C is a silent SNP; however, it could affect transcription or translation or may be linked to an unidentified, functional polymorphism and thus may pre‐dispose male children to asthma and atopic dermatitis in our population. Further studies are needed to confirm these findings.

Usefulness of intradermal test and patch test in the diagnosis of nonimmediate reactions to metamizol

Background:  Metamizole is a pyrazolone derivative, and its most common reactions are IgE‐mediated reaction and idiosyncratic reactions. Non‐immediate reactions are poorly described and there are very few reports on non‐immediate reactions to pyrazolones.

El polimorfismo Q576R del gen IL4RA se asocia con valores elevados de IgE total en pacientes con antecedentes familiares de atopia

Fundamento y objetivo: La atopia es un proceso de base inmunologica que comprende la dermatitis atopica y la rinitis y el asma alergicas. Se ha descrito una asociacion entre la atopia y el polimorfismo Q576R del gen IL4RA. El objetivo de este estudio es analizar este polimorfismo en una poblacion de pacientes atopicos y no atopicos, y su posible relacion con los valores de IgE y con los antecedentes familiares de atopia. Pacientes y metodo: El polimorfismo Q576R se analizo mediante RFLP en 154 pacientes del Servicio de Alergia del Hospital Universitario de Salamanca. Resultados: No se encuentra asociacion entre el alelo R576 y la presencia de atopia ni con los valores de IgE. Sin embargo, se ha detectado una asociacion entre este alelo y los valores mas elevados de IgE en los pacientes con pruebas cutaneas positivas y antecedentes familiares de atopia. Conclusiones: El alelo R576 podria caracterizar un grupo de pacientes con antecedentes familiares de atopia, en los cuales la presencia de este alelo podria estar relacionada con valores de IgE total mas elevados

Performance in real life of the European Network on Drug Allergy algorithm in immediate reactions to beta-lactam antibiotics.

European Network on Drug Allergy (ENDA) has proposed an algorithm for diagnosing immediate beta‐lactam (BL) allergy. We evaluated its performance in real life. During 1994–2014, 1779 patients with suspected immediate reactions to BL were evaluated following ENDAs short diagnostic algorithm. Five hundred and nine patients (28.6%) were diagnosed of BL hypersensitivity. Of them, 457 (25.7%) were at first evaluation [403 by skin tests (ST), 12 by positive IgE and 42 by controlled provocation tests (CPT)]. At second evaluation (SE), 52 additional patients (10.2% of allergic patients) were diagnosed, [50 (2.8%) by ST and 2 (0.1%) by CPT]. Time between reaction and study was significantly longer in patients diagnosed at SE (median 5 vs 42 months; IQR 34 vs 170; P < 0.0001). Anaphylaxis was significantly associated with a diagnosis at SE. European Network on Drug Allergy/EAACI protocol was appropriate and safe when evaluating BL immediate reactions. Re‐evaluation should be performed, particularly when anaphylaxis and long interval to diagnosis are present.

Molecular Analysis of Activation-Induced Cytidine Deaminase Gene in Immunoglobulin-E Deficient Patients

Understanding how class switch recombination (CSR) is regulated to produce immunoglobulin E (IgE) has become fundamental because of the dramatic increase in the prevalence of IgE-mediated hypersensitivity reactions. CSR requires the induction of the enzyme AICDA in B cells. Mutations in AICDA have been linked to Hyper-IgM syndrome (HIGM2), which shows absence of switching to IgE as well as to IgG and IgA. Although isolated IgE deficiency is a rare entity, here we show some individuals with normal serum IgM, IgG, and IgA levels that had undetectable total serum IgE levels. We have analyzed the AICDA gene in these individuals to determine if there are mutations in AICDA that could lead to selective IgE deficiency. Conformational sensitive gel electrophoresis (CSGE) and sequencing analysis of AICDA coding sequences demonstrated sequence heterogeneity due to 5923A/G and 7888C/T polymorphisms, but did not reveal any novel mutation that might explain the selective IgE deficit.

Resolution of Type IV Hypersensitivity After Bone Marrow Transplantation

Transfer of autoimmune, IgE-mediated type IV hypersensitivity has been reported after bone marrow transplantation [1-3]. Nevertheless, remission of allergic diseases after bone marrow transplantation has rarely been described [4]. We report a case of allergic contact dermatitis (ACD) that resolved after allogeneic hematopoietic stem cell transplantation (HSCT). In 2006, a 41-year-old woman with acute myeloid leukemia (M5 subtype) underwent HSCT from an HLA-matched donor with a conditioning regimen based on thymoglobulin and cyclophosphamide. The patient achieved complete chimerism after the transplant. Since she had previously developed severe eczema upon contact with metallic earrings or watches, she avoided contact with such objects. No patch tests were performed before HSCT. After HSCT, she observed that she no longer developed lesions upon contact with the same metal objects that had previously produced the eczematous lesions. Patch testing with a standard battery of contact allergens including nickel, cobalt, and chrome (T.R.U.E. TEST, SmartPractice Denmark ApS) was negative at D2-D4. During an 8-year follow-up period, she did not develop eczema despite regular use of costume jewelry. We present a case of resolution of ACD after HSCT. Our findings are limited by the absence of patch testing before HSCT and by the fact that the diagnosis of nickel allergy was based on a very highly suggestive clinical history. Nevertheless, the clinical picture points to resolution of nickel ACD, as the patient was able to wear metallic costume jewelry several months after transplantation. Resolution of type I hypersensitivity disease has been infrequently described [4], although, to our knowledge, the disappearance of type IV hypersensitivity has not been reported. A possible underlying mechanism of resolution could be the replacement of recipient hematolymphoid cells by nonallergic donor cells. In addition, immunosuppressive therapy (cyclosporine A) could have accounted for resolution, although this mechanism did not seem to be involved, as the patient had not developed metal-induced contact dermatitis during the 8 years after discontinuation of immunosuppressive therapy. Another possibility could be spontaneous remission of nickel allergy, although this is extremely infrequent. Thus, Patriarca et al [5] observed that immediate positive skin tests to ß-lactams became negative in 58.3% of type I allergic patients, but only in 6.7% of those with positive ß-lactam patch test results. To further clarify this point, more allergic patients receiving BMT from nonallergic donors and controls should be studied. In conclusion, we report a case of resolution of type IV hypersensitivity after bone marrow transplantation.

Tolerability of iobitridol in patients with non-immediate hypersensitivity reactions to iodinated contrast media

Youngwoo Choi Dong-Hyun Lee Ji-Ho Lee Yoo Seob Shin Seung-Hyun Kim Hae-Sim Park Department of Allergy and Clinical Immunology, Ajou University School of Medicine, Suwon, Korea Clinical Trial Center, Ajou University Medical Center, Suwon, Korea Correspondence: Hae-Sim Park, Department of Allergy and Clinical Immunology, Ajou University School of Medicine, 164 World cup-ro, Yeongtong-gu, Suwon, Korea (hspark@ajou.ac.kr).