Background Cross-reactive carbohydrate determinants (CCDs) in plants and insect venoms are a common cause of irrelevant positive test results during in vitro allergy diagnosis. We observed that some ...CCD-positive sera show nonspecific IgE binding even with CCD-free recombinant allergens when using the Phadia ImmunoCAP platform. Objective We investigated whether cellulose used as an allergen carrier in ImmunoCAP harbors residual N-glycans, causing nonspecific background binding in CCD-positive sera. Methods IgE binding to 6 samples of blank ImmunoCAPs coupled to either streptavidin (SA-CAP-1 or 2) or nonallergenic maltose-binding protein (MBP; MBP-CAP-1 to 4) and binding to a panel of 4 recombinant allergens were compared in CCD-positive sera before and after inhibition with a CCD inhibitor (MUXF3 –human serum albumin). Results Of 52 CCD-positive sera (bromelain, 1.01-59.6 kilounits of antigen per liter kUA /L) tested on SA-CAP-1, 35 (67%) showed IgE binding of greater than 0.35 kUA /L (0.41-4.22 kUA /L). Among those with anti-CCD IgE levels of greater than 7.0 kUA /L, 90% (26/29) were positive. IgE binding to SA-CAP-1 correlated with IgE binding to bromelain ( r = 0.68) and was completely abolished by serum preincubation with the CCD inhibitor (n = 15). Binding scores with SA-CAP-2 and MBP-CAP-1 to MBP-CAP-4 were generally lower but strongly correlated with those of SA-CAP-1 and bromelain. IgE reactivity of 10 CCD-positive sera (14.0-52.5 kUA /L) with the recombinant allergens rPhl p 12, rFel d 1, rAra h 2, and rPru p 3 was positive to at least 1 allergen in 8 of 10 (0.36-1.63 kUA /L) and borderline in 2 of 10 (0.21-0.25 kUA /L). Binding correlated with antibody binding to bromelain ( r = 0.61) and to all blank ImmunoCAPs ( r > 0.90) and could be completely blocked by the CCD inhibitor. Overall, mean background binding to cellulose CCDs corresponded to 2% to 3% of the reactivity seen with bromelain. Conclusions Cellulose used as a solid-phase allergen carrier can contain varying amounts of CCDs sufficient to cause false-positive test results up to 2 kUA /L with nonglycosylated recombinant allergens in patients with high levels of anti-CCD IgE antibodies.
Many patients report questionable drug hypersensitivity reactions (DHR) to betalactam antibiotics. A workup is required for objectivation. Direct drug provocation tests (DPTs) omitting a prior ...allergy workup are increasingly recommended as the primary diagnostic approach. However, apart from the risk of severe side effects, DPTs often are a scarce resource in overloaded healthcare-systems. We investigated how many cases can be solved by drug-specific history, drug-specific IgE, and skin tests obviating the need for DPT.
We conducted a chart review in a retrospective cohort of 932 patients in an allergy outpatient centre from 2016 to 2017. Patients had been submitted to drug-specific history and specific IgE-, skin prick-, intradermal- and patch-tests with early and late readings with a series of penicillins and cephalosporins but DPTs were no option.
Overall, positive in vitro and/or skin tests were found in 96/932 (10.3%) patients. Drug-specific IgE was detected in 40/932 (4.3%) patients, 61/787 (7.8%) patients had positive skin tests. In vitro tests to Pencillin V showed the highest rate of positivity 24/479 (5.0%) and early readings of ampicillin the highest amongst the skin tests (3/49, 6.1%). Immediate skin tests were more often positive than delayed ones (75:45). The combination of all parameters including drug-specific history solved 346/932 (37.1%) cases while 586/932 (62.9%) remained unresolved. Self-reported DHR could be less often confirmed in females and young children (p < 0.05).
Testing with betalactams applying simple, cheap, and safe skin and blood tests can solve a third of DHR-cases on a high throughput scale.
Summary
This statement was written by a group of pulmonologists and pediatric pulmonologists belonging to the corresponding professional associations ÖGP (Austrian Society for Pulmonology) and ÖGKJ ...(Austrian Society for pediatric and adolescent medicine) to provide a concise overview of the latest updates in the 2015 GINA Guidelines and to include aspects that are specific to Austria.
Allergic diseases affect approximately one-quarter to one-half of the average population under 50 years of age in Central Europe. Due to the high proportion of affected individuals, allergy testing ...needs to be performed on a large scale, with high sensitivity and specificity at a low cost. Skin tests are the most important diagnostic measure fulfilling these requirements: they can be performed immediately and, quite in contrast to laboratory tests, the results of skin prick tests for the diagnosis of immediate allergy (IgE-mediated: Type I) can be assessed, and discussed with the patients 15–20 minutes later. Patients do not need to be called in for a second appointment to discuss the results of serum-based determination of specific IgE. Recently, we demonstrated that the sensitivity of skin prick tests is superior to the measurement of allergen-specific IgE, even for modern molecular allergens. In T cell mediated allergy of the delayed type (contact dermatitis: Type IV), patch tests read after 48–72 hours are the only available diagnostic measure.
Background
As extract‐based skin testing as well as in vitro tests for major allergens have their own advantages, both procedures are usually performed in routine settings. In times of shortages in ...medical staff and supplies, we asked ourselves, how many patients would be underdiagnosed, if only one test could be used.
Methods
In a retrospective analysis, we investigated a cohort of 2646 patients seen by a single physician in a large Austrian outpatient allergy clinic in 2018. Only patients with an allergen source‐specific history and pairs of extract‐based skin prick (SPT) and in vitro molecular allergy tests to major allergens were included.
Results
For all tested allergen sources, sensitivity was higher for SPT than for sIgE‐based molecular allergy testing. Concerning 1006 birch pollen‐allergic patients, 791 (78.6%) had positive results with both tests, while 153 (15.2%) only with the SPT and 62 (6.2%) only with the sIgE to Bet v1. The other allergen sources showed similar results: For house dust mite 816/1120 (72.9%), grass pollen 1077/1416 (76.1%) and cat 433/622 (69.6%) remained test‐positive with both procedures, whereas in 276 (24.6%), 224 (15.8%) and 173 (27.8%) times only the SPT and 28 (2.5%), 115 (8.1%) and 16 (2.6%) times only the sIgE to Der p1/2/23, Phl p1/5 and Fel d1 showed a positive result. Each comparison was statistically significant (each p < 0.0001, Chi‐squared test).
Conclusions
Screening for allergy with major molecular allergens has lower sensitivity when compared with extract‐based skin tests. A combination of both is required for an optimal sensitivity.
Dear Editor, Millets encompass a group of cereals from the Poaceae family botanically related to wheat, corn (maize) and rice. While a basic foodstuff in many developing countries, millet is consumed ...in Westernized countries rather as a "healthy" alternative cereal or a gluten-free substitute for wheat. Yet, millet allergy has been mainly recognized in industrialized countries rather than in low-income countries with high millet consumption, because sensitization seems to occur mostly via the respiratory route through millet-containing birdseed in pet bird holders. Until now only a very limited number of cases have been described from the USA, Japan and Central Europe, many of them involving severe anaphylaxis. Millet allergens have not yet been identified in detail and data concerning their potential cross-reactivity with homolog allergens in other cereals are controversial. Between 2003 and 2015 we identified nine adult patients with a convincing history of millet allergy. Demographic characteristics, clinical symptoms and potential bird exposure are summarized in Table 1. All patients reacted to millet at the very first occasion.
Methods We studied IgE binding patterns in 311 patients sensitized to cat, dog and/or horse (123 m/188f, mean age 32±17 yrs) using Phadia ImmunoCAP®for rFel d 1, serum albumins (nFel d 2/nCan f 3), ...lipocalins (rFel 4/rCan f 1/rCan f 2/rEqu c 1), and rCan f 5.
Background
In vitro diagnosis using single molecules is increasingly complementing conventional extract‐based diagnosis. We explored in routine patients with animal allergy to what extent molecules ...can explain polysensitization and identify primary sensitizers and how individual IgE patterns correlate with previous pet ownership and clinical relevance.
Methods
Serum samples from 294 children and adults with suspect allergic rhino‐conjunctivitis or asthma and a positive skin prick test to cat, dog and/or horse were tested by ImmunoCAP for IgE antibodies against eleven different allergens from cat (Fel d 1,2,4,7), dog (Can f 1,2,3,4,5,6) and horse (Equ c 1).
Results
Patients monosensitized to cat (40.8%) or dog (6.1%) showed simple IgE patterns dominated by Fel d 1 (93%) and Can f 5 (67%), respectively. Double‐sensitization to cat+dog (25.9%), cat+horse (5.4%) and polysensitization (20.7%) was associated with an increasing prevalence of the cross‐reactive lipocalins Fel d 4/Can f 6/Equ c 1 and Fel d 7/Can f 1. While these lipocalins were not reliable markers for genuine sensitization per se, comparison of sIgE levels may give a clue on the primary sensitizer. Sensitizations to dog appeared to result from cross‐reactivity with cat in 48%, with half of these sensitizations lacking clinical relevance. Individual sensitization patterns strongly mirrored current or previous pet ownership with the exception of Fel d 1 which regularly caused sensitization also in non‐owners.
Conclusions
Allergen components can reasonably illuminate the molecular basis of animal (poly)sensitization in the majority of patients and are helpful in distinguishing between primary sensitization and sometimes less relevant cross‐reactivity.
Individual IgE profiles and sensitization to minor allergens strongly reflect previous pet ownership. Certain lipocalins consistently cause clinically relevant cross‐allergy between cat, dog and horse with each of them representing the potential primary sensitizer. Sensitization to dog often results from cross‐reactivity with cat. Its clinical relevance varies depending on the allergens involved. Abbreviation: SPT, skin prick test.
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