IL-24 ist ein häufiges und spezifisches IgE-Autoantigen bei Patienten mit chronisch spontaner Urtikaria

Einführung Die Ursachen der chronisch spontanen Urtikaria (CSU) sind noch nicht endgültig geklärt. Es ist beschrieben, dass bei der Entstehung der CSU Immunoglobulin E (IgE) Autoantikörper (Aak) involviert sind. Um die Ursachen der CSU besser zu verstehen, wurden Patienten mit CSU, mit idiopathischer Anaphylaxie (idA) und gesunde Kontrollen auf potenzielle IgE-Autoantigene (Aag) mittels Protein-Microarray (PMa) durchsucht und mittels ELISA gemessen. Methoden Von dem Gesamtkollektiv wurden zunächst jeweils sieben Seren von Patienten mit CSU, sieben mit idA und sieben gesunde Kontrollen mittels eines PMa mit mehr als 9000 humanen Proteinen auf IgE-Aag untersucht. Insgesamt wurden im Anschluss 1062 CSU Patientenseren und 482 Seren von gesunden Probanden auf IgE-anti-24 analysiert. Die IgE-anti-IL-24-Serumwerte wurden mithilfe eines entwickelten, IgE-anti-IL-24 spezifischen, ELISAs gemessen. Krankheitsspezifische Daten wurden mittels Fragebögen „Urtikaria Aktivitätsscore 7“ (UAS7) und „Hospital Anxiety and Depression Scale“ (HADS) erfasst, sowie mittels Messung der basophilen Zellen im Blut. Die ELISA Ergebnisse wurden mit den klinischen Daten verglichen. Ergebnisse Insgesamt wurden 226 IgE-Aag bei Patienten mit CSU gefunden, bei idA-Patienten 161 und bei gesunden Probanden 34 Aag. In mehr als 70% der Patienten konnten 31 IgE-Aag detektiert werden, acht davon waren lösliche oder membrangebundene Proteine und in der Haut exprimiert. Von diesen acht IgE-Aag hatte das IL-24, mit einem prozentualen Anteil von 1,1% (relativ zum gemessenen Gesamt-IgE) die höchste Konzentration bei allen CSU-Patienten. Eine Korrelation zwischen dem IgE-anti-IL-24-Gesamtwert und dem Gesamt-IgE im Serum konnte nicht gezeigt werden (r = 0,002, p = 0,840). Die mittels ELISA gemessenen CSU-Seren zeigten 2,2-fach höhere IgE-anti-IL-24-Werte (0,52IU/mL ± 0,24) im Vergleich zu gesunden Kontrollen (0,27 IU/mL ± 0,08, p = 0,001). 80% der CSU-Seren (874 von 1062) zeigten höhere IgE-anti-IL-24-Werte im Vergleich zu gesunden Kontrollen mit 20% (99 von 482; p<0,0001). Hohe IgE-anti-IL-24-Serumwerte korrelierten mit der CSU-Krankheitsaktivität (UAS7) und mit niedrigen Werten für basophile Zellen im Blut. CSU-Patienten mit hohen anti-HBs-Werten und mit hohen Triiodthyronin-Werten hatten niedrige IgE-anti-IL-24-Serumwerte. Hohe IgE-anti-IL-24-Serumwerte gingen mit niedrigen HADS-Ergebnissen einher. Die Populationen zeigten keine signifikanten Unterschiede bei der Alters- und Geschlechterverteilung. Schlussfolgerung CSU-Patienten haben IgE-Aak gegen diverse Aag. Das IL-24 ist ein häufiges und spezifisches IgE-Aag bei Patienten mit CSU. Hohe IgE-anti-IL-24-Serumwerte korrelieren mit hoher CSU-Krankheitsaktivität. In Zukunft könnten neue Arrays zur Messung von autoreaktivem IgE, im Speziellen von IgE-anti-IL-24, etabliert werden. Dies könnte dabei helfen, die Patienten mit CSU besser zu erkennen und effektivere Therapiemöglichkeiten zu entwickeln.Background Up to now, the causes of chronic spontaneous urticaria (CSU) haven’t been conclusively determined. Immunoglobulin E (IgE) autoantibodies (Aab) seem to play an important role in CSU’s emergence. To understand the pathogenesis of CSU in more detail, CSU-patients, patients with idiopathic anaphylaxis (idA) and healthy control subjects were screened for potential IgE-autoantigens (Aag) with protein-microarray (PMa) and measured with ELISA. Methods In total, 1,062 sera from patients with CSU and 482 sera from control subjects were collected. Seven sera of each from the CSU-patients, from idA patients and control subjects were analyzed using a PMa with more than 9,000 human proteins to screen for IgE-Aag. IgE-anti-IL-24 serum levels were measured with a developed, IgE-anti-IL-24-specific ELISA. Disease-specific data were documented in “Urticaria Activity Score 7” and “Hospital Anxiety and Depression Scale” (HADS) questionnaires, as well as measurement of basophilic cells in the blood. The ELISA results were compared with clinical data. Results In total, 226 IgE-Aag were found in CSU-patients, 161 in idA-patients and 34 in controls. In over 70% of the patients, 31 IgE-Aag were detected, eight of them were soluble or membrane bound and expressed in skin. Among these eight IgE-Aag, IL-24 had the highest concentration of all CSU-patients of 1.1% (relative to total IgE). No correlation was found between the total IgE-anti-IL-24 level and the serum total IgE level (r = 0.002, p = 0.840). CSU-patients’ serum measured with ELISA showed IgE-anti-IL-24 levels that were 2.2 times higher (0.52 IU/mL ± 0.24) compared to control subjects (0.27 IU/mL ± 0.08; p = 0.001). 80% of CSU-patients’ sera (874 of 1,062) had higher IgE-anti-IL-24 levels compared to controls with 20% (99 of 482; p<0.0001). High IgE-anti-IL-24 levels correlate with CSU disease activity (UAS7) and low levels of basophilic cells in the blood. CSU-patients with high anti-HBs levels and high Triiodthyronin levels had low IgE-anti-IL-24 levels. High IgE-anti-IL-24 levels in sera were associated with low HADS scores. The populations didn’t show any significant differences in age and gender distribution. Conclusion CSU-patients have IgE-Aab against various Aag. In our population, IL-24 was a common and specific IgE-Aag in CSU-patients. High IgE-anti-IL-24 serum levels correlate with CSU disease activity. In the future, new arrays can be established to measure autoreactive IgE, especially anti-IL-24. Our results could improve the identification of CSU-patients and may help to develop more effective and specific treatments

Proposal of 0.5 mg of protein/100 g of processed food as threshold for voluntary declaration of food allergen traces in processed food-A first step in an initiative to better inform patients and avoid fatal allergic reactions : A GA(2)LEN position paper

Background Food anaphylaxis is commonly elicited by unintentional ingestion of foods containing the allergen above the tolerance threshold level of the individual. While labeling the 14 main allergens used as ingredients in food products is mandatory in the EU, there is no legal definition of declaring potential contaminants. Precautionary allergen labeling such as "may contain traces of" is often used. However, this is unsatisfactory for consumers as they get no information if the contamination is below their personal threshold. In discussions with the food industry and technologists, it was suggested to use a voluntary declaration indicating that all declared contaminants are below a threshold of 0.5 mg protein per 100 g of food. This concentration is known to be below the threshold of most patients, and it can be technically guaranteed in most food production. However, it was also important to assess that in case of accidental ingestion of contaminants below this threshold by highly allergic patients, no fatal anaphylactic reaction could occur. Therefore, we performed a systematic review to assess whether a fatal reaction to 5mg of protein or less has been reported, assuming that a maximum portion size of 1kg of a processed food exceeds any meal and thus gives a sufficient safety margin. Methods MEDLINE and EMBASE were searched until 24 January 2021 for provocation studies and case reports in which one of the 14 major food allergens was reported to elicit fatal or life-threatening anaphylactic reactions and assessed if these occurred below the ingestion of 5mg of protein. A Delphi process was performed to obtain an expert consensus on the results. Results In the 210 studies included, in our search, no reports of fatal anaphylactic reactions reported below 5 mg protein ingested were identified. However, in provocation studies and case reports, severe reactions below 5 mg were reported for the following allergens: eggs, fish, lupin, milk, nuts, peanuts, soy, and sesame seeds. Conclusion Based on the literature studied for this review, it can be stated that cross-contamination of the 14 major food allergens below 0.5 mg/100 g is likely not to endanger most food allergic patients when a standard portion of food is consumed. We propose to use the statement "this product contains the named allergens in the list of ingredients, it may contain traces of other contaminations (to be named, e.g. nut) at concentrations less than 0.5 mg per 100 g of this product" for a voluntary declaration on processed food packages. This level of avoidance of cross-contaminations can be achieved technically for most processed foods, and the statement would be a clear and helpful message to the consumers. However, it is clearly acknowledged that a voluntary declaration is only a first step to a legally binding solution. For this, further research on threshold levels is encouraged.Peer reviewe

Proposal of 0.5 mg of protein/100 g of processed food as threshold for voluntary declaration of food allergen traces in processed food—A first step in an initiative to better inform patients and avoid fatal allergic reactions: A GA²LEN position paper

Background: Food anaphylaxis is commonly elicited by unintentional ingestion of foods containing the allergen above the tolerance threshold level of the individual. While labeling the 14 main allergens used as ingredients in food products is mandatory in the EU, there is no legal definition of declaring potential contaminants. Precautionary allergen labeling such as "may contain traces of" is often used. However, this is unsatisfactory for consumers as they get no information if the contamination is below their personal threshold. In discussions with the food industry and technologists, it was suggested to use a voluntary declaration indicating that all declared contaminants are below a threshold of 0.5 mg protein per 100 g of food. This concentration is known to be below the threshold of most patients, and it can be technically guaranteed in most food production. However, it was also important to assess that in case of accidental ingestion of contaminants below this threshold by highly allergic patients, no fatal anaphylactic reaction could occur. Therefore, we performed a systematic review to assess whether a fatal reaction to 5mg of protein or less has been reported, assuming that a maximum portion size of 1kg of a processed food exceeds any meal and thus gives a sufficient safety margin. Methods: MEDLINE and EMBASE were searched until 24 January 2021 for provocation studies and case reports in which one of the 14 major food allergens was reported to elicit fatal or life-threatening anaphylactic reactions and assessed if these occurred below the ingestion of 5mg of protein. A Delphi process was performed to obtain an expert consensus on the results. Results: In the 210 studies included, in our search, no reports of fatal anaphylactic reactions reported below 5 mg protein ingested were identified. However, in provocation studies and case reports, severe reactions below 5 mg were reported for the following allergens: eggs, fish, lupin, milk, nuts, peanuts, soy, and sesame seeds. Conclusion: Based on the literature studied for this review, it can be stated that cross-contamination of the 14 major food allergens below 0.5 mg/100 g is likely not to endanger most food allergic patients when a standard portion of food is consumed. We propose to use the statement "this product contains the named allergens in the list of ingredients, it may contain traces of other contaminations (to be named, e.g. nut) at concentrations less than 0.5 mg per 100 g of this product" for a voluntary declaration on processed food packages. This level of avoidance of cross-contaminations can be achieved technically for most processed foods, and the statement would be a clear and helpful message to the consumers. However, it is clearly acknowledged that a voluntary declaration is only a first step to a legally binding solution. For this, further research on threshold levels is encouraged

Proposal of 0.5 mg of protein/100 g of processed food as threshold for voluntary declaration of food allergen traces in processed food-A first step in an initiative to better inform patients and avoid fatal allergic reactions: A GA(2)LEN position paper

BackgroundFood anaphylaxis is commonly elicited by unintentional ingestion of foods containing the allergen above the tolerance threshold level of the individual. While labeling the 14 main allergens used as ingredients in food products is mandatory in the EU, there is no legal definition of declaring potential contaminants. Precautionary allergen labeling such as “may contain traces of” is often used. However, this is unsatisfactory for consumers as they get no information if the contamination is below their personal threshold. In discussions with the food industry and technologists, it was suggested to use a voluntary declaration indicating that all declared contaminants are below a threshold of 0.5 mg protein per 100 g of food. This concentration is known to be below the threshold of most patients, and it can be technically guaranteed in most food production. However, it was also important to assess that in case of accidental ingestion of contaminants below this threshold by highly allergic patients, no fatal anaphylactic reaction could occur. Therefore, we performed a systematic review to assess whether a fatal reaction to 5mg of protein or less has been reported, assuming that a maximum portion size of 1kg of a processed food exceeds any meal and thus gives a sufficient safety margin.MethodsMEDLINE and EMBASE were searched until 24 January 2021 for provocation studies and case reports in which one of the 14 major food allergens was reported to elicit fatal or life-threatening anaphylactic reactions and assessed if these occurred below the ingestion of 5mg of protein. A Delphi process was performed to obtain an expert consensus on the results.ResultsIn the 210 studies included, in our search, no reports of fatal anaphylactic reactions reported below 5 mg protein ingested were identified. However, in provocation studies and case reports, severe reactions below 5 mg were reported for the following allergens: eggs, fish, lupin, milk, nuts, peanuts, soy, and sesame seeds.ConclusionBased on the literature studied for this review, it can be stated that cross-contamination of the 14 major food allergens below 0.5 mg/100 g is likely not to endanger most food allergic patients when a standard portion of food is consumed. We propose to use the statement “this product contains the named allergens in the list of ingredients, it may contain traces of other contaminations (to be named, e.g. nut) at concentrations less than 0.5 mg per 100 g of this product” for a voluntary declaration on processed food packages. This level of avoidance of cross-contaminations can be achieved technically for most processed foods, and the statement would be a clear and helpful message to the consumers. However, it is clearly acknowledged that a voluntary declaration is only a first step to a legally binding solution. For this, further research on threshold levels is encouraged.</div

Proposal of 0.5 mg of protein/100 g of processed food as threshold for voluntary declaration of food allergen traces in processed food—A first step in an initiative to better inform patients and avoid fatal allergic reactions: A GA²LEN position paper

Background: Food anaphylaxis is commonly elicited by unintentional ingestion of foods containing the allergen above the tolerance threshold level of the individual. While labeling the 14 main allergens used as ingredients in food products is mandatory in the EU, there is no legal definition of declaring potential contaminants. Precautionary allergen labeling such as “may contain traces of” is often used. However, this is unsatisfactory for consumers as they get no information if the contamination is below their personal threshold. In discussions with the food industry and technologists, it was suggested to use a voluntary declaration indicating that all declared contaminants are below a threshold of 0.5 mg protein per 100 g of food. This concentration is known to be below the threshold of most patients, and it can be technically guaranteed in most food production. However, it was also important to assess that in case of accidental ingestion of contaminants below this threshold by highly allergic patients, no fatal anaphylactic reaction could occur. Therefore, we performed a systematic review to assess whether a fatal reaction to 5mg of protein or less has been reported, assuming that a maximum portion size of 1kg of a processed food exceeds any meal and thus gives a sufficient safety margin. Methods: MEDLINE and EMBASE were searched until 24 January 2021 for provocation studies and case reports in which one of the 14 major food allergens was reported to elicit fatal or life-threatening anaphylactic reactions and assessed if these occurred below the ingestion of 5mg of protein. A Delphi process was performed to obtain an expert consensus on the results. Results: In the 210 studies included, in our search, no reports of fatal anaphylactic reactions reported below 5 mg protein ingested were identified. However, in provocation studies and case reports, severe reactions below 5 mg were reported for the following allergens: eggs, fish, lupin, milk, nuts, peanuts, soy, and sesame seeds. Conclusion: Based on the literature studied for this review, it can be stated that cross-contamination of the 14 major food allergens below 0.5 mg/100 g is likely not to endanger most food allergic patients when a standard portion of food is consumed. We propose to use the statement “this product contains the named allergens in the list of ingredients, it may contain traces of other contaminations (to be named, e.g. nut) at concentrations less than 0.5 mg per 100 g of this product” for a voluntary declaration on processed food packages. This level of avoidance of cross-contaminations can be achieved technically for most processed foods, and the statement would be a clear and helpful message to the consumers. However, it is clearly acknowledged that a voluntary declaration is only a first step to a legally binding solution. For this, further research on threshold levels is encouraged

Proposal of 0.5 mg of protein/100 g of processed food as threshold for voluntary declaration of food allergen traces in processed food: A first step in an initiative to better inform patients and avoid fatal allergic reactions, A GA²LEN position paper

Background: food anaphylaxis is commonly elicited by unintentional ingestion of foods containing the allergen above the tolerance threshold level of the individual. While labeling the 14 main allergens used as ingredients in food products is mandatory in the EU, there is no legal definition of declaring potential contaminants. Precautionary allergen labeling such as "may contain traces of" is often used. However, this is unsatisfactory for consumers as they get no information if the contamination is below their personal threshold. In discussions with the food industry and technologists, it was suggested to use a voluntary declaration indicating that all declared contaminants are below a threshold of 0.5 mg protein per 100 g of food. This concentration is known to be below the threshold of most patients, and it can be technically guaranteed in most food production. However, it was also important to assess that in case of accidental ingestion of contaminants below this threshold by highly allergic patients, no fatal anaphylactic reaction could occur. Therefore, we performed a systematic review to assess whether a fatal reaction to 5mg of protein or less has been reported, assuming that a maximum portion size of 1kg of a processed food exceeds any meal and thus gives a sufficient safety margin.Methods: MEDLINE and EMBASE were searched until 24 January 2021 for provocation studies and case reports in which one of the 14 major food allergens was reported to elicit fatal or life-threatening anaphylactic reactions and assessed if these occurred below the ingestion of 5mg of protein. A Delphi process was performed to obtain an expert consensus on the results.Results: in the 210 studies included, in our search, no reports of fatal anaphylactic reactions reported below 5 mg protein ingested were identified. However, in provocation studies and case reports, severe reactions below 5 mg were reported for the following allergens: eggs, fish, lupin, milk, nuts, peanuts, soy, and sesame seeds.Conclusions: based on the literature studied for this review, it can be stated that cross-contamination of the 14 major food allergens below 0.5 mg/100 g is likely not to endanger most food allergic patients when a standard portion of food is consumed. We propose to use the statement "this product contains the named allergens in the list of ingredients, it may contain traces of other contaminations (to be named, e.g. nut) at concentrations less than 0.5 mg per 100 g of this product" for a voluntary declaration on processed food packages. This level of avoidance of cross-contaminations can be achieved technically for most processed foods, and the statement would be a clear and helpful message to the consumers. However, it is clearly acknowledged that a voluntary declaration is only a first step to a legally binding solution. For this, further research on threshold levels is encouraged.</p

Evaluation of a quality improvement intervention to reduce anastomotic leak following right colectomy (EAGLE): pragmatic, batched stepped-wedge, cluster-randomized trial in 64 countries

Background Anastomotic leak affects 8 per cent of patients after right colectomy with a 10-fold increased risk of postoperative death. The EAGLE study aimed to develop and test whether an international, standardized quality improvement intervention could reduce anastomotic leaks. Methods The internationally intended protocol, iteratively co-developed by a multistage Delphi process, comprised an online educational module introducing risk stratification, an intraoperative checklist, and harmonized surgical techniques. Clusters (hospital teams) were randomized to one of three arms with varied sequences of intervention/data collection by a derived stepped-wedge batch design (at least 18 hospital teams per batch). Patients were blinded to the study allocation. Low- and middle-income country enrolment was encouraged. The primary outcome (assessed by intention to treat) was anastomotic leak rate, and subgroup analyses by module completion (at least 80 per cent of surgeons, high engagement; less than 50 per cent, low engagement) were preplanned. Results A total 355 hospital teams registered, with 332 from 64 countries (39.2 per cent low and middle income) included in the final analysis. The online modules were completed by half of the surgeons (2143 of 4411). The primary analysis included 3039 of the 3268 patients recruited (206 patients had no anastomosis and 23 were lost to follow-up), with anastomotic leaks arising before and after the intervention in 10.1 and 9.6 per cent respectively (adjusted OR 0.87, 95 per cent c.i. 0.59 to 1.30; P = 0.498). The proportion of surgeons completing the educational modules was an influence: the leak rate decreased from 12.2 per cent (61 of 500) before intervention to 5.1 per cent (24 of 473) after intervention in high-engagement centres (adjusted OR 0.36, 0.20 to 0.64; P &lt; 0.001), but this was not observed in low-engagement hospitals (8.3 per cent (59 of 714) and 13.8 per cent (61 of 443) respectively; adjusted OR 2.09, 1.31 to 3.31). Conclusion Completion of globally available digital training by engaged teams can alter anastomotic leak rates. Registration number: NCT04270721 (http://www.clinicaltrials.gov)