TY - THES A1 - Marschall, Talke Anu T1 - Zytotoxizität, Bioverfügbarkeit und Metabolismus kleiner Selenspezies in humanen Zellen und Entwicklung von ICP-QQQ-MS-basierten Methoden für deren Nachweis Y1 - 2017 ER - TY - GEN A1 - Henze, Andrea A1 - Raila, Jens A1 - Kempf, Caroline A1 - Reinke, Petra A1 - Sefrin, Anett A1 - Querfeld, Uwe A1 - Schweigert, Florian J. T1 - Vitamin A metabolism is changed in donors after living-kidney transplantation BT - an observational study N2 - Background The kidneys are essential for the metabolism of vitamin A (retinol) and its transport proteins retinol-binding protein 4 (RBP4) and transthyretin. Little is known about changes in serum concentration after living donor kidney transplantation (LDKT) as a consequence of unilateral nephrectomy; although an association of these parameters with the risk of cardiovascular diseases and insulin resistance has been suggested. Therefore we analyzed the concentration of retinol, RBP4, apoRBP4 and transthyretin in serum of 20 living-kidney donors and respective recipients at baseline as well as 6 weeks and 6 months after LDKT. Results As a consequence of LDKT, the kidney function of recipients was improved while the kidney function of donors was moderately reduced within 6 weeks after LDKT. With regard to vitamin A metabolism, the recipients revealed higher levels of retinol, RBP4, transthyretin and apoRBP4 before LDKT in comparison to donors. After LDKT, the levels of all four parameters decreased in serum of the recipients, while retinol, RBP4 as well as apoRBP4 serum levels of donors increased and remained increased during the follow-up period of 6 months. Conclusion LDKT is generally regarded as beneficial for allograft recipients and not particularly detrimental for the donors. However, it could be demonstrated in this study that a moderate reduction of kidney function by unilateral nephrectomy, resulted in an imbalance of components of vitamin A metabolism with a significant increase of retinol and RBP4 and apoRBP4 concentration in serum of donors. T3 - Zweitveröffentlichungen der Universität Potsdam : Mathematisch-Naturwissenschaftliche Reihe - 373 KW - Donors KW - glomerular filtration rate KW - kidney transplantation KW - retinol KW - retinol-binding protein 4 KW - transthyretin Y1 - 2017 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:kobv:517-opus4-400942 ER - TY - JOUR A1 - Raila, Jens A1 - Kawashima, Chiho A1 - Sauerwein, Helga A1 - Hülsmann, Nadine A1 - Knorr, Christoph A1 - Myamoto, Akio A1 - Schweigert, Florian J. T1 - Validation of blood vitamin A concentrations in cattle: comparison of a new cow-side test (iCheck™ FLUORO) with high-performance liquid chromatography (HPLC) JF - BMC veterinary research N2 - Background: Plasma concentration of retinol is an accepted indicator to assess the vitamin A (retinol) status in cattle. However, the determination of vitamin A requires a time consuming multi-step procedure, which needs specific equipment to perform extraction, centrifugation or saponification prior to high-performance liquid chromatography (HPLC). Methods: The concentrations of retinol in whole blood (n = 10), plasma (n = 132) and serum (n = 61) were measured by a new rapid cow-side test (iCheck™ FLUORO) and compared with those by HPLC in two independent laboratories in Germany (DE) and Japan (JP). Results: Retinol concentrations in plasma ranged from 0.033 to 0.532 mg/L, and in serum from 0.043 to 0.360 mg/L (HPLC method). No significant differences in retinol levels were observed between the new rapid cow-side test and HPLC performed in different laboratories (HPLC vs. iCheck™ FLUORO: 0.320 ± 0.047 mg/L vs. 0.333 ± 0.044 mg/L, and 0.240 ± 0.096 mg/L vs. 0.241 ± 0.069 mg/L, lab DE and lab JP, respectively). A similar comparability was observed when whole blood was used (HPLC vs. iCheck™ FLUORO: 0.353 ± 0.084 mg/L vs. 0.341 ± 0.064 mg/L). Results showed a good agreement between both methods based on correlation coefficients of r2 = 0.87 (P < 0.001) and Bland-Altman blots revealed no significant bias for all comparison. Conclusions: With the new rapid cow-side test (iCheck™ FLUORO) retinol concentrations in cattle can be reliably assessed within a few minutes and directly in the barn using even whole blood without the necessity of prior centrifugation. The ease of the application of the new rapid cow-side test and its portability can improve the diagnostic of vitamin A status and will help to control vitamin A supplementation in specific vitamin A feeding regimes such as used to optimize health status in calves or meat marbling in Japanese Black cattle. KW - Cattle KW - Vitamin A KW - Biomarker KW - Blood KW - Method comparison KW - Cow-side assay Y1 - 2017 U6 - https://doi.org/10.1186/s12917-017-1042-3 VL - 13 PB - BioMed Central CY - London ER - TY - GEN A1 - Raila, Jens A1 - Kawashima, Chiho A1 - Sauerwein, Helga A1 - Hülsmann, Nadine A1 - Knorr, Christoph A1 - Myamoto, Akio A1 - Schweigert, Florian J. T1 - Validation of blood vitamin A concentrations in cattle: comparison of a new cow-side test (iCheck™ FLUORO) with high-performance liquid chromatography (HPLC) N2 - Background: Plasma concentration of retinol is an accepted indicator to assess the vitamin A (retinol) status in cattle. However, the determination of vitamin A requires a time consuming multi-step procedure, which needs specific equipment to perform extraction, centrifugation or saponification prior to high-performance liquid chromatography (HPLC). Methods: The concentrations of retinol in whole blood (n = 10), plasma (n = 132) and serum (n = 61) were measured by a new rapid cow-side test (iCheck™ FLUORO) and compared with those by HPLC in two independent laboratories in Germany (DE) and Japan (JP). Results: Retinol concentrations in plasma ranged from 0.033 to 0.532 mg/L, and in serum from 0.043 to 0.360 mg/L (HPLC method). No significant differences in retinol levels were observed between the new rapid cow-side test and HPLC performed in different laboratories (HPLC vs. iCheck™ FLUORO: 0.320 ± 0.047 mg/L vs. 0.333 ± 0.044 mg/L, and 0.240 ± 0.096 mg/L vs. 0.241 ± 0.069 mg/L, lab DE and lab JP, respectively). A similar comparability was observed when whole blood was used (HPLC vs. iCheck™ FLUORO: 0.353 ± 0.084 mg/L vs. 0.341 ± 0.064 mg/L). Results showed a good agreement between both methods based on correlation coefficients of r2 = 0.87 (P < 0.001) and Bland-Altman blots revealed no significant bias for all comparison. Conclusions: With the new rapid cow-side test (iCheck™ FLUORO) retinol concentrations in cattle can be reliably assessed within a few minutes and directly in the barn using even whole blood without the necessity of prior centrifugation. The ease of the application of the new rapid cow-side test and its portability can improve the diagnostic of vitamin A status and will help to control vitamin A supplementation in specific vitamin A feeding regimes such as used to optimize health status in calves or meat marbling in Japanese Black cattle. T3 - Zweitveröffentlichungen der Universität Potsdam : Mathematisch-Naturwissenschaftliche Reihe - 381 KW - Biomarker KW - Blood KW - Cattle KW - Cow-side assay KW - Method comparison KW - Vitamin A Y1 - 2017 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:kobv:517-opus4-401978 ER - TY - THES A1 - Stadion, Mandy T1 - Validation and Characterization of lfi202b and Zfp69, two Novel Disease Genes in Obesity-Associated Insulin Resistance Y1 - 2017 ER - TY - JOUR A1 - Wallmeyer, Leonie A1 - Dietert, Kristina A1 - Sochorova, Michaela A1 - Gruber, Achim D. A1 - Kleuser, Burkhard A1 - Vavrova, Katerina A1 - Hedtrich, Sarah T1 - TSLP is a direct trigger for T cell migration in filaggrin-deficient skin equivalents JF - Scientific reports N2 - Mutations in the gene encoding for filaggrin (FLG) are major predisposing factors for atopic dermatitis (AD). Besides genetic predisposition, immunological dysregulations considerably contribute to its pathophysiology. For example, thymic stromal lymphopoietin (TSLP) is highly expressed in lesional atopic skin and significantly contributes to the pathogenesis of AD by activating dendritic cells that then initiate downstream effects on, for example, T cells. However, little is known about the direct interplay between TSLP, filaggrin-deficient skin and other immune cells such as T lymphocytes. In the present study, FLG knockdown skin equivalents, characterised by intrinsically high TSLP levels, were exposed to activated CD4(+) T cells. T cell exposure resulted in an inflammatory phenotype of the skin equivalents. Furthermore, a distinct shift from a Th1/Th17 to a Th2/Th22 profile was observed following exposure of T cells to filaggrin-deficient skin equivalents. Interestingly, TSLP directly stimulated T cell migration exclusively in filaggrin-deficient skin equivalents even in the absence of dendritic cells, indicating a hitherto unknown role of TSLP in the pathogenesis of AD. Y1 - 2017 U6 - https://doi.org/10.1038/s41598-017-00670-2 SN - 2045-2322 VL - 7 PB - Nature Publ. Group CY - London ER - TY - JOUR A1 - Marschall, Talke Anu A1 - Kroepfl, Nina A1 - Jensen, Kenneth Bendix A1 - Bornhorst, Julia A1 - Meermann, B. A1 - Kühnelt, Doris A1 - Schwerdtle, Tanja T1 - Tracing cytotoxic effects of small organic Se species in human liver cells back to total cellular Se and Se metabolites JF - Metallomics N2 - Small selenium (Se) species play a major role in the metabolism, excretion and dietary supply of the essential trace element selenium. Human cells provide a valuable tool for investigating currently unresolved issues on the cellular mechanisms of Se toxicity and metabolism. In this study, we developed two isotope dilution inductively coupled plasma tandem-mass spectrometry based methods and applied them to human hepatoma cells (HepG2) in order to quantitatively elucidate total cellular Se concentrations and cellular Se species transformations in relation to the cytotoxic effects of four small organic Se species. Species-and incubation time-dependent results were obtained: the two major urinary excretion metabolites trimethylselenonium (TMSe) and methyl-2-acetamido-2-deoxy-1-seleno-beta- D-galactopyranoside (SeSugar 1) were taken up by the HepG2 cells in an unmodified manner and did not considerably contribute to the Se pool. In contrast, Se-methylselenocysteine (MeSeCys) and selenomethionine (SeMet) were taken up in higher amounts, they were largely incorporated by the cells (most likely into proteins) and metabolized to other small Se species. Two new metabolites of MeSeCys, namely gamma-glutamyl-Se-methylselenocysteine and Se-methylselenoglutathione, were identified by means of HPLC-electrospray-ionization-Orbitrap-MS. They are certainly involved in the (de-) toxification modes of Se metabolism and require further investigation. Y1 - 2017 U6 - https://doi.org/10.1039/c6mt00300a SN - 1756-5901 SN - 1756-591X VL - 9 SP - 268 EP - 277 PB - Royal Society of Chemistry CY - Cambridge ER - TY - JOUR A1 - Witt, Barbara A1 - Meyer, Sören A1 - Ebert, Franziska A1 - Francesconi, Kevin A. A1 - Schwerdtle, Tanja T1 - Toxicity of two classes of arsenolipids and their water-soluble metabolites in human differentiated neurons JF - Archives of toxicology : official journal of EUROTOX N2 - Arsenolipids are lipid-soluble organoarsenic compounds, mainly occurring in marine organisms, with arsenic-containing hydrocarbons (AsHCs) and arsenic-containing fatty acids (AsFAs) representing two major subgroups. Recently, toxicity studies of several arsenolipids showed a high cytotoxic potential of those arsenolipids in human liver and bladder cells. Furthermore, feeding studies with Drosophila melanogaster indicated an accumulation of arsenolipids in the fruit fly’s brain. In this study, the neurotoxic potential of three AsHCs, two AsFAs and three metabolites (dimethylarsinic acid, thio/oxo-dimethylarsenopropanoic acid) was investigated in comparison to the toxic reference arsenite (iAsIII) in fully differentiated human brain cells (LUHMES cells). Thereby, in the case of AsHCs both the cell number and cell viability were reduced in a low micromolar concentration range comparable to iAsIII, while AsFAs and the applied metabolites were less toxic. Mechanistic studies revealed that AsHCs reduced the mitochondrial membrane potential, whereas neither iAsIII nor AsFAs had an impact. Furthermore, neurotoxic mechanisms were investigated by examining the neuronal network. Here, AsHCs massively disturbed the neuronal network and induced apoptotic effects, while iAsIII and AsFAs showed comparatively lesser effects. Taking into account the substantial in vitro neurotoxic potential of the AsHCs and the fact that they could transfer across the physiological barriers of the brain, a neurotoxic potential in vivo for the AsHCs cannot be excluded and needs to be urgently characterized. KW - Arsenolipids KW - Neurons KW - Cytotoxicity KW - Neurotoxicity KW - Arsenic-containing hydrocarbons KW - Arsenic-containing fatty acids Y1 - 2017 U6 - https://doi.org/10.1007/s00204-017-1933-x SN - 0340-5761 SN - 1432-0738 VL - 91 SP - 3121 EP - 3134 PB - Springer CY - Heidelberg ER - TY - JOUR A1 - Strehlau, Jenny A1 - Weber, Till A1 - Luerenbaum, Constantin A1 - Bornhorst, Julia A1 - Galla, Hans-Joachim A1 - Schwerdtle, Tanja A1 - Winter, Martin A1 - Nowak, Sascha T1 - Towards quantification of toxicity of lithium ion battery electrolytes - development and validation of a liquid-liquid extraction GC-MS method for the determination of organic carbonates in cell culture materials JF - Analytical and bioanalytical chemistry : a merger of Fresenius' journal of analytical chemistry, Analusis and Quimica analitica N2 - A novel method based on liquid-liquid extraction with subsequent gas chromatography separation and mass spectrometric detection (GC-MS) for the quantification of organic carbonates in cell culture materials is presented. Method parameters including the choice of extraction solvent, of extraction method and of extraction time were optimised and the method was validated. The setup allowed for determination within a linear range of more than two orders of magnitude. The limits of detection (LODs) were between 0.0002 and 0.002 mmol/L and the repeatability precisions were in the range of 1.5-12.9%. It could be shown that no matrix effects were present and recovery rates between 98 and 104% were achieved. The methodology was applied to cell culture models incubated with commercial lithium ion battery (LIB) electrolytes to gain more insight into the potential toxic effects of these compounds. The stability of the organic carbonates in cell culture medium after incubation was studied. In a porcine model of the blood-cerebrospinal fluid (CSF) barrier, it could be shown that a transfer of organic carbonates into the brain facing compartment took place. KW - Liquid-liquid extraction KW - GC-MS KW - Lithiumion battery (LIB) KW - Organic carbonates KW - Cell culture materials Y1 - 2017 U6 - https://doi.org/10.1007/s00216-017-0549-6 SN - 1618-2642 SN - 1618-2650 VL - 409 SP - 6123 EP - 6131 PB - Springer CY - Heidelberg ER - TY - THES A1 - Trendelenburg, Valérie T1 - Therapie der Erdnussallergie durch orale Immuntherapie T1 - Oral immunotherapy for the treatment of peanut allergy BT - eine randomisierte Placebo-kontrollierte Studie N2 - Einleitung: Die Erdnussallergie zählt zu den häufigsten Nahrungsmittelallergien im Kindesalter. Bereits kleine Mengen Erdnuss (EN) können zu schweren allergischen Reaktionen führen. EN ist der häufigste Auslöser einer lebensbedrohlichen Anaphylaxie bei Kindern und Jugendlichen. Im Gegensatz zu anderen frühkindlichen Nahrungsmittelallergien entwickeln Patienten mit einer EN-Allergie nur selten eine natürliche Toleranz. Seit mehreren Jahren wird daher an kausalen Therapiemöglichkeiten für EN-Allergiker, insbesondere an der oralen Immuntherapie (OIT), geforscht. Erste kleinere Studien zur OIT bei EN-Allergie zeigten erfolgsversprechende Ergebnisse. Im Rahmen einer randomisierten, doppelblind, Placebo-kontrollierten Studie mit größerer Fallzahl werden in der vorliegenden Arbeit die klinische Wirksamkeit und Sicherheit dieser Therapieoption bei Kindern mit EN-Allergie genauer evaluiert. Des Weiteren werden immunologische Veränderungen sowie die Lebensqualität und Therapiebelastung unter OIT untersucht. Methoden: Kinder zwischen 3-18 Jahren mit einer IgE-vermittelten EN-Allergie wurden in die Studie eingeschlossen. Vor Beginn der OIT wurde eine orale Provokation mit EN durchgeführt. Die Patienten wurden 1:1 randomisiert und entsprechend der Verum- oder Placebogruppe zugeordnet. Begonnen wurde mit 2-120 mg EN bzw. Placebo pro Tag, abhängig von der Reaktionsdosis bei der oralen Provokation. Zunächst wurde die tägliche OIT-Dosis alle zwei Wochen über etwa 14 Monate langsam bis zu einer Erhaltungsdosis von mindestens 500 mg EN (= 125 mg EN-Protein, ~ 1 kleine EN) bzw. Placebo gesteigert. Die maximal erreichte Dosis wurde dann über zwei Monate täglich zu Hause verabreicht. Im Anschluss erfolgte erneut eine orale Provokation mit EN. Der primäre Endpunkt der Studie war die Anzahl an Patienten der Verum- und Placebogruppe, die unter oraler Provokation nach OIT ≥1200 mg EN vertrugen (=„partielle Desensibilisierung“). Sowohl vor als auch nach OIT wurde ein Hautpricktest mit EN durchgeführt und EN-spezifisches IgE und IgG4 im Serum bestimmt. Außerdem wurden die Basophilenaktivierung sowie die Ausschüttung von T-Zell-spezifischen Zytokinen nach Stimulation mit EN in vitro gemessen. Anhand von Fragebögen wurde die Lebensqualität vor und nach OIT sowie die Therapiebelastung während OIT erfasst. Ergebnisse: 62 Patienten wurden in die Studie eingeschlossen und randomisiert. Nach etwa 16 Monaten unter OIT zeigten 74,2% (23/31) der Patienten der Verumgruppe und nur 16,1% (5/31) der Placebogruppe eine „partielle Desensibilisierung“ gegenüber EN (p<0,001). Im Median vertrugen Patienten der Verumgruppe 4000 mg EN (~8 kleine EN) unter der Provokation nach OIT wohingegen Patienten der Placebogruppe nur 80 mg EN (~1/6 kleine EN) vertrugen (p<0,001). Fast die Hälfte der Patienten der Verumgruppe (41,9%) tolerierten die Höchstdosis von 18 g EN unter Provokation („komplette Desensibilisierung“). Es zeigte sich ein vergleichbares Sicherheitsprofil unter Verum- und Placebo-OIT in Bezug auf objektive Nebenwirkungen. Unter Verum-OIT kam es jedoch signifikant häufiger zu subjektiven Nebenwirkungen wie oralem Juckreiz oder Bauchschmerzen im Vergleich zu Placebo (3,7% der Verum-OIT-Gaben vs. 0,5% der Placebo-OIT-Gaben, p<0,001). Drei Kinder der Verumgruppe (9,7%) und sieben Kinder der Placebogruppe (22,6%) beendeten die Studie vorzeitig, je zwei Patienten beider Gruppen aufgrund von Nebenwirkungen. Im Gegensatz zu Placebo, zeigten sich unter Verum-OIT signifikante immunologische Veränderungen. So kam es zu einer Abnahme des EN-spezifischen Quaddeldurchmessers im Hautpricktest, einem Anstieg der EN-spezifischen IgG4-Werte im Serum sowie zu einer verminderten EN-spezifischen Zytokinsekretion, insbesondere der Th2-spezifischen Zytokine IL-4 und IL-5. Hinsichtlich der EN-spezifischen IgE-Werte sowie der EN-spezifischen Basophilenaktivierung zeigten sich hingegen keine Veränderungen unter OIT. Die Lebensqualität von Kindern der Verumgruppe war nach OIT signifikant verbessert, jedoch nicht bei Kindern der Placebogruppe. Während der OIT wurde die Therapie von fast allen Kindern (82%) und Müttern (82%) als positiv bewertet (= niedrige Therapiebelastung). Diskussion: Die EN-OIT führte bei einem Großteil der EN-allergischen Kinder zu einer Desensibilisierung und einer deutlich erhöhten Reaktionsschwelle auf EN. Somit sind die Kinder im Alltag vor akzidentellen Reaktionen auf EN geschützt, was die Lebensqualität der Kinder deutlich verbessert. Unter den kontrollierten Studienbedingungen zeigte sich ein akzeptables Sicherheitsprofil, mit vorrangig milder Symptomatik. Die klinische Desensibilisierung ging mit Veränderungen auf immunologischer Ebene einher. Langzeitstudien zur EN-OIT müssen jedoch abgewartet werden, um die klinische und immunologische Wirksamkeit hinsichtlich einer möglichen langfristigen oralen Toleranzinduktion sowie die Sicherheit unter langfristiger OIT zu untersuchen, bevor das Therapiekonzept in die Praxis übertragen werden kann. N2 - Background: Peanut (PN) allergy is one of the most common food allergies in childhood. Even very small amounts of PN can elicit severe allergic reactions in patients. PN is the most common cause of life-threatening anaphylaxis in children and adolescents. A natural oral tolerance development in patients with PN allergy is rare when compared to other food allergies in early childhood. Over the last years, a lot of research has been conducted on causal treatment options for food allergy, especially on oral immunotherapy (OIT). First small trials on OIT for PN with small sample size showed promising results. This randomized, double blind, placebo-controlled study with a larger sample size aims to investigate the clinical efficacy and safety of this treatment option in children with PN allergy. In addition, effects of OIT on immunological parameters and the quality of life as well as the burden of treatment will be examined. Methods: Children aged 3-18 years with IgE-mediated PN allergy were included in the study. Before starting OIT an oral food challenge with PN was performed. Patients were randomly assigned (1:1) to receive verum- or placebo-OIT. Depending on the eliciting dose during the oral food challenge, OIT started with 2-120 mg PN or placebo on a daily basis. OIT-doses were gradually increased every two weeks up to a maintenance dose of at least 500 mg PN (= 125 mg PN protein, ~1 small PN) or placebo over a period of approximately 14 months. After reaching the highest dose, patients ingested the dose daily for two months at home followed by a repeated oral food challenge with PN. The primary endpoint of the study was the proportion of patients in the verum- and placebo group tolerating ≥1200 mg PN at final food challenge after OIT (=„partial desensitization“). Before and after OIT a skin prick test (SPT) with PN was conducted and PN -specific IgE and IgG4-levels were measured in serum. In addition, mechanistic studies on basophil reactivity and cytokine production of T-cells were performed after stimulation with PN in vitro. Disease-specific questionnaires were used to measure quality of life before and after OIT and burden of treatment during OIT. Results: 62 patients were included in the study and randomized. After a median of 16 months on OIT 74.2% (23/32) of PN OIT subjects and only 16.1% (5/31) of placebo subjects showed a partial desensitization to PN (p<0,001). During oral food challenge after OIT, PN OIT patients tolerated a median dose of 4000 mg PN (~8 small PN) whereas placebo subjects tolerated only 80 mg PN (~1/6 small PN) (p<0.001). Almost half of the PN OIT subjects (41.9%) tolerated the highest dose of 18 g PN during final food challenge (=„complete desensitization”). There was a comparable safety profile during verum and placebo OIT regarding objective adverse events. However, subjective symptoms as oral pruritus or abdominal pain occurred significantly more often during verum OIT compared to placebo (3.7% of verum OIT-doses vs. 0.52% of placebo OIT-doses, p<0.001). Three PN OIT subjects (9.7%) and seven placebo subjects (22.6%) discontinued the study, two subjects of each group due to allergic side effects. In contrast to placebo, significant immunological changes could be shown during verum OIT with a reduction in PN-specific SPT wheal size, an increase in PN -specific IgG4-serum levels and a decrease in PN-specific cytokine production, especially of Th2-specific cytokines IL-4 and IL-5. With regard to PN-specific IgE levels and PN-specific basophil reactivity, no changes were observed during OIT. Quality of life in PN OIT children significantly improved after treatment but not in placebo. During OIT almost all children (82%) and mothers (82%) were positive about this treatment option (= low burden of treatment). Discussion: PN-OIT successfully induced desensitization in most of the PN-allergic children with a marked increase in the threshold to PN. Consequently, children will be protected from accidental reaction to PN in everyday life, leading to a significant improvement of their quality of life. OIT showed an acceptable safety profile under strict conditions of this clinical trial, with mainly mild symptoms. Clinical desensitization came along with immunological changes. However, long-term studies on PN-OIT are warranted, in order to investigate the clinical and immunological efficacy regarding a possible long-term oral tolerance induction as well as long-term safety, before this treatment option may be implemented as part of routine practice. KW - Erdnussallergie KW - Nahrungsmittelallergie KW - orale Immuntherapie KW - Desensibilisierung KW - Anaphylaxie KW - peanut allergy KW - food allergy KW - oral immunotherapy KW - desensitization KW - anaphylaxis Y1 - 2017 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:kobv:517-opus4-403557 ER -