Carrot allergy: Double-blinded, placebo-controlled food challenge and identification of allergens

Ballmer‐Weber, Barbara; Wüthrich, B; Wangorsch, Andrea; Fötisch, Kay; Altmann, Friedrich; Vieths, Stefan

doi:10.1067/mai.2001.116430

Cited by 145 publications

(143 citation statements)

References 31 publications

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“…Here, we applied the same approach to study Dau c 1‐specific T cells and provide strong evidence that the major carrot allergen may induce T‐cell responses independently from Bet v 1. These findings complement previous findings on Bet v 1‐independent IgE responses to Dau c 1 in carrot‐allergic individuals 9, 12, 13.…”

Section: Discussionsupporting

confidence: 91%

“…The nonsensitizing proteins Api g 1 and Mal d 1 lack major T‐cell epitopes, whereas the major sensitizer Bet v 1 contains the region Bet v 1 142–156 recognized by 63% of birch pollen‐allergic patients. Dau c 1 confirms these findings as it contains an immunodominant T‐cell‐activating region and induces IgE responses independently from Bet v 1 9, 12, 13. Beyond that, a high proportion of Dau c 1 remained intact for 48 h of incubation with endolysosomal proteases (Fig.…”

Section: Discussionsupporting

confidence: 72%

“…Thus, in addition to cross‐reactivity with the major birch pollen allergen, Dau c 1 itself may show sensitizing activity. This evidence is supported by the demonstration of Bet v 1‐independent IgE responses to Dau c 1 in patients 1, 9, 12, 13 and by immunological properties of Dau c 1 that are characteristic for sensitizing allergens, namely high stability to endolysosomal proteolysis and the existence of major T‐cell‐activating regions. We conclude that Dau c 1 has a special status among Bet v 1‐related food allergens.…”

Section: Discussionmentioning

confidence: 74%

“…All patients reported allergic symptoms after ingestion of raw carrot. In addition, patients 1, 5, 10, 13, and 20 had been positive in double‐blind placebo‐controlled food challenges with carrot 9. All patients displayed Dau c 1‐specific IgE as determined by ELISA (data not shown).…”

Section: Methodsmentioning

confidence: 96%

“…However, comparisons of the surface topology and physicochemical properties of Dau c 1 and Bet v 1 have revealed that the two proteins share only some but not all IgE epitopes 8. Indeed, IgE binding to Dau c 1 could not be inhibited by Bet v 1 in a subset of birch pollen‐allergic patients with carrot allergy 9. This observation clearly differed from other Bet v 1‐related food allergens, in particular from Api g 1 in celery, which has an aa sequence similarity of 93% (81% identity) with Dau c 1 7.…”

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confidence: 99%

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Characterization of the T-cell response to Dau c 1, the Bet v 1-homolog in carrot

Zulehner

Nagl

Briza

et al. 2016

Allergy

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BackgroundIn contrast to other Bet v 1‐related food allergens, the major carrot allergen, Dau c 1, has been suggested to induce food allergy independently from Bet v 1. As T cells are crucial in the sensitization process, we sought to characterize the T‐cell response to Dau c 1 and its cross‐reactivity with Bet v 1.MethodsDau c 1‐specific T‐cell lines (TCL) and clones (TCC) established from PBMC of birch pollen‐allergic patients with carrot allergy were analyzed for reactivity to Bet v 1, epitope specificity, allergen‐induced cytokine secretion, and expression of integrins α4β7 and α4β1, critical for gut and lung homing, respectively. mRNA expression of GATA3 and Tbet was analyzed in sorted CD3+ CD4+ CFSE low cells proliferating upon stimulation of PBMC with Dau c 1 or Bet v 1. Dau c 1 was incubated with endolysosomal proteases, and the resulting fragments were identified by mass spectrometry.ResultsAmong 14 distinct T‐cell‐activating regions, Dau c 1139–153 was recognized by 55% of the patients. Only 6 of 15 (40%) Dau c 1‐specific TCL and 9 of 21 (43%) TCC reacted with Bet v 1. Bet v 1‐nonreactive TCC were mainly Th1‐like and showed a higher expression of the integrin β7 and a significantly lower expression of the integrin β1 than Bet v 1‐positive TCC. A Th1‐like response was also detected in Dau c 1‐reactive CD3+ CD4+ CFSE low cells. Full‐length Dau c 1 was still detectable after 48 h of endolysosomal degradation. Proteolytic fragments of Dau c 1 matched its T‐cell‐activating regions.ConclusionDau c 1 displays several characteristics of sensitizing allergens, namely a major T‐cell‐activating region, low susceptibility to endolysosomal degradation, and induction of a Bet v 1‐independent T‐cell response. These cellular insights confirm that the major carrot allergen has a special status among Bet v 1‐related food allergens.

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Section: Discussionsupporting

confidence: 91%