[show abstract][hide abstract] ABSTRACT: Background: A 29-year-old female presented with a first-time anaphylactic reaction.
History revealed the intake of “Schwarzbeernocken”, a Tyrolean speciality containing
blueberries, 1 hour prior to the onset of symptoms. We aimed to identify the culprit
allergen. Methods: Serum from a blueberry allergic donor was studied for IgE reactivity
to blueberry, mugwort (Artemisia vulgaris) and birch (Betula verrucosa) pollen extract
in IgE immunoblot experiments. IgE inhibition experiments and N-terminal sequencing
were performed to further identify the putative blueberry allergen. In addition, blueberry
extract was evaluated for cross-reactive allergens with sera from a Bet v 1- and a monosensitized
mugwort pollen-allergic patient.
Results: Blueberries contain a 9 kDa allergen which cross-reacts with Pru p 3, the nonspecific lipid transfer protein from peach, and shows sequence homology with cabbage lipid transfer protein. No allergen homologous to Bet v 1 could be identified in blueberries.
Conclusion: Blueberry lipid transfer protein represents a relevant food allergen which can cause severe anaphylactic reactions. However, blueberries apparently do not contain any Bet v 1-homologue. This protein family is found in many other foods and known as the most common cause of oral allergy syndrome in the Northern hemisphere.
[show abstract][hide abstract] ABSTRACT: Allergen-specific subcutaneous immunotherapy (SCIT) is an antigen-specific therapy of IgE-mediated allergies. In the present study, we analyze the epitope specificities of antibody responses induced by SCIT with allergen extracts from pollen of trees belonging to the order Fagales (birch, alder, hazel) adsorbed onto aluminum hydroxide.
The IgE, IgG1-4 and IgA responses to defined recombinant allergens (birch pollen: Bet v 1; alder pollen: Aln g 1; hazel pollen: Cor a 1; apple: Mal d 1) as well as to Bet v 1-derived recombinant fragments and synthetic peptides were analyzed in sera from patients who had undergone SCIT for different periods of time.
Long-term SCIT (>1 year; cumulative dose >1,000,000 SQ units) induced more pronounced IgG1, IgG2 and IgG4 responses to Bet v 1 and Bet v 1-related allergens according to the degree of sequence homology (Bet v 1>Aln g 1>Cor a 1>Mal d 1) than short-term SCIT (<1 year; cumulative dose <1,000,000 SQ units). In contrast to patients treated for <1 year, patients treated for >1 year mounted distinct IgG1, IgG2 and IgG4 responses against sequential Bet v 1 epitopes. No relevant allergen-specific IgA or IgG3 responses were induced by short- or long-term SCIT. Using a competitive ELISA assay, it could be shown that serum IgG from patients undergoing long-term SCIT inhibited IgE reactivity to Bet v 1 better than IgG from patients undergoing short-term SCIT.
SCIT with allergen extracts adsorbed onto aluminum hydroxide induces IgG responses against new epitopes that block IgE binding and cross-react with structurally related allergens depending, among other factors, on duration of treatment and cumulative injected dose.
International Archives of Allergy and Immunology 09/2009; 151(1):17-27. · 2.25 Impact Factor
[show abstract][hide abstract] ABSTRACT: Beech and oak pollen are potential allergen sources with a world-wide distribution.
We aimed to characterize the allergen profile of beech and oak pollen and to study cross-reactivities with birch and grass pollen allergens.
Sera from tree pollen-allergic patients with evidence for beech and oak pollen sensitization from Basel, Switzerland, (n=23) and sera from birch pollen-allergic patients from Vienna, Austria, (n=26) were compared in immunoblot experiments for IgE reactivity to birch (Betula pendula syn. verrucosa), beech (Fagus sylvatica) and oak (Quercus alba) pollen allergens. Subsequently, beech and oak pollen allergens were characterized by IgE inhibition experiments with purified recombinant and natural allergens and with allergen-specific antibody probes. Birch-, beech- and oak pollen-specific IgE levels were determined by ELISA.
Beech and oak pollen contain allergens that cross-react with the birch pollen allergens Bet v 1, Bet v 2 and Bet v 4 and with the berberine bridge enzyme-like allergen Phl p 4 from timothy grass pollen. Sera from Swiss and Austrian patients exhibited similar IgE reactivity profiles to birch, beech and oak pollen extracts. IgE levels to beech and oak pollen allergens were lower than those to birch pollen allergens.
IgE reactivity to beech pollen is mainly due to cross-reactivity with birch pollen allergens, and a Phl p 4-like molecule represented another predominant IgE-reactive structure in oak pollen. The characterization of beech and oak pollen allergens and their cross-reactivity is important for the diagnosis and treatment of beech and oak pollen allergy.
[show abstract][hide abstract] ABSTRACT: We have recently described a system for the generation of dendritic cells (DC) and Langerhans cells (LC) from defined CD34+ precursors purified from peripheral blood of healthy adult volunteers. This study has now been extended by the characterization of two distinct subpopulations of CD34+ cells in normal human peripheral blood as defined by the expression of the skin homing receptor cutaneous lymphocyte-associated antigen (CLA). CD34+/CLA+ cells from normal peripheral blood were found to be CD71LOW/CD11a+/CD11b+/CD49d+/CD45RA+ whereas CD34+/CLA- cells displayed the CD71+/CD11aLOW/CD11bLOW/CD49d(+)/ CD45RA(LOW) phenotype. To determine the differentiation pathways of these two cell populations, CD34+ cells were sorted into CLA+ and CLA- fractions, stimulated with GM-CSF and TNF-alpha in vitro, and then were cultured for 10 to 18 d. Similar to unfractionated CD34+ cells, the progeny of both cell populations contained sizable numbers (12-22%) of dendritically shaped, CD1a+/HLA-DR cells. In addition to differences in their motility, the two dendritic cell populations generated differed from each other by the expression of LC-specific structures. Only the precursors expressing the skin homing receptor were found to differentiate into LC as evidenced by the presence of Birbeck granules. In contrast, CLA precursor cells generated a CD1a+ DC population devoid of Birbeck granule-containing LC. Provided that comparable mechanisms as found in this study are also operative in vivo, we postulate that the topographic organization of the DC system is already determined, at least in part, at the progenitor level.
Journal of Experimental Medicine 04/1997; 185(6):1131-6. · 13.21 Impact Factor
[show abstract][hide abstract] ABSTRACT: Human Langerhans cells (LC) are CD1a+ dendritic cells (DC) that function as potent antigen-presenting cells for primary and secondary immune responses. Limitations in DC/LC numbers, imposed by difficult and tedious isolation procedures, have so far precluded their use as immunogens in the generation and/or augmentation of host responses against various pathogens. Therefore, we have developed a procedure for the generation of human DC/LC from CD34+ hematopoietic progenitor cells (HPC) isolated (mean: 0.7 x 10(6)/ buffy coat and 2.6 x 10(6)/leukapheresis product) and purified ( > 95%) from the peripheral blood of healthy adults. In vitro stimulation of these cells with granulocyte-macrophage colony-stimulating factor (GM-CSF) and tumor necrosis factor (TNF)-alpha led to their vigorous proliferation and differentiation resulting in the emergence of CD45+/CD68+/CD3-/CD19-/CD56- leukocytes some of which (mean: 12%) express CD1a and exhibit anti-CD4 and anti-major histocompatibility complex (MHC) class II reactivity. These CD1a- leukocytes include (1) LC as evidenced by the presence of Birbeck granules (BG), (2) CD14+ monocytes, and (3) Birbeck granule-negative cells with a dendritic morphology. Addition of interleukin (IL)-4 to the cytokine cocktail interfered with the development of monocytes and led to a reduction in the overall yield but, on the other hand, resulted in an increased percentage of CD1a+ cells (mean: 24%) among all cells generated. In vitro generated CD1a+, but not CD1a- HPC-derived cells are potent stimulators of the primary mixed leukocyte reaction and, as such, promising candidates for vaccination purposes.