PMID- 19032234
OWN - NLM
STAT- MEDLINE
DCOM- 20091130
LR  - 20081126
IS  - 1398-9995 (Electronic)
IS  - 0105-4538 (Linking)
VI  - 63
IP  - 12
DP  - 2008 Dec
TI  - Auto- and cross-reactivity to thioredoxin allergens in allergic bronchopulmonary 
      aspergillosis.
PG  - 1617-23
LID - 10.1111/j.1398-9995.2008.01777.x [doi]
AB  - BACKGROUND: Thioredoxins are cross-reactive allergens involved in the 
      pathogenesis of atopic eczema and asthma. Cross-reactivity to human thioredoxin 
      can contribute to the exacerbation of severe atopic diseases. METHODS: Human 
      thioredoxin, Asp f28 and Asp f29, two thioredoxins of Aspergillus fumigatus, and 
      thioredoxin of Malassezia sympodialis were cloned and produced as recombinant 
      proteins. Allergenicity and cross-reactivity to thioredoxins in allergic 
      bronchopulmonary aspergillosis patients were assessed by enzyme-linked 
      immunosorbent assay (ELISA), inhibition ELISA, immunoblot analysis, proliferation 
      assays and skin tests. Molecular homology modelling was used to identify 
      conserved, surface-exposed amino acids potentially involved in immunoglobulin E 
      (IgE)-binding. RESULTS: All thioredoxins, including the human enzyme, bind IgE 
      from patients with allergic bronchopulmonary aspergillosis and induce 
      allergen-specific proliferation in peripheral blood mononuclear cells and 
      positive skin reactions in thioredoxin-sensitized patients. Inhibition 
      experiments showed that the thioredoxins are cross-reactive indicating humoral 
      immune responses based on molecular mimicry. To identify structural surface 
      elements involved in cross-reactivity, the three-dimensional structures were 
      modelled based on solved thioredoxin structures. Analysis of the molecular 
      surfaces combined with sequence alignments allowed identification of conserved 
      solvent exposed amino acids distantly located in the linear sequences which 
      cluster to patches of continuous surface areas. The size of the surface areas 
      conserved between human and fungal thioredoxins correlates well with the 
      inhibitory potential of the molecules in inhibition ELISA indicating that the 
      shared amino acids are involved in IgE-binding. CONCLUSIONS: Conserved, solvent 
      exposed residues shared between different thioredoxins cluster to continuous 
      surface regions potentially forming cross-reactive conformational B-cell epitopes 
      responsible for IgE-mediated cross-reactivity and autoreactivity.
FAU - Glaser, A G
AU  - Glaser AG
AD  - Swiss Institute of Allergy and Asthma Research (SIAF), Davos, Switzerland.
FAU - Menz, G
AU  - Menz G
FAU - Kirsch, A I
AU  - Kirsch AI
FAU - Zeller, S
AU  - Zeller S
FAU - Crameri, R
AU  - Crameri R
FAU - Rhyner, C
AU  - Rhyner C
LA  - eng
PT  - Comparative Study
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - Denmark
TA  - Allergy
JT  - Allergy
JID - 7804028
RN  - 0 (Allergens)
RN  - 0 (TXN protein, human)
RN  - 37341-29-0 (Immunoglobulin E)
RN  - 52500-60-4 (Thioredoxins)
SB  - IM
MH  - Allergens/*immunology/metabolism
MH  - Amino Acid Sequence
MH  - Aspergillosis, Allergic Bronchopulmonary/*immunology/metabolism
MH  - Aspergillus fumigatus/immunology
MH  - Autoimmune Diseases/*immunology/metabolism/*microbiology
MH  - Cells, Cultured
MH  - Cross Reactions/immunology
MH  - Humans
MH  - Immunoglobulin E/biosynthesis/blood
MH  - Malassezia/immunology
MH  - Molecular Sequence Data
MH  - Skin Tests
MH  - Thioredoxins/*immunology/*metabolism
EDAT- 2008/11/27 09:00
MHDA- 2009/12/16 06:00
CRDT- 2008/11/27 09:00
PHST- 2008/11/27 09:00 [pubmed]
PHST- 2009/12/16 06:00 [medline]
PHST- 2008/11/27 09:00 [entrez]
AID - ALL1777 [pii]
AID - 10.1111/j.1398-9995.2008.01777.x [doi]
PST - ppublish
SO  - Allergy. 2008 Dec;63(12):1617-23. doi: 10.1111/j.1398-9995.2008.01777.x.