PMID- 15969685
OWN - NLM
STAT- MEDLINE
DCOM- 20051208
LR  - 20061115
IS  - 0105-4538 (Print)
IS  - 0105-4538 (Linking)
VI  - 60
IP  - 8
DP  - 2005 Aug
TI  - Mutations in the high-affinity IgE receptor beta-chain are not associated with 
      nonresponder status.
PG  - 1040-5
AB  - BACKGROUND: Basophils of some individuals do not release histamine upon 
      activation of their high-affinity immunoglobulin E (IgE) receptor 
      (Fc(epsilon)RI), but do so if this receptor is circumvented for cell activation. 
      This so-called nonresponder phenomenon is clinically relevant, because in various 
      studies atopy was less frequent or absent in nonresponder individuals. So far, it 
      is unknown if this phenomenon is acquired during adulthood or exists from birth 
      on. METHODS: Histamine release was determined from isolated leucocytes stimulated 
      with anti-IgE or calciumionophor. Also, random primed cDNA was synthesized and 
      the open reading frame (ORF) of the Fc(epsilon)RI beta-subunit amplified and 
      sequenced. RESULTS: In the first part of our study, we examined the role of 
      atopic status, type of atopy, and age in a random population of 95 children of 
      whom we found 22% to be nonresponder. None of these parameters correlated with 
      the nonresponder status. Except for food allergy, no specific type of atopy 
      correlated with histamine release. The mechanism underlying the nonresponder 
      phenomenon is assumed to occur early in the signalling cascade. We hypothesized 
      that mutations in the Fc(epsilon)RI beta-chain may be associated with the 
      nonresponder status, and in the second part of our study sequenced the 
      beta-subunit in 20 responders and 20 nonresponders. Two conservative and two 
      nonconservative heterozygous one base mutations (Thr179Thr, Asp216Asp, Ile147Leu 
      and Glu237Gly) were found in two nonresponders and one responder. Three of these 
      mutations have not been described so far. CONCLUSION: The nonresponder phenomenon 
      is present from birth on and genetically determined. In our population, it was 
      not associated with age or the presence of atopy, and appeared not to be caused 
      by mutations in the Fc(epsilon)RI beta-chain.
FAU - Kuster, H
AU  - Kuster H
AD  - Department for Neonatology and Pediatric Intensive Care, University Children's 
      Hospital, Greifswald, Germany.
FAU - von Manstein, S
AU  - von Manstein S
FAU - Ruocchio-Wiglinghaus, S
AU  - Ruocchio-Wiglinghaus S
FAU - von Brunn, A
AU  - von Brunn A
FAU - Reinhardt, D
AU  - Reinhardt D
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - Denmark
TA  - Allergy
JT  - Allergy
JID - 7804028
RN  - 0 (MS4A2 protein, human)
RN  - 0 (Receptors, IgE)
SB  - IM
MH  - Age Factors
MH  - Amino Acid Sequence
MH  - Base Sequence
MH  - Binding, Competitive
MH  - Child
MH  - Female
MH  - Food Hypersensitivity/metabolism
MH  - Heterozygote
MH  - *Histamine Release
MH  - Humans
MH  - Hypersensitivity/*genetics/*metabolism
MH  - Male
MH  - Molecular Sequence Data
MH  - *Mutation
MH  - Receptors, IgE/*genetics/*metabolism
EDAT- 2005/06/23 09:00
MHDA- 2005/12/13 09:00
CRDT- 2005/06/23 09:00
PHST- 2005/06/23 09:00 [pubmed]
PHST- 2005/12/13 09:00 [medline]
PHST- 2005/06/23 09:00 [entrez]
AID - ALL807 [pii]
AID - 10.1111/j.1398-9995.2005.00807.x [doi]
PST - ppublish
SO  - Allergy. 2005 Aug;60(8):1040-5. doi: 10.1111/j.1398-9995.2005.00807.x.