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Desensitization to chemical and food sensitivities by low-dose immunotherapy ascertained by provocation neutralization is associated with reduced influx of calcium ions into lymphocytes.

Abstract Background Food and chemical sensitivities have detrimental effects on health and the quality of life. The natural course of such sensitivities can potentially be altered through various types of allergen-specific immunotherapy, including low-dose immunotherapy. The molecular mechanism by which low-dose immunotherapy causes desensitization has not thus far been elucidated. While resting lymphocytes maintain a low cytosolic calcium ion concentration, antigen receptor signaling results in calcium ion influx, predominantly via store-operated calcium channels. We therefore hypothesized that desensitization by low-dose immunotherapy is associated with reduced influx of calcium ions into lymphocytes. The aim of this study was to test this hypothesis. Methods Intracellular lymphocytic calcium ion concentrations were assayed in a total of 47 patients, following incubation with picogram amounts of the test allergens, using a cell-permeable calcium-sensing ratiometric fluorescent dye and fluorescence spectroscopy, both at baseline and following successful provocation neutralization treatment with low-dose immunotherapy. Results Low-dose immunotherapy was associated with a reduction in lymphocytic intracellular calcium ion concentration following treatment of: 23 % for metabisulfite sensitivity (p<0.0004); 12 % for salicylate sensitivity (p<0.01); 23 % for benzoate sensitivity (p<0.01); 30 % for formaldehyde sensitivity (p<0.0001); 16 % for sensitivity to petrol exhaust (p<0.003); 16 % for natural gas sensitivity (p<0.001); 13 % for nickel sensitivity (p<0.05); 30 % for sensitivity to organophosphates (p<0.01); and 24 % for sensitivity to nitrosamines (p<0.05). Conclusions Low-dose immunotherapy may affect baseline levels of intracellular calcium in lymphocytes, supporting the premise that allergens affect cell signaling in immune cells and provocation neutralization immunotherapy helps to promote more normal immune cell signaling.
PMID
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Authors

Mayor MeshTerms

Allergens

Desensitization, Immunologic

Keywords

allergy

calcium signaling

immunotherapy

lymphocyte activation

Journal Title journal of complementary & integrative medicine
Publication Year Start




PMID- 28731314
OWN - NLM
STAT- MEDLINE
DCOM- 20180418
LR  - 20180418
IS  - 1553-3840 (Electronic)
IS  - 1553-3840 (Linking)
VI  - 14
IP  - 2
DP  - 2017 Apr 26
TI  - Desensitization to chemical and food sensitivities by low-dose immunotherapy
      ascertained by provocation neutralization is associated with reduced influx of
      calcium ions into lymphocytes.
LID - 10.1515/jcim-2016-0010 [doi]
LID - /j/jcim.2017.14.issue-2/jcim-2016-0010/jcim-2016-0010.xml [pii]
AB  - Background Food and chemical sensitivities have detrimental effects on health and
      the quality of life. The natural course of such sensitivities can potentially be 
      altered through various types of allergen-specific immunotherapy, including
      low-dose immunotherapy. The molecular mechanism by which low-dose immunotherapy
      causes desensitization has not thus far been elucidated. While resting
      lymphocytes maintain a low cytosolic calcium ion concentration, antigen receptor 
      signaling results in calcium ion influx, predominantly via store-operated calcium
      channels. We therefore hypothesized that desensitization by low-dose
      immunotherapy is associated with reduced influx of calcium ions into lymphocytes.
      The aim of this study was to test this hypothesis. Methods Intracellular
      lymphocytic calcium ion concentrations were assayed in a total of 47 patients,
      following incubation with picogram amounts of the test allergens, using a
      cell-permeable calcium-sensing ratiometric fluorescent dye and fluorescence
      spectroscopy, both at baseline and following successful provocation
      neutralization treatment with low-dose immunotherapy. Results Low-dose
      immunotherapy was associated with a reduction in lymphocytic intracellular
      calcium ion concentration following treatment of: 23% for metabisulfite
      sensitivity (p&lt;0.0004); 12% for salicylate sensitivity (p&lt;0.01); 23% for benzoate
      sensitivity (p&lt;0.01); 30% for formaldehyde sensitivity (p&lt;0.0001); 16% for
      sensitivity to petrol exhaust (p&lt;0.003); 16% for natural gas sensitivity
      (p&lt;0.001); 13% for nickel sensitivity (p&lt;0.05); 30% for sensitivity to
      organophosphates (p&lt;0.01); and 24% for sensitivity to nitrosamines (p&lt;0.05).
      Conclusions Low-dose immunotherapy may affect baseline levels of intracellular
      calcium in lymphocytes, supporting the premise that allergens affect cell
      signaling in immune cells and provocation neutralization immunotherapy helps to
      promote more normal immune cell signaling.
FAU - Puri, Basant K
AU  - Puri BK
FAU - Howard, John McLaren
AU  - Howard JM
FAU - Monro, Jean A
AU  - Monro JA
LA  - eng
PT  - Clinical Trial
PT  - Journal Article
PL  - Germany
TA  - J Complement Integr Med
JT  - Journal of complementary &amp; integrative medicine
JID - 101313855
RN  - 0 (Allergens)
RN  - 0 (Benzoates)
RN  - 0 (Natural Gas)
RN  - 0 (Nitrosamines)
RN  - 0 (Organophosphates)
RN  - 0 (Salicylates)
RN  - 0 (Vehicle Emissions)
RN  - 1HG84L3525 (Formaldehyde)
RN  - 7OV03QG267 (Nickel)
RN  - SY7Q814VUP (Calcium)
SB  - IM
MH  - Adult
MH  - *Allergens
MH  - Benzoates/adverse effects
MH  - Calcium/*metabolism
MH  - *Desensitization, Immunologic
MH  - Environmental Illness/metabolism/*therapy
MH  - Female
MH  - Food Hypersensitivity/metabolism/therapy
MH  - Formaldehyde/adverse effects
MH  - Humans
MH  - Lymphocytes/*metabolism
MH  - Male
MH  - Multiple Chemical Sensitivity/metabolism/therapy
MH  - Natural Gas/adverse effects
MH  - Nickel/adverse effects
MH  - Nitrosamines/adverse effects
MH  - Organophosphates/adverse effects
MH  - Salicylates/adverse effects
MH  - Vehicle Emissions
OTO - NOTNLM
OT  - allergy
OT  - calcium signaling
OT  - immunotherapy
OT  - lymphocyte activation
EDAT- 2017/07/22 06:00
MHDA- 2018/04/19 06:00
CRDT- 2017/07/22 06:00
PHST- 2016/01/23 00:00 [received]
PHST- 2017/03/24 00:00 [accepted]
PHST- 2017/07/22 06:00 [entrez]
PHST- 2017/07/22 06:00 [pubmed]
PHST- 2018/04/19 06:00 [medline]
AID - 10.1515/jcim-2016-0010 [doi]
AID - /j/jcim.2017.14.issue-2/jcim-2016-0010/jcim-2016-0010.xml [pii]
PST - ppublish
SO  - J Complement Integr Med. 2017 Apr 26;14(2). pii:
      /j/jcim.2017.14.issue-2/jcim-2016-0010/jcim-2016-0010.xml. doi:
      10.1515/jcim-2016-0010.