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

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.

The effect of successful low-dose immunotherapy ascertained by provocation neutralization on lymphocytic calcium ion influx following electric field exposure

“…The results of this study offer support for all three hypotheses and are consistent with our previous findings [1]. Significant main effects for low-dose immunotherapy were observed for: benzoate; formaldehyde; metabisulfite; natural gas; nitrosamines; organophosphates; and salicylate.…”

“…Our present results suggest that patients may experience increased sensitivity to allergens as a result of exposure to everyday electric fields. We noted in our previous recent paper that while resting lymphocytes maintain a low cytosolic calcium ion concentration, antigen receptor signaling results in calcium ion influx, predominantly via store-operated calcium (SOC) channels, and inhibition of lymphocyte calcium ion channel expression has been found to prevent experimental asthma [1,13,14]. Our new findings may be associated with the finding that electromagnetic fields activate voltage-gated calcium ion channels; Pall has recently suggested that such activation may produce adverse effects [15,16].…”

“…We have recently shown that low-dose immunotherapy, which is a form of allergen-specific immunotherapy in which low doses of the antigen are administered intradermally or sublingually, affects 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 [1]. However, in practice, patients who suffer from chemical sensitivities are also subjected to background electric fields, for example the fluctuating electromagnetic field produced by mains electricity, which has the same frequency as that of the electricity supply (50 Hz in the United Kingdom).…”

“…While low-dose immunotherapy has been demonstrated to be effective in the treatment of food, chemical, and inhalant-particulate sensitivities [5][6][7][8], its underlying molecular mechanism of desensitization is not yet established [1]. Our recent previous study supported the possibility that this mechanism might involve reduced lymphocytic calcium ion influx but did not take into account the influence of ambient electric field exposure, which by the above argument might be expected to amplify this effect in sensitive patients [1]. There is not, however, any reason to expect that the effect of low-dose immunotherapy depends on electric field exposure.…”