COW'S MILK ALLERGY Clinical Trial
Official title:
Study of the Immunoreactivity of Native and Polymerized Beta-lactoglobulin in Children and Adults With Cow's Milk Allergy and/or Intolerance
Bovine β-lactoglobulin (Bos d 5) is an allergen from cow's milk with relevance to human health. We employed β-lactoglobulin polymerized using microbial transglutaminase as a model of study to identify whether protein polymerization could reduce in vivo allergenicity and maintain in vitro and ex vivo immunoreactivity for the purpose of producing a suitable molecule for use in tolerance-induction protocols. Based on previous protocols applied in mice and children, we performed in vivo challenges (using a skin prick test) with native and polymerized β-lactoglobulin in adult patients with an IgE-mediated allergy to Bos d 5. In vitro humoral immunoreactivity was analyzed using immunoblotting. Cell-mediated immunoreactivity was analyzed using ex vivo challenges with native and polymerized β-lactoglobulin monitored by leukocyte adherence inhibition tests. The study hypothesis is to identify a decrease on beta-lactoglobulin immunoreactivity after polymerization.
Cow's milk allergy is a debilitating condition of difficult diagnosis and, until the moment,
without a definitive solution that can be presented to the patient by the medical attendant.
Amongst the dozens of proteins of the cow's milk, the beta-lactoglobulin (Bos d 5) is one of
most allergenic for the fact that it is not produced by the human being and because of its
hard digestibility. The allergenicity of beta-lactoglobulin in human beings is a subject
well studied but little is known about the allergenicity of bioprocessed proteins as the
polymerized beta-lactoglobulin.
The objective of the present work is to study the immunoreactivity of the polymerized
beta-lactoglobulin and to compare it with the immunoreactivity of the native
beta-lactoglobulin in patients with and without clinical diagnosis of
hypersensitivity/intolerance to cow's milk. It was used thermically induced polymerization
and polymerization induced by transglutaminase in presence of cystein.
Five groups of patients (three symptomatic and two controls) proceeding from two clinics of
distinct characteristics had been studied according to presentation of the symptoms and
submitted to allergic cutaneous tests and immunoassays for research of specific-IgE against
beta-lactoglobulin, as well evaluation of cell-mediated immunoreactivity by challenge tests
monitored by Leukocyte Adherence Inhibition Test.
Side to side cutaneous tests with native and polymerized beta-lactoglobulin in 56 adults
with problematic hypersensibility to cow's milk previously diagnosed as intolerants to the
lactose had been carried through, as well research of specific-IgE against
beta-lactoglobulin by ImmunoCAP and immunoblot. A control group of 20 subjects tolerant to
cow's milk people with absence of specific-IgE against beta-lactoglobulin (detectable by
ImmunoCAP or by allergic skin tests) had been selected for control of the technique of
immunoblot. The results had shown that the analytical detection by immunoblot of
specific-IgE is significantly more sensible when the polymerized beta-lactoglobulin is used
in the immunoassay instead of the beta-lactoglobulin monomer. The results had shown that the
research of specific-IgE by immunoCAP below of the detection limits, or the absence of
cutaneous reactivity does not discard the possibility of IgE-mediated hypersensitivity as
demonstrated by immunoblot.
Side to side cutaneous tests with native and polymerized beta-lactoglobulin had been carried
through in 22 symptomatic children, with confirmed by ImmunoCAP diagnosis of IgE-mediated
allergy to beta-lactoglobulin. A matched control group of 22 asymptomatic children with not
detectable specific-IgE for beta-lactoglobulin by ImmunoCAP was established for comparison
of the technique of the skin tests. The results had shown that the cutaneous reactions
carried through with the polymerized beta-lactoglobulin had been significantly lesser that
the reactions of the cutaneous reactions carried through with the native beta-lactoglobulin.
The cell-mediated immunoreactivity was studied on 49 atopic subjects by paired ex vivo
allergen challenges monitored by the leukocyte adherence inhibition test. The results did
not shown significant difference between the immunoreactivity against native versus
polymerized beta-lactoglobulin.
The polymerization of proteic antigens is a promising study model to be further investigated
as a potential tool for the therapeutical induction of immunotolerance to alimentary
proteins, because it decreases the in vivo immunoreactivity and does not destroy the
allergenic epitopes as demonstrated by the in vitro and ex vivo assays .
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Observational Model: Case Control, Time Perspective: Cross-Sectional
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