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Higher plasma concentration of food-specific antibodies in persons with autistic disorder in comparison to their siblings во трудот Clinical Usefulness of IgG Food Allergy Testing од страна на д-р William Shaw директор на Greаt Plains Laboratory од САД. Ви го проследувам трудот во целост, а нашата референца е под реден број 10.
Извор: http://www.greatplainslaboratory.com/articles-1/
Immunoglobulin G (IgG) food allergy
testing has made vast advancements since the year 2003 when the American
Academy of Allergy, Asthma, and Immunology published a statement that
"Measurement of specific IgG antibodies to foods is also unproven as a
diagnostic tool"(1) Most of the IgG food allergy throughout the world is
done using the same immunochemical technique. First, soluble food
proteins in solution are reacted to a solid phase that chemically binds
to a variety of proteins. The use of plastic microtiter trays with one
to several hundred wells has become the most common material used as the
solid phase. Then these trays are washed, dried, and stored for later
use. A sample of diluted serum is then added to each of the wells.
Antibodies of all types in the diluted serum bind to the specific food
molecules that are attached to the plastic wells of the tray. Next, the
plates are washed to remove any nonspecific antibodies in the diluted
serum. At this time, food antibodies from all of the five major
immunoglobulin classes called G, A, M, E, and D may be attached to the
food antigens on the plate. The next step confers specificity on the
assay. Antisera from sheep, goats, rabbits, or other animals that
specifically binds to IgG is added to microtiter wells and only binds to
IgG, not to IgA, IgM, IgE, or IgD. This antibody to IgG has previously
been modified by the attachment of an enzyme that can be measured
conveniently. The amount of enzyme bound to food antigen-IgG complexes
on the plate is directly related to how much IgG antibody is attached to
a given food. The overall technique is termed Enzyme Linked Immuno
Assay or ELISA. If IgG4 is measured, an antiserum specific for IgG4 only
must be used for the final step.
The
clinical usefulness of IgG testing in an array of illnesses is
illustrated in an early article published by an otolaryngologist who
reported that the majority of his patients had substantial health
improvements after an elimination of foods positive by IgG food allergy
tests (2). The overall results demonstrated a 71% success rate for all
symptoms achieving at least a 75% improvement level. Of particular
interest was the group of patients with chronic, disabling symptoms,
unresponsive to other intensive treatments. Whereas 70% obtained 75% or
more improvement, 20% of these patients obtained 100% relief. Symptoms
most commonly improved 75%-100% on the elimination diets included
asthma, coughing, ringing in the ears, chronic fatigue, all types of
headaches, gas, bloating, diarrhea, skin rash and itching, and nasal
congestion. The most common IgG food allergies were cow's milk, garlic,
mustard, egg yolk, tea, and chocolate.
The
usefulness of IgG food allergy to design customized elimination diets
has now been documented in scientific studies. Irritable bowel syndrome
(IBS) is a common, costly, and potentially disabling gastrointestinal
(GI) disorder characterized by abdominal pain/discomfort with altered
bowel habits (e.g., diarrhea, constipation). The major symptoms of IBS
are (1) abnormality of bowel movement, (2) reduction in bowel
sensitivity thresholds, and (3) psychological abnormality. Many IBS
patients have psychological symptoms including depression, anxiety,
tension, insomnia, frustration, hypochondria. psychosocial factors (3).
Atkinson et al (4)evaluated a total of 150 outpatients with irritable
bowel syndrome (IBS) who were randomized to receive, for three months,
either a diet excluding all foods to which they had raised IgG
antibodies (ELISA test) or a sham diet excluding the same number of
foods but not those to which they had antibodies . Patients on the diet
dictated by IgG testing had significantly less symptoms than those on
the sham diet after 120 days on the diets. Patients who adhered closely
to the diet had a marked improvement in symptoms while those with
moderate or low adherence to the IgG test dictated diets had poorer
response. Similar results were also obtained by Drisko et al (5). They
used both elimination diet and probiotic treatment in an open label
study of 20 patients with irritable bowel syndrome diagnosed at a
medical school gastroenterology department. The most frequent positive
serologic IgG antigen-antibody complexes found on the food IgG tests
were: baker's yeast, 17 out of 20 (85%); onion mix, 13 out of 20 (65%);
pork, 12 out of 20 (60%); peanut 12 out of 20 (60%); corn, 11 out of 20
(55%);wheat, 10 out of 20 (50%); soybean, 10 (50%); carrot, 9 out of 20
(45%); cheddar cheese, 8 out of 20 (40%); egg white, 8 out of 20 (40%).
Only 5 out of 20 reacted by IgG antibody production to dairy; however
the majority of patients reported eliminating dairy prior to trial
enrollment presumably clearing antigen-antibody complexes prior to
testing. Significant improvements were seen in stool frequency, pain,
and IBS quality of life scores. Imbalances of beneficial flora and
dysbiotic flora were identified in 100% of subjects by comprehensive
stool analysis. There was a trend to improvement of beneficial flora
after treatment but no change in dysbiotic flora. The one-year follow up
demonstrated significant continued adherence to the food rotation diet,
minimal symptomatic problems with IBS, and perception of control over
IBS. The continued use of probiotics was considered less helpful.
IgG
food allergy testing was also proved effective in the gastrointestinal
disorder Crohn's disease. Bentz et al (6) found that an elimination diet
dictated by IgG food allergy testing resulted in a marked reduction of
stool frequency in a double blind cross-over study in which the
IgG-dictated diet was compared to a sham diet in 40 patients with
Crohn's disease. IgG food allergies were significantly elevated compared
to normal controls. Cheese and baker's yeast (Saccharomyces cerevisiae)
allergies were extremely common with rates of 83% and 84% respectively.
Main et al (7), focusing on the baker's yeast allergy, also found
extremely high prevalence of IgG allergy in patients with Crohn's
disease. Titers of both IgG and IgA to S. cerevisiae in the patients
with Crohn's disease were significantly higher than those in the
controls. In contrast, antibody titers in the patients with ulcerative
colitis were not significantly different from those in the controls.
Among the patients with Crohn's disease there was no significant
difference in antibody titers between patients with disease of the small
or large bowel. Since IgG antibodies to S. cerevisiae cross react with
Candida albicans (8), Candida species colonization might be a trigger
for the development of Crohn's disease.
IgG
food allergy to wheat, gluten, gliadin, rye, and barley are prevalent
in the gastrointestinal disorder celiac disease. Virtually all patients
with celiac disease have elevated IgG antibodies to gliadin if they
currently have wheat or related grains in their diet. The confirmation
of celiac disease is confirmed by the presence of flattened mucosa with a
lack of villi when a biopsy sample of the small intestine is examined
microscopically. Another confirmation test with equal sensitivity is a
blood test for IgA transglutaminase antibodies. The antibody
confirmation test is equal in accuracy to the biopsy test with the
exception that individuals with IgA deficiency may have false negative
results. However, I would estimate that only 1% of people with elevated
IgG antibodies to gliadin and other grains related to wheat have celiac
disease. If the individual is negative for the confirmation tests for
celiac disease, many patients are frequently erroneously advised that
that have no problem with wheat. Hadjivassiliou et al argued that it is a
significant clinical error to classify wheat allergy through the filter
of celiac disease (9) and argue that celiac disease is a subtype of
wheat sensitivity. Many of their patients with wheat allergy but celiac
disease negative had remission of severe neurological illnesses when
they adopted a gluten free diet and expressed that in these patients the
gluten molecule causes an autoimmune reaction in the brain rather than
in the intestinal tract, likely against the Purkinje cells that are
predominant in the cerebellum.
A
wide range of additional studies has proven the clinical value of IgG
antibodies in autism (10), bipolar depression (11), schizophrenia (12),
migraine headaches (13), asthma (14), and obesity (15).
Total IgG Versus IgG4 Food Allergy
Immunoglobulin
G (IgG) is classified into several subclasses termed 1, 2, 3, and 4.
IgGs are composed of two heavy chain–light chain pairs (half-molecules),
which are connected via inter–heavy chain disulfide bonds situated in
the hinge region (Figure 1). IgG4 antibodies usually represent less than
6% of the total IgG antibodies. IgG4 antibodies differ functionally
from other IgG subclasses in their lack of inflammatory activity, which
includes a poor ability to induce complement and immune cell activation
because of low affinity for C1q (the q fragment of the first component
of complement). Consequently, IgG4 has become the preferred subclass for
immunotherapy, in which IgG4 antibodies to antigens are increased to
reduce severe antigen reactions mediated by IgE. If antigens
preferentially react with IgG4 antibodies, the antigens cannot react
with IgE antibodies that might cause anaphylaxis or other severe
reactions. Thus, IgG4 antibodies are often termed blocking antibodies.
Another property of blood-derived IgG4 is its inability to cross-link
identical antigens, which is referred to as "functional monovalency".
IgG4 antibodies are dynamic molecules that exchange half of the antibody
molecule specific for one antigen with a heavy-light chain pair from
another molecule specific for a different antigen, resulting in
bi-specific antibodies that are unable to form large cross-linked
antibodies that bind complement and thus cause subsequent
inflammation(16). In specific immunotherapy with allergen in allergic
rhinitis, for example, increases in allergen-specific IgG4 levels indeed
correlate with improved clinical responses. IgG4 antibodies not only
block IgE mediated food allergies but also block the reactions of food
antigens with other IgG subclasses, reducing inflammatory reactions
caused by the other IgG subclasses of antibodies to food antigens.
In
IgG mediated food allergy testing, the goal is to identify foods that
are capable of causing inflammation that can trigger a large number of
adverse reactions. IgG1, IgG2, and IgG3 all are capable of causing
inflammation because these antibodies do not exchange heavy and light
chains with other antibodies to form bispecific antibodies. Thus, IgG1,
IgG2, and IgG3 antibodies to food antigens can and do form large immune
complexes or lattices that fix complement and increase inflammation. The
presence of IgG4 antibodies to food antigens indicates the presence of
antibodies to foods that will not usually cause inflammation even though
high amounts of these antibodies do indicate the presence of immune
reactions against food antigens. Testing only for IgG4 antibodies in
foods limits the ability of the clinician to determine those foods that
are causing significant clinical reactions that are affecting their
patients. The importance of measuring other subtypes of IgG antibodies
is highlighted in an article by Kemeny et al. (17). They found that IgG1
antibodies to gluten were elevated in all 20 patients with celiac
disease but none of the patients had elevated IgG4 antibodies to gluten.
Clinical References
1.
Statement of the AAAAI Work Group Report: Current Approach to the
Diagnosis and Management of Adverse Reactions to Foods, October 2003.
http://www.aaaai.org/ask-the-expert/usefulness-of-measurements-of-IgG-antibody.aspx
(Accessed October 27,2013).
2. Dixon H, Treatment of delayed
food allergy based on specific immunoglobulin G RAST testing relief.
Otoloryngol Head Neck Surg 2000;123:48-54.
3. Nagisa Sugaya N
and Nomura S, Relationship between cognitive appraisals of symptoms and
negative mood for subtypes of irritable bowel syndrome. BioPsychoSocial
Medicine 2008;2:9-14
4.Atkinson, W et al. Food elimination based
on IgG antibodies in irritable bowel syndrome: a randomised controlled
trial Gut 2004;53:1459-1464
5. Drisko J, Bischoff B, Hall M,
McCallum R, Treating Irritable Bowel Syndrome with a Food Elimination
Diet Followed by Food Challenge and Probiotics. Journal of the American
College of Nutrition 2006; 25: 514–522
6. Bentz S, et al.
Clinical relevance of IgG antibodies against food antigens in Crohn's
disease: a double-blind cross-over diet intervention study. Digestion.
2010;81:252-64.
7.Janice Main, Hamish McKenzie, Grant R Yeaman,
Michael A Kerr, Deborah Robson, Christopher R Pennington, David Parratt
Antibody to Saccharomyces cerevisiae (bakers' yeast) in Crohn's disease
BMJ 1988;297:1105-1106
8. Thomas Schaffer, Stefan Mueller, ,
Beatrice Flogerzi, , Beatrice Seibold-Schmid,Alain M. Schoepfer, and
Frank Seibold Anti-Saccharomyces cerevisiae Mannan Antibodies (ASCA) of
Crohn's Patients Crossreact with Mannan from Other Yeast Strains, and
Murine ASCA IgM Can Be Experimentally Induced with Candida albicans
Inflamm Bowel Dis 2007;13:1339 –1346
9. M Hadjivassiliou, R A
Grünewald, G A B Davies-Jones Gluten sensitivity as a neurological
illness. Neurol Neurosurg Psychiatry 2002;72:560–563
10.
Vladimir T et al Higher Plasma Concentration of Food-Specific Antibodies
in Persons With Autistic Disorder in Comparison to Their Siblings.
Focus Autism Other Dev Disabl 2008; 23: 176-185
11. Severance EG et al Immune activation by casein dietary antigens in bipolar disorder. Bipolar Disord 2010;12: 834–842
12.
Severance EG, et al Subunit and whole molecule specificity of the
anti-bovine casein immune response in recent onset psychosis and
schizophrenia. Schizophr Res. 2010;118:240-7.
13.Huber A, et al
Diet restriction in migraine, based on IgG against foods: a clinical
double-blind, randomised, cross-over trial. Int Arch Allergy Immunol.
1998; 115:67-72.
14.Vance G. et al. Ovalbumin specific
immunoglobulin G and subclass responses through the first five years of
life in relation to duration of sensitization and the development of
asthma. Clia Exp Allergy 2004;34:1452-1459
15.Wilders-Truschnig M
et al. IgG Antibodies Against Food Antigens are Correlated with
Inflammation and Intima Media Thickness in Obese Juveniles. Exp Clin
Endocrinol Diabetes 2008;116:241-5.
16. Marijn van der Neut
Kolfschoten, et al Anti-Inflammatory Activity of Human IgG4 Antibodies
by Dynamic Fab Arm Exchange. Science 2007;317:1554-1555
17.
Kemeny DM, et al Sub-class of IgG in allergic disease. I. IgG sub-class
antibodies in immediate and non-immediate food allergy. Clin Allergy.
1986; 16:571-81.
