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The Role of IgG and Food Sensitivity in Chronic Disease
© 1999 - Do Not Reproduce Without Authorized Permission
This independent literature review was carried out between the dates of 01/09/99 and 09/10/99
by Alison Mathery B.Sc. (Hons) Biochemistry, Ph.D. Immunology (submission in process).
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CONTENTS
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1. SUMMARY
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2. INTRODUCTION .
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3. THE CASE AGAINST IgG AND FOOD SENSITIVITY IN CHRONIC DISEASE
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4. THE CASE FOR IgG AND FOOD SENSITIVITY IN CHRONIC DISEASE
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4.1 INDEPENDENT BEHAVIOUR OF FOOD SPECIFIC IgG .
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4.2 COW’S MILK SENSITIVITY
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4.3 ECZEMA
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4.5 INFLAMMATORY BOWEL DISEASE
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4.6 IRRITABLE BOWEL SYNDROME .
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4.7 MIGRAINE
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4.4 FOOD SENSITIVITY IN ATOPY
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4.8 RHEUMATOID ARTHRITIS .
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CONCLUSIONS .
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APPENDIX I (search strategy)
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REFERENCES
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1. SUMMARY
 YNL have developed an ELISA to detect food specific IgG in the serum of individuals with
suspected food sensitivity. They have good testimonial evidence that shows that the dietary
modifications suggested by the ELISA results are very successful in providing symptomatic relief
from a variety of chronic conditions.
 The scientific literature world-wide was reviewed to find evidence for and against the role of IgG
in food sensitivity.
 The review revealed evidence to support the view that food specific IgG may indeed serve as a
useful diagnostic marker for food sensitivity related to chronic disease. However its role in the
pathogenesis of these disease conditions is less clear.
 The occurrence of raised levels of IgG in food sensitive individuals, and their decrease when the
offending food is removed from the diet, provides strong circumstantial evidence for the
involvement of IgG in food sensitivities. This view is further supported when the elimination of
offending foods also results in symptomatic improvement.
 Well designed clinical trials will be necessary to provide more convincing evidence for the role of
food specific IgG in chronic disease. YNL is currently undertaking such studies.
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2. INTRODUCTION
Over the past 2 years YNL Ltd have been conducting tests to detect raised IgG antibodies for food
sensitivities. The test is an enzyme linked immunoassay or ELISA method consisting of a panel of
food antigens, the pattern of serum IgG reactivities against these antigens is used to identify an
individual programme of dietary modifications. They have evidence that the dietary modifications
suggested are successful in providing symptomatic relief from a wide range of chronic illnesses. The
identification of food sensitivities via this method is much easier and far more convenient for both
patient and clinician than challenge/elimination diets. Until recently, a medically extracted blood
sample was required for testing, now only 50l, taken by the patient, is needed for the same test. This
is a much faster and less inconvenient method for all parties involved as the laboratory not only returns
the results of the clinical test, but also individual dietary modifications for each patient.
The role of IgE in adverse reactions to food is much more clearly defined than non-IgE responses,
so the associated diagnostic testing traditionally involves the detection of IgE antibodies by skin prick
tests and food challenge/elimination diets, (Salkie 1994). The skin tests are not well correlated with
food allergens and are only diagnostic of IgE-mediated responses. The challenge/elimination diets are
time consuming and rely heavily on the patient for both motivation and compliance, (Miller 1998).
The theory behind testing for elevated levels of food specific IgG in the diagnosis of food sensitivities
comes from the evidence that reports raised IgG titres in the serum of atopic individuals. Early studies
show that IgE is not always detected in the sera of individuals who give an inflammatory response after
skin pricking tests, however in many of these sera, IgG is observed, (Parish 1970 and Berry 1977).
Significantly elevated levels of IgG have also been observed in the serum of individuals with certain
food sensitivities (Shiner et al 1975, Dannaeus et al 1977, Berrens et al 1981, Dannaeus & Inganas
1981, Daul et al 1987, Burks et al 1988, Lilja et al 1991, Host et al 1992 and Germano et al 1993).
Adverse reactions to food can cause a range of symptoms throughout the body, which are thought
to be immunologically or non-immunologically mediated. The two immunologically related responses
differ in that food allergy (IgE mediated) usually occurs within 1 hour of ingestion and results in a
variety of symptoms involving the skin, gastrointestinal tract (GIT) and lungs. Food sensitivity
(elevated food specific IgG levels often observed) involves a delayed reaction, usually occurring
between 24 to 120 hours after eating and is more of a recurrent/ongoing response. The symptoms are
more generalised and may include bloatedness, cramps, nausea, rashes, migraine and general malaise.
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The GIT contains the largest surface area of mucosal lymphoid tissue of any organ in the body;
therefore it is the obvious choice for major antigen sensing and antibody production. The food
antigens are sampled from the contents of the GIT by immune mediators, which are capable of
recognising most of the food antigens; thus an individual is routinely sensitised to many of the foods
ingested. An immune reaction in the GIT will induce an inflammatory response, leading to increased
GIT permeability and demonstration of the associated symptoms of heartburn, nausea and vomiting.
The increased permeability of the GIT allows incompletely digested food to enter the bloodstream and
is then treated as a pathogen to be recognised by circulating antibodies, leading to the symptoms of
other organs mentioned. This continual stress will eventually cause the immune system to weaken,
leaving the individual much more susceptible to illness.
Functional experiments have provided evidence of a pathogenic role for IgG as well as IgE in food
sensitivities. IgE mediated histamine release is well documented, but other studies have shown that
IgG may also be involved, (Hindocha & Wood 1985 and Beauvais et al 1990). A study looking at the
passive transfer of milk sensitivity to non-sensitised guinea pig epithelium demonstrated an
involvement of IgG and not IgE, (Baird et al 1987). One study has shown that IgG directed antibody
dependent cell mediated cytotoxicity (mechanism where antibodies interact with cytotoxic cells) may
be of pathogenic importance in certain diseases associated with adverse GIT symptoms in cow’s milk
protein sensitive individuals. Sera from children with GIT symptoms as oppose to coeliacs patients
was shown to efficiently mediate ADCC to cells coated with -lactoglobulin. Deliberate depletion of
IgG 1, 3 and 4 caused a marked decrease in ADCC mediating capacity. Thus IgG is of pathogenic
importance in cow’s milk protein sensitive patients with GIT symptoms, (Saalman 1995).
As the theory behind testing is unclear and the reliability and validity of the test has not been fully
evaluated, this methodology is still argued against in terms of diagnostic value. Therefore, it is the aim
of this review to present evidence and key arguments in support of a role for IgG in food sensitivity.
3. THE CASE AGAINST IgG AND FOOD SENSITIVITY IN CHRONIC DISEASE
Many studies have reported food specific IgG in the serum of normal subjects, this review cites a
few examples. Food specific IgG containing immune complexes were observed in adult and children
non-atopics, (Haddad et al 1983, Paganelli et al 1983, and Lessof & Kemeny 1991). Food specific IgG
has been observed in healthy subjects (Husby et al 1985 and Kruszewski et al 1994). It has been
demonstrated by ELISA that the levels of food specific IgG in control subjects and food sensitive
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patients were not significantly different, (Portnoy et al 1988 and Burks et al 1989 and 1990). Specific
IgG was significantly raised in shrimp sensitive individuals, but the IgG response was not significantly
predictive of an adverse reaction to food challenge (Morgan et al 1990). It has been demonstrated that
food specific IgG levels don’t seem to be predictive of certain diseases such as inflammatory bowel
disease and eczema, (Zvetckenbaum 1988 and Sloper et al 1991).
4. THE CASE FOR IgG AND FOOD SENSITIVITY IN CHRONIC DISEASE
Although elevated levels of food specific IgG seems to be a good marker of food sensitivities, the
exact role played by IgG remains unclear. There is however considerable evidence that argues in
favour of the involvement of food specific IgG in individuals who suffer from adverse reactions to
foods. This includes the demonstration of an independent behaviour of food specific IgG compared to
IgE in food sensitive individuals and the observation of elevated levels of food specific IgG in various
diseases.
A search of the relevant literature associated with food sensitivity reveals evidence
supporting a role for food specific IgG in the pathogenesis of various diseases and ailments. Probably
the most common is a general sensitivity to cow’s milk producing various symptoms including those
associated with the GIT, respiratory tract and the skin.
4.1 INDEPENDENT BEHAVIOUR OF FOOD SPECIFIC IgG
In many individuals who suffer from an immunologically related adverse reaction to food, the food
specific IgG behaves independently of the IgE, suggesting that there is more than one
immunopathogenic mechanism involved, (Brighton 1980).
In orally challenged food sensitive individuals two components of the complement pathway were
utilised in the specific immune response, the IgE levels were unchanged from normal, suggesting IgG
may have triggered complement leading to inflammation, and the adverse effects, (Trevino et al 1981).
Sera from eczema patients contained high levels of milk specific IgG, A and E whereas cow’s milk
allergy patients had high levels of IgE only, indicating two possible different pathogenic mechanisms,
IgE mediated mast cell degranulation and the eczema skin lesions were probably the result of chronic
antigen exposure, leading to immune complex deposition and local inflammatory response in the skin,
(Firer et al 1982). In egg allergic individuals, elevated ovalbumin specific IgG showed no relationship
with IgE and in some patients IgG was observed in the absence of IgE, (Nakagawa 1986). Individuals
with late onset food allergies of the skin, respiratory tract and GIT mostly had elevated IgG compared
with IgE and in some a food induced IgE response was absent altogether, (el Rafei et al 1989). In food
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allergic children, 77% had elevated IgG and only 37% had IgE, in non-allergic individuals there was no
response.
Elimination and re-introduction of offending food lead to remission and relapse of
symptoms respectively, (Hoffman 1995).
These particular studies emphasise that elevated food specific IgE is not always involved in adverse
reactions to food, as there is evidence of a high occurrence of elevated IgG in association with
symptomology this suggests that there are at least two immunological mechanisms involved in the
pathogenesis of food sensitivity.
4.2 COW’S MILK SENSITIVITY
An infant with anaemia and chronic bronchitis associated with cow’s milk showed elevated levels
of cow’s milk specific IgG measured by ELISA. When milk was removed from the diet there was
symptomatic improvement and a decrease in cow’s milk IgG was observed in the absence of IgE. The
investigators hypothesised that the initial formula feeding sensitised the infant to cow’s milk protein,
which caused a slight intestinal illness leading to increased gut permeability and when whole cow’s
milk was introduced into the diet a marked immune response involving IgG occurred, (Cohen et al
1985). It has been demonstrated that anti--lactoglobulin IgG correlates well with delayed onset cow’s
milk sensitivity and that antibodies against -lactoglobulin may be useful in the diagnosis of cow’s
milk protein sensitivity, (Fallstrom et al 1986 and Shakib et al 1986). Significantly higher levels of
anti -lactoglobulin IgG were observed in infants with persistent cow’s milk allergy, (Host et al 1992).
In children from atopic families, elevated levels of cow’s milk specific IgG was detected by
enzyme immunoassay. The ingestion of milk caused significant increases in milk specific IgG in the
patients with sensitivity to cow’s milk, (Hamburger et al 1987). In a later study an ELISA designed to
detect cow’s milk protein specific IgG revealed the presence of milk specific IgG in the serum of cow’s
milk protein sensitive children. The levels of IgG were significantly higher than those found in control
individuals, which consisted of those with ‘toddler diarrhoea’, atopic individuals and normal healthy
subjects.
The ELISA was highly sensitive and specific for the diagnosis of cow’s milk protein
sensitivity when differentiating between that and general infant diarrhoea, (Taylor et al 1988). When
anti--lactoglobulin IgG levels were measured by an enzyme immunoassay, marked differences in IgG
levels were apparent in cow’s milk protein sensitive individuals compared with healthy controls and
those with GIT symptoms not associated with food sensitivity. The investigators stated that the
enzyme immunoassay test could be used to confirm the diagnosis of cow’s milk protein sensitivity,
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(Iacona et al 1995). Patients with gastroesophageal reflux (GER) plus cow’s milk sensitivity were
significantly positive for anti--lactoglobulin IgG compared with those with GER only, suggesting that
tests that detect elevated anti--lactoglobulin IgG are specific and sensitive methods for the diagnosis
of GER with cow’s milk sensitivity, (Cavataio et al 1996).
It has been shown that preferential recognition of some epitopes of an antigen can be observed for
IgG in children with cow’s milk sensitivity. Specific anti--lactoglobulin IgG specificity to native and
pepsin digested -lactoglobulin was measured by ELISA. In cow’s milk sensitive individuals there
was significant binding to the native compared with the digested -lactoglobulin, in the controls there
was no difference in binding (weak). The binding of IgG to native -lactoglobulin was significantly
higher in the sensitives compared with controls and levels of -lactoglobulin specific IgG declined
with elimination of milk from the diet, this was not the case for the healthy controls where the lowlevel IgG was independent of milk consumption. The direct relationship between levels of anti-lactoglobulin IgG and the success of elimination of milk demonstrated that milk specific IgG is a
useful indicator of food sensitivities, which may be used in dietary modifications, (Duchateau et al
1998).
4.3 ECZEMA
Eczema is a group of skin conditions in which the severity of the disease can vary, in mild forms
the skin is dry, hot and itchy, whilst in more severe forms the skin can become broken, raw and
bleeding. With treatment the inflammation of eczema can be reduced, though the skin will always be
sensitive to flare-ups and need extra care. The causes of eczema are many and varied, and depend on
the particular type of eczema that a person has. Atopic eczema is thought to be a hereditary condition,
being genetically linked. It is proposed that people with atopic eczema are sensitive to allergens in the
environment which are harmless to others. In atopy there is an excessive reaction by the immune
system producing inflamed, irritated and sore skin. Associated atopic conditions include asthma and
hayfever. Other types of eczema are caused by irritants such as chemicals and detergents, allergens
such as nickel, and yeast growths. In later years eczema can be caused by a blood circulatory problems
in the legs. The causes of certain types of eczema remain to be explained, though links with
environmental factors and stress are being explored.
It has been demonstrated that milk specific IgG is elevated in some children with milk inducing
eczema and some milk sensitive children without eczema have no IgG response. This points towards
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the fact that in milk related eczema the milk specific IgG may be involved in the pathogenic
mechanism of the disease via immune complex deposition, (Firer 1982). Milk specific IgG was found
in much higher levels in patients with food inducing eczema compared with controls. However, this
phenomenon was not observed with egg specific IgG, but the controls used in this study included just
two healthy adults and the rest were children who had been referred to the hospital for apparently nonatopic disorders, (Shakib et al 1984). In cow’s milk protein sensitive eczema patients, an ELISA
showed elevated IgG to -lactoglobulin, -lactalbumin, and -casein for all subclasses in these
patients compared with the control subjects, (Shakib et al 1986).
One investigation demonstrated significantly elevated levels of IgG against -lactoglobulin in
atopic eczema patients compared with healthy subjects, (Husby et al 1989). In patients with atopic
eczema, significant increases in IgG levels were observed with milk ingestion and the investigators
concluded that IgG should be considered when eliminating offending foods, (Iikura et al 1989).
Significantly elevated levels of IgG against egg white, egg yolk and -lactoglobulin were reported in
the sera of atopic eczema patients compared with controls, (Garcia et al 1990). In children with atopic
eczema and GIT symptoms associated with food ingestion, IgG for casein was significantly elevated,
the investigators concluded that IgG is useful in the diagnostic work-up, particularly in children with
GIT symptoms, (Lucarelli et al 1998).
From these studies it seems that elevated milk specific IgG plays an important role in the
development of some forms of eczema/dermatitis and in some cases a diagnosis can be made by
elevated IgG subclasses to cow’s milk proteins.
4.4 FOOD SENITIVITY IN ATOPY
Elevated levels of IgG have also been described in other atopic and allergic individuals. In
patients with various allergic related symptoms, elimination of food that gave a positive IgG RAST
test, resulted in a 70% reduction of symptoms. This suggests that detection of elevated food specific
IgG may be helpful in the diagnosis of food sensitivity related diseases, (Dockhorn 1987). In patients
with food induced allergies manifested in the skin, respiratory tract and GIT, late onset allergies
showed a greater IgG response compared with IgE and in some patients the IgE response was
completely absent. In most of these patients, the clinical histories matched the IgG4response, (el Rafei
et al 1989). In bakers with adverse reactions to wheat flour, levels of specific IgG by enzyme
immunoassay were significantly higher than those with no adverse reactions, (Tiikkainen & Klockars
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1990). In patients with general food sensitivities, the IgG titres by enzyme immunoassay, which far
exceeded the IgE levels measured by RAST tended to correlate well with patient history and
symptomology, (Berrens & Homedes 1991).
In atopic individuals with egg allergy over 5 years old, elevated levels of ovalbumin specific IgG
were observed compared with non-egg allergic atopic patients, (Nakagawa et al 1986). In a study that
monitored patients whilst on an elimination diet based on previous food specific IgG positivity, there
was a significant correlation in decrease of food specific IgG levels. The patients were also much
improved in their clinical symptoms, supporting the value of IgG determination to foods as a helpful
tool to reduce illness, (Marinkovich 1996). In soybean intolerants, most of the proteins giving a high
IgG response differed from the proteins giving an IgE response in the same ailments, again suggesting
that another immune mechanism involving IgG is occurring. The frequency of soybean specific IgG
was high in infants and in the latter stages of infancy it was low, suggesting that IgG is suppressed in
normal individuals and if this mechanism is altered it may have an adverse effect, thus suggesting a
role for IgG in the pathogenesis of food sensitivity in these individuals, (Awazuhara et al 1997).
4.5 INFLAMMATORY BOWEL DISEASE
Inflammatory bowel disease is a chronic disorder causing inflammation or ulceration in the small
and large intestines, the cause is unknown. There are two main types of inflammatory bowel disease:
Crohn's disease and ulcerative colitis. In Crohn's disease, the wall of the intestine becomes sore,
inflamed, and swollen. Ulcerative colitis is a condition that causes tiny sores to form in the inner
lining of the colon and rectum.
Crohn's disease and ulcerative colitis have similar symptoms:
abdominal pain and cramps, diarrhoea, and rectal bleeding and/or bloody stools. Also common are pain
in the joints, lack of appetite, weight loss, and fever. There is no test to identify the disease and
diagnosis is usually based on a medical history, a physical exam, and blood tests. In addition, patients
often undergo barium X-rays of the upper and lower gastrointestinal tract, as well as endoscopic
procedures allowing examination of the colon and rectum through a lighted instrument inserted
through the anus. Treatment involves minor adjustments to the diet (for example, a decrease in fat,
fiber, and lactose) sometimes help in decreasing symptoms, but a specially tailored diet plan may be
necessary. A number of medications are used to treat inflammatory bowel disease, including antiinflammatory drugs and antibiotics for local infections.
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The responses to dietary antigens have been implicated as playing a role in inflammatory bowel
disease (IBD). In patients with food induced enterocolitis, the antigen specific IgG response to soy and
eggs was at least 10 times higher than in control subjects, (McDonald et al 1984). Monozygotic twins
with IBD including Crohn’s disease and ulcerative colitis were studies for their IgG, IgA and IgM
responses to egg, milk, gliadin, yeast and mannan (component of yeast cell wall). The only difference
between the ulcerative colitis patients and the controls was in the response to gliadin. The Crohn’s
disease patients, however gave significantly high titres for antibodies against mannan and whole yeast.
This suggested that in Crohn’s disease, the immune system is selectively activated by an antigen in the
yeast cell wall, (Lindberg et al 1992).
4.6 IRRITABLE BOWEL SYNDROME
Food sensitivity has been implicated as playing a role in irritable bowel syndrome (IBS). Patients
with IBS have chronic symptoms of abdominal pain, bloating, and disordered bowel habits (e.g.
diarrhoea, constipation or wind) for at least 3 months per year (Thompson et al 1999). These symptoms
of functional disorder of the bowel are commonly associated with non-bowel symptoms of other
disorders such as fibromyalgia, chronic fatigue syndrome, as well as symptoms arising from pelvic
organs such as dysmenorrhoea and urinary symptoms, (Camilleri & Choi 1997). These patients have
usually been fully investigated and other pathology excluded on endoscopy and barium studies. After
being diagnosed IBS they are offered a range of treatments often aimed at suppressing symptoms such
as anti-inflammatory or anti-cholinergic agents. For many patients these are only partially successful
and only temporarily, (Camilleri & Choi 1997). IBS is associated with considerable medical costs,
(Talley et al, 1995), accounting for approximately 10% of the workload of general practitioners, (Jones
1996). The cause of IBS is unknown, indeed it is not clear whether it is in fact a single clinical entity
or a convenient label for patient with chronic functional bowel disorder of varying origin, (Shaw et al
1998).
The role of food in the aetiology of IBS is controversial e.g. a common recommendation for
patients with IBS is to increase bran consumption, (Harvey et al 1987). This advice is based on the
theory that IBS is caused by lack of fibre in the diet, (Painter 1972). Minimal evidence exists that bran
has therapeutic value in this disorder, (Lynn & Freidman 1993). However, a recent trial has shown that
bran supplementation is of no value in relieving the symptoms of IBS, (Snook & Shepherd 1994). It
has also been shown that bran may increase these symptoms and is possibly responsible for
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exacerbating mild, non-complaining cases, thereby creating more IBS patients, (Francis & Whorwell
1994).
There is evidence that IBS may (at least in some patients) be the result of food sensitivity, (AlunJones et al 1992, Fell et al 1991 and Bischoff et al 1996). Recently, a systematic review of the
literature using Medline (1980-1996), targeting IBS and adverse reactions to food was conducted. Out
of 32 publications located, a total of 7 fulfilled the inclusion criteria, (written in English, adult subjects,
no letters/abstracts). The studies included were Jones et al 1982, Bentley et al 1983, Farah et al 1985,
Petitpierre et al 1985, McKee et al 1987, Zwetckenbaum & Burakoff 1988 and Nanda et al 1989. Of
these studies, the positive response to an elimination diet ranged from 15-71% and double-blind
placebo-controlled food challenges identified problem foods in 6-58% of cases. However, all selected
studies had major limitations in their trial designs including inadequate patient selection,
appropriateness and duration of elimination diets, and methods of food challenge. Carefully designed
controlled clinical trials are necessary to test the role of adverse reactions to food in patients with IBS,
(Niec et al 1998).
Food specific IgG has been observed in patients with GIT symptoms (Iacona et al 1995, Cavataio
et al 1996) and in patients with more clinically defined gastrointestinal diseases. In gluten-sensitive
enteropathy both IgG and IgA antibodies to gliadin, as well as other dietary antigens have been well
documented in relation to coeliac disease, (Unsworth et al 1983 and O’Farrelly et al 1983). Recently,
a disease like antibody pattern was also found in approximately one third of IBS patients, indicating a
potential coeliac-like disease in a subgroup of IBS patients, (Wahnschaffe et al 1998).
4.7 MIGRAINE
Patients with migraine have chronic symptoms of headache lasting from 4 to 72 hours with
transient sensory and/or gastrointestinal disturbances, (Soloman & Price 1997). Migraine is not
associated with considerable medical costs, which is largely due to low rates of consultation by
sufferers and poor of recognition of the disorder by physicians.
Population-based studies have
demonstrated that 19 to 44% of the patients never consult a doctor, furthermore, most sufferers who
initially consult a GP rarely go back, (Stang et al 1994, Lipton et al 1995).
The low rate of
consultation may be due to poor initial diagnosis and that most migraine sufferers rely on over-thecounter medication rather than being treated with prescription drugs, thus, may not be receiving
effective treatment. Although migraine isn’t associated with high medical costs, its impact on quality
of life is considerable and has economic implications in terms of productivity losses due to disrupted
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work. The overall cost attributable to migraine is unknown, but it is established that the indirect costs
outweigh the direct medical costs and represent an obvious target for intervention aimed at reducing
the impact of this chronic condition.
The cause of migraine is still largely unknown, however, there is evidence that it may result from
food sensitivity, about 25% of migraine patients report that their symptoms can be initiated by certain
foods, (van den Bergh et al 1987). A double blind study on 40 migraine affected children, reported a
decrease of attacks with the avoidance of some foods. Associated symptoms also improved including
abdominal pain, fits, asthma and eczema (Egger et al 1983). Other studies have observed a decrease in
number of attacks in 80% of patients on avoidance diets, (Hughes et al 1985 and Mansfield et al 1985).
A role for IgG in the induction of migraine has been proposed but not confirmed, (Lord & Duckworth
1977 and Jerzmanovski & Klimek 1983).
4.8 RHEUMATOID ARTHRITIS
Rheumatoid arthritis is an inflammatory disease that causes pain, swelling, stiffness, and loss of
function in the joints. It can also affect other parts of the body besides the joints and people with the
disease may have fatigue, occasional fever, and a general sense of malaise. The severity of the disease
ranges from mild or moderate to severe disease that is active most of the time, lasts for many years, and
leads to serious joint damage and disability.
There is no treatment that can cure or reverse rheumatoid arthritis, however, there are medications
that can relieve its symptoms and slow or halt its progression. They include nonsteroidal antiinflammatory drugs (help relieve pain and inflammation), corticosteroids (reduce inflammation and
slow joint damage), disease-modifying antirheumatic drugs (slow or halt the progression of rheumatoid
arthritis).
Each of these treatments produce side effects including stomach upset/bleeding, easy
bruising, thinning of bones, cataracts, weight gain, diabetes, high blood pressure, blurry vision and
increased susceptibility to infection.
There have been reports that suggest adverse reactions to food may influence the disease
progression of rheumatoid arthritis in certain individuals. 9% of a group of RA patients showed a
favourable response to diet restriction and a marked exacerbation on re-challenge, six of these patients
were studied via placebo controlled re-challenges and food intolerance was observed in four of them.
This suggests a subgroup of RA in which food intolerance influences disease activity, (van der Laar &
der Korst 1992 and van der Laar et al 1992).
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5. CONCLUSION
It was the aim of this review to present evidence and key arguments supporting the role of IgG in
food sensitivity. The main reason for this is the fact that the theory behind testing is unclear and the
reliability and validity of the food specific IgG test has not been fully evaluated. For these reasons, the
diagnostic value of the methodology has been argued against.
The key argument against the role of IgG in food sensitivity is the various reports of the
presence of food specific IgG in normal healthy individuals. There are more publications opposing the
role of IgG in food sensitivity, but these studies are based on the presence of food specific IgG in
health as well as disease and not on IgG in chronic disease. In some of these studies either there is no
mention of the number of subjects used, or a low number was used so it is difficult to say how
significant the results are. Some of the studies did not reflect a sufficiently large sample of the
population.
For example, infants as normal individuals may not be accurate as it has been
demonstrated that there is an age trend increase in food specific IgG in 5-12 month old infants, which
declines to negligible levels in adults, (Ahmed et al 1997). In other studies it is unclear whether the
controls were healthy or merely non-atopic/food-challenge negative patients. In many of the studies,
different assay techniques are used and could easily give different results. Even in the same assay
technique, such as ELISA, there are many variables involved, which can produce contrasting results.
This review has been successful in providing some evidence that food specific IgG may indeed
have a role to play as a useful diagnostic marker in food sensitivity influenced chronic disease. From
the evidence, it seems that although the pathogenic mechanism of food sensitivity is unclear, IgG is
involved in some way. Its occurrence in raised levels in food sensitive individuals, and its decrease
when the offending food is removed from the diet provides strong evidence of its involvement. This is
especially true when the elimination of offending food results in symptomatic improvement. However,
the lack of studies looking at the mechanism of IgG in food sensitivity and clinical trials involving a
disease group such as irritable bowel syndrome, migraine and eczema make it impossible to say for
certain that the food specific IgG is the cause of some of the chronic diseases discussed.
At the present time the evidence suggests that the testing for food specific IgG by the reliable and
reproducible ELISA technique may be of use as a diagnostic tool, which can be utilised to reduce or
remove the adverse symptoms of many individuals who suffer from food sensitivity. Clinical trials
involving disease groups and healthy individuals, along with double blind placebo controlled
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elimination diets in conjunction with the food specific IgG test, will be helpful in providing more
convincing evidence that IgG has a role to play in the pathogenesis of certain diseases associated with
food sensitivity.
APPENDIX I - Search strategy
The scientific literature databases searched were MEDLINE (1966-1999), BIDS (1981-1999) and
AGRICOLA (1979-1999). Key words used were food sensitivity, food intolerance and food allergy.
Variations on these searches included one of the above plus IgG, immunoassay/ELISA,
immunopathogenesis/pathogenesis or diagnostic tests.
The search results were incorporated and
merged in Endnotes reference management software to give over 7000 references some of which were
not related to this study and were deleted to give about 6000 references. IgG was then used as the key
word to give 231 references, the abstracts of each were read if available and 88 relevant papers were
chosen to be included in this review.
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