Antibody combinations
One study comparing raised levels of IgE, IgG4 and double blind food challenge found that elevation of any one immuno-globulin (Ig) sub-class correlated with a positive history of food hypersensitivity in only 63% of patients, but that the combination of IgE and IgG4 correlated in 91% of patients. These high specificities have been reproduced elsewhere also with IgE and IgG food specific antigens in combination.
IgG, Crohn’s and IBS
Our group has shown that there are increased levels of food specific IgG antibodies in Crohn’s disease compared to controls (in the people in the study with Crohn’s Disease compared to the ‘control’ participants who did not have the disease). There was no significant
correlation between food antibodies and patient reported
sensitivity, possibly a result of the small number of patients in this study. These results suggest further experiments to investigate whether IgG antibodies can predict foods that provoke disease on double blind, placebo-controlled food challenge and conversely, whether specific food avoidances based on antibody titres (tested levels) might be worthwhile.
In the setting of IBS, an exclusion diet guided by the presence of IgG food-specific antibodies gave greater symptom relief and global rating scores as compared to a sham exclusion diet which did not avoid the foods indicated on IgG testing. Examining the patterns of IgG4 food-specific antibody positivity in patients with IBS compared with controls, it is apparent that subjects with IBS have significantly higher titres (tested levels) of antibodies to wheat, beef, pork and lamb than controls. An exclusion diet based on these IgG4 titres, significantly improves IBS symptoms and rectal sensitivity and compliance.
Challenge to dogma
These findings challenge the dogma that IgG antibodies to food are non-specific and of no relevance to gastroinstestinal (GI) disease. The possibility exists that IgG antibodies to food could be useful in guiding dietary management of other GI disease responsive to dietary manipulation, in particular Crohn’s disease.
IBS is often associated with adverse reactions to food and food allergy might be a mechanism for symptoms in a subgroup of these patients. The observation that faecal IgE levels are increased in a subgroup of patients with IBS but not in healthy subjects lends weight to the concept that allergy might be relevant in at least some patients with IBS.
Research findings
Investigation into the role of food intolerance in IBS dates back to 1982 when Jones et al. evaluated 25 consecutive IBS patients with a one-week elimination diet followed by open challenge with suspected foods. Of patients taking part, 67% had a resolution of symptoms. Wheat, corn, dairy products, coffee, tea and citrus were the most commonly implicated foodstuffs. Since then several studies of dietary exclusion have been reported, with response rates ranging from 15-71%. The most favourable symptomatic response in these studies of dietary manipulation has been in the sub-group with diarrhoea-predominant IBS.
The correlation of a positive dietary challenge with immunological markers of hyper-sensitivity (Type 1, IgE food allergy) has been poor. Three of the above studies examined the association between a positive dietary challenge and skin prick tests and/or radioallergosorbent (RAST) tests. One of these studies demonstrated a positive correlation in those IBS patients with a history of atopy (suffering from allergy) only.
Additional indirect evidence of an association between
allergy and IBS takes the form of two small, double blind, placebo-controlled studies of disodium cromoglycate in IBS.
Disodium cromoglycate inhibits the release of inflammatory mediators by inhibiting degranulation of mast cells (prevents the release of histamine etc) following contact with an allergen. Hence, the effect of this drug in IBS may be due to the curtailment of an allergen-mediated response. A larger study of 428 patients comparing disodium cromoglycate and elimination diet demonstrated that disodium cromoglycate was as effective as an elimination diet in improving symptoms.
Further investigation
While there is no clear evidence to suggest that IBS is an infective condition, the observation that 30% of patients develop symptoms after an episode of gastroenteritis raises a question as to possible mechanisms for the association. One possibility is that inflammation of the bowel causes increased mucosal permeability thus increasing exposure of the immune system to dietary and microbial antigens. This might allow ‘priming’ of the mucosal immune system and predispose to hypersensitivity responses. Specific serological data (derived from analysis of the blood) to support this hypothesis do not exist however. Clearly investigation into the mechanism of this association warrants further research.
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