I've been reading a lot of research articles, trying to get an idea of what's going on with my delayed food allergies.
By "delayed food allergy", I mean an allergy that doesn't show up in blood tests for IgE food allergy, and is similar to the food reactions I have.
My food reactions start about 1/2 hr after eating the food and last about 4 days. Mostly, it's a groggy sick feeling, but I've also had belly pain, back pain, frequent urination, joint pain, mild itchiness all over my body, and psychological symptoms like anxiety, tension, being more emotionally reactive. This kind of food reaction seems to be rather common, except that I've had pain in my kidney area and I haven't heard of anyone else having this symptom. I can have a reaction from a fraction of a milligram of food protein.
These reactions are acquired. I have gotten many new such allergies when I ate foods often. So they involve the immune system and are legitimately called allergies.
Here's the picture I've come up with:
The mucous membrane lining the gut has mast cells in it. The mast cells aren't right on the surface and normally various mechanisms suppress IgE food allergy.
When the gut barrier is somehow disrupted, or the regulatory T-cell aren't working right, or whatever - one can develop specific IgE antibodies to foods. See "Food Allergy" by Wang and Sampson
http://www.ncbi.nlm.nih.gov/pubmed/21364287 for more on how the body maintains tolerance to foods.
People who are allergic tend to have higher gut permeability, and are more likely to have IBS. Many people with food hypersensitivities have allergy problems such as allergic rhinitis, eczema and asthma. People with IBS and allergies tend to have higher numbers of IgE-armed mast cells in their gut, than people with IBS but no allergies. See "Indications of ‘atopic bowel’ in patients with self-reported food hypersensitivity"
http://www.ncbi.nlm.nih.gov/pubmed/20163379 Also see "Perceived food hypersensitivity: A review of 10 years of interdisciplinary research at a reference center"
http://www.ncbi.nlm.nih.gov/pubmed/21679125.
Celiac disease also causes higher gut permeability, I think much more so than being an allergic person.
So, people who are allergic, especially if they have a tendency to autoimmunity and develop celiac disease, are liable to develop IgE-mediated allergic reactions in their gut.
It's possible to have allergic reactions that are localized in a specific organ, so that skin and blood tests are negative - but one still has an allergy. See "‘Entopy’: local allergy paradigm"
http://www.ncbi.nlm.nih.gov/pubmed/20642577 "Local allergic rhinitis" is IgE-mediated nasal allergy that doesn't show up on skin or blood tests. See
http://www.jiaci.org/issues/vol20issue5/cme.pdf Local allergies are best understood for the nose, but there's also evidence that one can have local allergies in the gut. See for example "Local allergic reaction in food hypersensitive adults despite a lack of systemic food-specific IgE"
http://www.ncbi.nlm.nih.gov/pubmed/11994715 I don't know why some people would have local food allergies in their gut, and others systemic food allergies. The symptoms of systemic food allergies can be immediately life-threatening, so the body has evolved to try and prevent this. The immediate part of local food allergies may be less intense than in systemic food allergies. See "Response to intestinal provocation monitored by transabdominal ultrasound in patients with food hypersensitivity"
http://www.ncbi.nlm.nih.gov/pubmed/16028432.
The symptoms of delayed food allergies are different from systemic food allergies. I've experienced this myself. I had an "equivocal" result for corn allergy in a blood test for IgE antibodies, and when I ate some corn after doing an elimination diet, I got nasal congestion. Other foods didn't do this to me. Also, I was eating date sugar at one time (ground up dates). Dates have a lot of yeast, and I have a yeast allergy in skin tests. The date sugar caused awful hives on my legs, I was sick in bed for days, rubbing calamine lotion on the hives. The hives went away when I stopped eating date sugar. Other foods didn't cause hives, except that for awhile I had some minor itchy patches on my legs that came and went, likely caused by foods since I don't have skin allergies.
When someone has a systemic food allergy, there's some kind of control mechanism that has failed. In the case of delayed food allergies, it hasn't failed.
One of the ways that the body suppresses IgE-mediated allergic reactions is to generate IgG antibodies. IgG4 antibodies can influence allergic responses, presumably by acting as "blocking antibodies", i.e. they bind to food antigens before they can reach mast cells. An antibody bound to an antigen is called an "immune complex". See
http://medical-dictionary.thefreedictionary.com/blocking+antibody and
Food Allergy: Adverse Reaction to Foods and Food Additives by Metcalfe, Sampson, Simon and Lack, p. 550 and "IgG-blocking antibodies inhibit IgE-mediated anaphylaxis in vivo through both antigen interception and FcγRIIb cross-linking"
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1378186/When lots of immune complexes get into the bloodstream, they can cause symptoms elsewhere in the body, such as swollen, painful joints, a raised skin rash, nephritis (kidney damage, causing blood proteins and even red blood cells to leak into the urine), diminished blood flow to the brain, or gut spasms. See
http://www.britannica.com/EBchecked/topic/720823/immune-system-disorder/215507/Type-III-hypersensitivity Does some of the mental fog that people have from delayed food allergies, result from diminished blood flow to the brain?
Many people with celiac disease say they have inflammatory reactions to other foods besides gluten. It looks like what is going on is that celiac disease involves an autoimmune attack which damages the gut lining, causing increased intestinal permeability and other changes in the gut lining. This results in IgE-mediated reactions to food - but since most celiacs don't have the particular defect that results in systemic food allergies, they develop delayed food allergies instead. The body tries to prevent these symptoms, resulting in large numbers of IgG immune complexes, which get into the bloodstream and cause problems like joint pain and perhaps mental fog.
Celiac disease, like being an allergic person, may result in increased mast cells in the gut. Dr. Scot Lewey, a gastroenterologist who's a celiac disease specialist in Colorado (see
http://thefooddoc.blogspot.com/ tests for "mastocytic enterocolitis" in some of his patients with celiac disease. The testing involves a biopsy of the small intestine with a special stain for mast cells, and the pathologist looks for excessive mast cells. See "Mastocytic enterocolitis: increased mucosal mast cells in chronic intractable diarrhea"
http://www.ncbi.nlm.nih.gov/pubmed/16519565 and "Allergic Mastocytic Gastroenteritis and Colitis: An Unexplained Etiology in Chronic Abdominal Pain and Gastrointestinal Dysmotility"
http://www.hindawi.com/journals/grp/2012/950582/ I don't know that mastocytic enterocolitis has been definitely associated with the "other food intolerances" in celiac disease. Dr. Lewey treats it with oral cromolyn, H1 and H2 antihistamines, Singulair and probiotics.
I've found that taking oral cromolyn, Singulair and loratadine at least an hour before tiny amounts of foods I'm allergic to, reduces my food reactions greatly. I'm taking 20 mg loratadine (Claritin), which seems to be more effective than the usual 10 mg dose. From what I've seen online, one can take 20 mg loratadine if the side effects aren't too unpleasant. The brand name for oral cromolyn is Gastrocrom, but Gastrocrom is horribly expensive. I get it much more cheaply in powder form from a compounding pharmacy, and I dissolve the powder in hot water and drink.
That cromolyn and antihistamines help, suggests that my food reactions do start with mast cells. In the first couple years after I went gluten-free, my food reactions were much worse, and they might have also involved immune complexes.
A non-IgE mechanism for antigen-specific triggering of mast cells has been found - immunoglobulin free light chains (FLC's). An immunoglobulin molecule (such as IgE) is composed of two light chains and two heavy chains, but immunoglobulin light chains also wander around by themselves. See
http://dspace.library.uu.nl/handle/1874/221010 FLC's are produced in some autoimmune diseases, and they may cause as much sensitivity to antigen as in IgE-mediated allergic reactions.
So perhaps delayed food allergies are mediated by FLC's rather than by IgE. FLC's may also be involved in inhalant allergies, see "Evidence for the involvement of free light chain immunoglobulins in allergic and nonallergic rhinitis"
http://www.ncbi.nlm.nih.gov/pubmed/19818484Both "non-IgE" (unknown mechanism actually) and IgE-mediated food allergies involve Th2 skewing of the immune system. See "Food Allergy" by Wang and Sampson
http://www.ncbi.nlm.nih.gov/pubmed/21364287 and "Antigen-specific T-cell responses in patients with non–IgE-mediated gastrointestinal food allergy are predominantly skewed to TH2"
http://www.ncbi.nlm.nih.gov/pubmed/23083674 Th2 is antibody-mediated immunity. So it seems like these allergies aren't cell-mediated. Also, cell-mediated allergic reactions are known to require a time period longer than 24 hours - see "Usefulness of Lymphocyte Stimulation Test for the Diagnosis of Intestinal Cow’s Milk Allergy in Infants"
http://www.ncbi.nlm.nih.gov/pubmed/21912174, and delayed food allergies often start making people feel sick within a few hours of eating the food.
It's common for people with delayed food allergies, including celiacs with "other food intolerances", to become hypersensitive once they start avoiding the food. The felt reaction that celiacs have when they accidentally get "glutened" is similar to the symptoms from "other food intolerances" - so it seems likely that celiacs develop a delayed food allergy to gluten grains, which is separate from the autoimmune process triggered by the gliadin protein in gluten. Wheat is a major allergen, after all.
For me, delayed food allergies, both to gluten and non-gluten foods, had HUGE psychological effects. With any of the foods I have these delayed allergies to, I tend to get irritable and more emotionally reactive. Little things loom large. Taking allergy medications beforehand helps prevent this.
Histamine is a neurotransmitter, see
http://www.ncbi.nlm.nih.gov/pubmed/21713693. Perhaps histamine acting as a neurotransmitter in the gut, explains the psychological aspects of delayed food allergies.