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Eleftheriou, P. Disease-Correlated Antibodies against Food-Derived Antigens. Encyclopedia. Available online: https://encyclopedia.pub/entry/58932 (accessed on 21 December 2025).
Eleftheriou P. Disease-Correlated Antibodies against Food-Derived Antigens. Encyclopedia. Available at: https://encyclopedia.pub/entry/58932. Accessed December 21, 2025.
Eleftheriou, Phaedra. "Disease-Correlated Antibodies against Food-Derived Antigens" Encyclopedia, https://encyclopedia.pub/entry/58932 (accessed December 21, 2025).
Eleftheriou, P. (2025, September 07). Disease-Correlated Antibodies against Food-Derived Antigens. In Encyclopedia. https://encyclopedia.pub/entry/58932
Eleftheriou, Phaedra. "Disease-Correlated Antibodies against Food-Derived Antigens." Encyclopedia. Web. 07 September, 2025.
Disease-Correlated Antibodies against Food-Derived Antigens
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This entry is adapted from: https://doi.org/10.3390/biom15081085

A brief review on the Diseases related to increased Antibodies against Food-Derived antigens. (Derived from the article "Increased Concentration of Anti-Egg Albumin Antibodies in Cerebrospinal Fluid and Serum of Patients with Alzheimer’s Disease—Discussion on Human Serpins’ Similarity and Probable Involvement in the Disease Mechanism" ).

antibodies food antigens anti-egg albumin anti-casein anti-gliadin anti-Neu5Gc Alzheimer's Disease Schizophrenia depression auto-immune diseases

Numerous studies have suggested the involvement of antibodies against food derived antigens in the development and progression of several diseases among which, bowel [1][2], auto-immune [3] and degenerative diseases [4]. Migraine [5], other neurological diseases [6][7][8], and mental disorders [9][10][11] have also been corelated with food-derived antigens.

Normally, IgA and IgM antibodies against food antigens may be detected in healthy people because of oral tolerance, a process related to the mucosal immune system’s ability to differentiate between pathogenic and non-pathogenic antigens, mostly described as immunological ignorance. However, dysregulation of this process may lead to increased concentrations of IgG as well as IgM food antigen-specific antibodies in the serum of certain individuals [12][13]. Cross-reaction of these antibodies with human proteins or peptides with increased sequence/structural identity or similarity with the food antigens (molecular mimicry) may be involved in the development or progression of the related diseases [6][14][15].

In general, when conditions like leaky intestine exist, food antigens can cause disorders through at least three different ways, all based on similarity of the molecule with human proteins: a) Production of antibodies which may cross-react with the human proteins usually diminishing the concentration of these proteins, disrupting the mechanism served by them and triggering inflammatory responses [16], b) Direct involvement in a mechanism, since molecular mimicry may enable appropriate interactions [17] and c) Interaction with the target molecule of the homologue protein in an unsuccessful manner preventing the successful interaction of the homologue protein.

Although humans consume a great variety of foods with thousands of proteins and other ingredients, a small number of foods and dietary components have been correlated with diseases. Among the most common food ingredients which are related to diseases (Figure 1) is gliadin, a component of gluten proteins of wheat products, mostly related to intestinal disorders [1][2]. Gluten implication in other diseases such as multiple sclerosis (MS) [7][8], autism [18] and schizophrenia [19] has also been mentioned. However, it is not clear if there is a straight correlation, or the effect concerns the leaking of other factors to the serum, because of the increased intestinal permeability caused by the reaction to gluten. Casein, the main milk protein, has also been related to MS, depression, and bipolar disorder, connecting neurological and mental disorders with dairy food consumption [8][10][12]. Mixed antibodies against egg and bovine antigens have displayed specificity toward human antigens, among which proteins related to Alzheimer’s Disease [12]. Investigating cross-reaction of antibodies to specific food antigens with various purified human tissue antigens indicated a positive reaction between antibodies against egg, milk, wheat and corn with myelin basic protein (MBP) or Aβ42 peptide, both related to amyloid plaque formation [12]. Neu5Gc, a sialic acid present in animals but not in humans, represents another kind of molecules related to immunologic response. It can be incorporated into human glycoproteins triggering immunologic response in some individuals and has been correlated with autoimmune diseases, such as Hashimoto’s Thyroiditis and cancer [3][20].

   Figure 1. The most common food incedients related to diseases

Specific dietary recommendations, based on the food-antigen specific antibodies relieved the symptoms of the diseases in some cases [8][21][22][23][24][25][26]. However, antibodies against specific food antigens are usually present only in a subgroup of patients in all related diseases, suggesting that such immune responses represent one of multiple contributing factors in disease onset or progression.

In the recent study of Amanatidou D., Eleftheriou P. et al [27], antibodies against egg-albumin, bovine-casein and N-Glycolyl-Neuraminic acid (Neu5Gc) were measured in the cerebrospinal fluid (CSF) and serum of the patients (Figure 2A) using enzyme-linked immunosorbent assay (ELISA). Zero anti-Neu5Gc and low concentration of anti-casein antibodies were detected. However, increased anti-native egg-albumin antibodies were present in the serum of patients of all stages with 65% positivity (p<0.001) in mild disease and a higher percentage in females (81.9%, p<0.001). Lower serum positivity to anti-denatured egg albumin antibodies was observed showing gradual increase with severity and higher prevalence also in females. In the CSF, anti-native and anti-denatured egg-albumin antibodies were mainly observed in severely ill patients with accumulative positivity to either antigen reaching 61.8% in severe vs 15% in mild disease (p<0.001). Increased values were mainly observed in males (Figure 2B) [27].

Figure 2. A. Increase in anti-Neu5Gc, anti-native casein and anti-native egg-albumin antibody concentration in the CSF of AD patients with mild, intermediate and severe disease compared to healthy individuals (%). B. Percentage of CSF samples % of anti-native egg albumin positive, anti-denatured egg albumin positive and mixed positive samples in AD patients with mild and severe disease. C. Structural alignment of egg-albumin (PDB ID: 1OVA) with Serpin A3 (PDB: 1QMN). D. Structure of serpin A1 (a1-antitrypsin) which presents 30%sequence identity with egg-albumin. The identical amino-acids are shown in yellow [27].

As already mentioned, increased concentrations of antibodies against food-derived antigens like egg-albumin presuppose an intestinal or immunologic disturbance such as leaky intestine. However, increased Blood Brain Barrier (BBB) permeability may contribute to the high antibody concentration in Cerebrospinal Fluid. Both intestinal and BBB disturbances are common in AD patients [12]. Immune system impairment may also characterize some of the patients as it is common characteristic of aging [28]. In Alzheimer’s Disease, bacterial dysbiosis, the main cause of impaired intestinal permeability [29] is also a common and gradually progressive characteristic, affecting both colon and small intestine [30][31] with colon dysfunction detected in the first stages of the disease [32]. Dysbiosis is probably involved in oxidative and inflammatory conditions in AD patients [33] and may be implicated in protein modification and disregulation of  digestion process. The sex differences, known to exist in intestinal microbiota [34][35], oxidative conditions [36][37][38] and intestinal permeability as well as the increased male susceptibility in BBB disfunction [39] may contribute to the sex differences observed anti-egg albumin antibodies in the serum and CSF. Although events of the disease may justify the observed results, experimental work is needed to further evaluate the probable correlation.

Anti-egg-albumin antibodies may be implicated in Disease mechanism through sequence/structural similarity with human proteins, mainly serpins (Figure 2C,D) and it would be worth of consideration in further investigations and therapeutic strategies. BLAST research revealed 21-42% similarity of ovalbumin with 35 human serine protease inhibitors (serpins) and with three non-serpin proteins: the Serpin-like minor histocompatibility protein HMSD, the phosphatidylinositol 5-phosphate 4-kinase type-2 gamma (PIP4K2C) and the N-acylglucosamine 2-epimerase (RENBP) [27]. Many of these molecules are related to the nervus system physiology or AD linked mechanisms and relevant disorders. Of great interest is the sequence/structural similarity with human serpins, involved in processes which exhibit impairment in AD such as intestinal permeability and inflammation (serpins A1, A2), Blood Brain Barrier (serpin A8, known as angiotensin, AGT, and its active metabolite, angiotensin II, AngII), and Central Nervus System (CNS) function (serpins A1, A3, A8, B1, E1, F1, I1) [27].

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