Major depressive disorder (MDD) is the most common nonfatal disease burden worldwide. Systemic chronic low-grade inflammation has been reported to be associated with MDD progression by affecting monoaminergic and glutamatergic neurotransmission. However, whether various proinflammatory cytokines are abnormally elevated before the first episode of depression is still largely unclear. Here, we evaluated 184 adolescent patients who were experiencing their first episode of depressive disorder, and the same number of healthy individuals was included as controls. We tested the serum levels of high-sensitivity C-reactive protein (hs-CRP), tumor necrosis factor-α (TNF-α), IgE, 14 different types of food antigen-specific IgG, histamine, homocysteine, S100 calcium-binding protein B, and diamine oxidase. We were not able to find any significant differences in the serum levels of hs-CRP or TNF-α between the two groups. However, the histamine level of the patients (12.35 μM) was significantly higher than that of the controls (9.73 μM, P < 0.001, Mann-Whitney U test). Moreover, significantly higher serum food antigen-specific IgG positive rates were also found in the patient group. Furthermore, over 80% of patients exhibited prolonged food intolerance with elevated levels of serum histamine, leading to hyperpermeability of the blood-brain barrier, which has previously been implicated in the pathogenesis of MDD. Hence, prolonged high levels of serum histamine could be a risk factor for depressive disorders, and antihistamine release might represent a novel therapeutic strategy for depression treatment.
Adolescent ; Biomarkers ; blood ; C-Reactive Protein ; Chronic Disease ; Cytokines ; Depressive Disorder, Major ; blood ; epidemiology ; etiology ; Female ; Food Hypersensitivity ; blood ; complications ; Histamine ; blood ; Homocysteine ; blood ; Humans ; Immunoglobulin E ; blood ; Immunoglobulin G ; blood ; immunology ; Inflammation Mediators ; blood ; Male ; Risk Factors ; S100 Calcium Binding Protein beta Subunit ; blood ; Young Adult

OBJECTIVETo investigate the effects of adipose-derived stem cells (ADSC) and non-methylated CpG-oligodeoxynucleotides (CpG-ODN) on the expression of peripheral blood CD4CD25regulatory T (Treg) cells in young mice with food allergy, as well as their immune intervention effects.

METHODSA total of 40 female BALB/c mice were randomly divided into control group, allergic group, ADSC treatment group, and CpG-ODN treatment group, with 10 mice in each group. A mouse model of food allergy was established by intraperitoneal injection and intragastric administration of ovalbumin (OVA) for sensitization and challenge. The mice in the control group were treated with normal saline at the same dose; the mice in the ADSC treatment group were given intraperitoneal injection of ADSC (1×10cells for each mouse) before and after OVA challenge, and those in the CpG-ODN treatment group were given intraperitoneal injection of non-methylated CpG-ODN solution (40 μg for each mouse) at 1 hour before challenge by gavage. The allergic symptom scores were determined for each group after model establishment. ELISA was used to measure the serum level of OVA-IgE. Flow cytometry was used to measure the percentage of peripheral blood CD4CD25Treg cells. Hematoxylin and eosin staining was used for the pathological analysis of the jejunum.

RESULTSThe allergic group had significantly higher allergic symptom scores and serum level of OVA-IgE than the control group (P<0.05). There were no significant differences in the allergic symptom score and the serum level of OVA-IgE between the ADSC treatment group and the CpG-ODN treatment group (P>0.05), but these two groups had significantly lower allergic symptom scores and serum level of OVA-IgE than the allergic group and significantly higher allergic symptom scores and serum level of OVA-IgE than the control group (P<0.01). The allergic group had a significantly lower percentage of peripheral blood CD4CD25Treg cells than the control group (P<0.05). The ADSC treatment group and the CpG-ODN treatment group had a significantly higher percentage of peripheral blood CD4CD25Treg cells than the allergic group (P<0.05); there were no significant differences between these two groups or between them and the control group (P>0.05). Pathological results showed structural damage and edema in the jejunal villi, a large number of eosinophils, and lymphocyte infiltration in the allergic group, while the ADSC treatment group and the CpG-ODN treatment group had less structural damage and edema in the jejunal villi, a lower number of eosinophils, and less lymphocyte infiltration.

CONCLUSIONSADSC and non-methylated CpG-ODN have a certain effect in the treatment of food allergy and can increase the percentage of peripheral blood CD4CD25Treg cells and reduce the level of OVA-IgE. They may be associated with the induction of immune tolerance and these two treatment have comparable effects. Detailed mechanisms of action still need further investigation.

Adipose Tissue ; cytology ; Adjuvants, Immunologic ; pharmacology ; Animals ; Female ; Food Hypersensitivity ; immunology ; therapy ; Immunoglobulin E ; blood ; Mice ; Mice, Inbred BALB C ; Oligodeoxyribonucleotides ; pharmacology ; Ovalbumin ; immunology ; Stem Cell Transplantation ; T-Lymphocytes, Regulatory ; drug effects ; immunology

OBJECTIVETo establish a food allergy model in Brown Norway (BN) rats by gavage of ovalbumin (OVA) without any adjuvant, and to evaluate this model.

METHODSA total of 20 male BN rats aged 3 weeks were randomly divided into allergy group and control group (n=10 each). BN rats in the allergy group were given OVA 1 mg per day by gavage, and all the rats were treated for 41 days continuously. On day 42, the rats in the allergy group were given OVA 100 mg by gavage for challenge. The rats in the control group were given normal saline of the same volume by gavage. Differences in body length, body weight, and food intake were compared between the two groups on days 7, 14, 21, 28, 35, and 42. ELISA was used to measure the serum OVA-IgE level and plasma histamine level after challenge on day 42, and the changes in rats' appearance and fecal properties were observed. The model of food allergy was considered successful when the serum OVA-IgE level in the allergy group was no less than the mean serum OVA-IgE level + 3 standard deviation in the control group.

RESULTSThere were no significant differences in body length, body weight or food intake between the allergy and control groups at all time points (P>0.05). On day 21, the control group had a significantly higher food intake than the allergy group (P<0.05). On day 42 after challenge, the allergy group showed significantly higher serum OVA-IgE and plasma histamine levels than the control group (P<0.05). The sensitization rate (rate of successful modeling) was 90%. The fecal properties showed no significant differences between the two groups.

CONCLUSIONSOVA by gavage without any adjuvant can successfully establish the model of food allergy in BN rats and has a high success rate. Food allergy induced by OVA may reduce food intake within a short period of time, but no influence on rats' body length or body weight has been observed.

Animals ; Disease Models, Animal ; Food Hypersensitivity ; etiology ; immunology ; Histamine ; blood ; Immunoglobulin E ; blood ; Male ; Ovalbumin ; immunology ; Rats ; Rats, Inbred BN

OBJECTIVETo investigate the immunoregulatory effect of adipose-derived stem cell (ADSC) transplantation by intraperitoneal injection in food-allergic young mice before and after ovalbumin (OVA) sensitization.

METHODSThirty-two 3-week-old female Balb/c mice were randomly divided into control, allergic model, ADSC treatment, and ADSC prevention groups (n=8 each). A young mouse model of food allergy was established by OVA sensitization via intraperitoneal injection. Each mouse from the prevention and treatment groups was transplanted with 1×10(6) ADSCs on days 1 and 15 post-sensitization, respectively. The allergic symptoms of all groups were observed and scored. The jejunal villi and inflammatory cell infiltration were observed by hematoxylin-eosin staining. Serum levels of allergy-related inflammatory cytokines were measured by Luminex.

RESULTSCompared with the allergic model group, the ADSC prevention and ADSC treatment groups had significantly reduced allergic symptom scores (P<0.05). The two groups also showed significantly alleviated allergic pathological damage of the jejunal mucosa. Serum levels of interleukin (IL)-4, IL-5, IL-6, IL-17A, IL-22 and IL-23 were significantly lower in the ADSC prevention and treatment groups than in the allergic model group (P<0.05). However, the ADSC treatment group had a significantly increased serum interferon-γ level and a significantly reduced serum monocyte chemotactic protein-1 level compared with the allergic model and ADSC prevention groups (P<0.05).

CONCLUSIONSADSC transplantation, performed before or after sensitization, has an immunoregulatory effect on food allergy in young Balb/c mice, but this effect is better if transplantation is performed after sensitization.

Adipose Tissue ; cytology ; Animals ; Cytokines ; blood ; Disease Models, Animal ; Female ; Food Hypersensitivity ; immunology ; therapy ; Male ; Mice ; Mice, Inbred BALB C ; Stem Cell Transplantation

OBJECTIVETo explore the effect of non-methylated cytosine-phosphate-guanine oligodeoxynucleotides (CpG-ODN) on serum transforming growth factor (TGF)-β and immune regulation in ovalbumin (OVA)-sensitized young mice.

METHODSThirty female BALB/c mice (2-3 weeks old) were randomly divided into control, model, and CpG-ODN intervention groups. A young mouse model of food allergy was established by OVA sensitization. Normal saline of the same volume was used for replacement in the control group. The mice in the intervention group were intraperitoneally injected with CpG-ODN solution 1 hour before every OVA sensitization. Allergic symptoms were observed and scored for each group. The jejunal tissue was histopathologically examined with hematoxylin-eosin staining. Serum OVA-IgE level was measured using ELISA. Serum concentrations of interleukin (IL)-4, interferon (IFN)-γ, and TGF-β were determined by CBA.

RESULTSAllergic symptoms were observed in the model group and the jejunal tissue showed the pathological characteristics of type I allergic reaction. The allergic symptom scores in the model and CpG-ODN intervention groups were significantly higher than in the control group (P<0.01). The serum levels of OVA-IgE, IL-4, and TGF-β were significantly higher in the model group than in the control and CpG-ODN intervention groups (P<0.05). The CpG-ODN intervention group had significantly higher serum levels of OVA-IgE, IL-4, and TGF-β than the control group (P<0.05). Compared with the control and CpG-ODN intervention groups, the model group had a significantly reduced IFN-γ level (P<0.05).

CONCLUSIONSThe serum TGF-β level is increased in the young mouse model of OVA-sensitized food allergy and is involved in the allergy mechanism. Non-methylated CpG-ODN can reduce the serum TGF-β level in sensitized young mice and play an immunoregulatory role in food allergy.

Aging ; Animals ; DNA Methylation ; Female ; Food Hypersensitivity ; drug therapy ; immunology ; Immunoglobulin E ; blood ; Interleukin-4 ; blood ; Mice ; Mice, Inbred BALB C ; Oligodeoxyribonucleotides ; pharmacology ; Ovalbumin ; immunology ; Transforming Growth Factor beta ; blood

OBJECTIVETo explore the relationship between the major allergens of 6 common allergic foods and IgA nephropathy.

METHODSA sensitive sandwich enzyme-linked immunosorbent assay (ELISA) was used to detect the serum levels of food-specific IgA1, IgG and IgE in 31 patients with IgA nephropathy and 80 healthy volunteers. All the patients were examined for a history of food allergy using a questionnaire.

RESULTSSerum levels of IgA1 and IgG against the major allergens of the 6 common allergic foods were significantly higher in patients with IgA nephropathy than in healthy volunteers (P<0.05). There was no detectable food-specific IgE antibodies in the two groups. No patients had a clear history of food allergy. All the patients with increased IgG levels specific to 4 or more foods simultaneously had proteinuria.

CONCLUSIONSSome foods especially the highly allergic ones may participate in the pathogenesis and progression of IgA nephropathy.

Adult ; Antibody Specificity ; Case-Control Studies ; Female ; Food Hypersensitivity ; classification ; immunology ; Glomerulonephritis, IGA ; blood ; immunology ; Humans ; Immunoglobulin A ; blood ; Immunoglobulin E ; blood ; Immunoglobulin G ; blood ; Male ; Young Adult

Food allergy is defined as reaction to a food which has an immunologic mechanism. Its prevalence is increasing in children globally and is therefore of increasing clinical importance. A useful clinical approach is to distinguish food allergic reactions by the timing of clinical reaction in relation to food exposure and classified as immediate (generally IgE-mediated) and delayed (generally non-IgE-mediated), with the exception of eczema and eosinophilic gastrointestinal disease, which, when associated with food allergy may be associated with either mechanism. This review is aimed at providing the clinician with a Singaporean perspective on the clinical approach and management of these disorders.
Breast Feeding ; Child ; Child, Preschool ; Eczema ; diagnosis ; immunology ; Food Hypersensitivity ; diagnosis ; prevention & control ; Humans ; Hypersensitivity, Delayed ; diagnosis ; prevention & control ; Immunoglobulin E ; blood ; Infant ; Infant, Newborn ; Skin Test End-Point Titration

Anisakidae larvae can cause anisakiasis when ingested by humans. Although several groups have reported a gastrointestinal Anisakis allergy among people in Spain and Japan, our report is the first to summarize the clinical features of 10 Anisakis allergy cases in Korea. We enrolled 10 Korean patients (6 men and 4 women) who complained of aggravated allergic symptoms after ingesting raw fish or seafood. Sensitization to Anisakis was confirmed by detecting serum specific IgE to Anisakis simplex. The most common manifestation of anisakiasis was urticaria (100%), followed by abdominal pain (30%) and anaphylaxis (30%). All patients presenting with these symptoms also exhibited high serum specific IgE (0.45 to 100 kU/L) to A. simplex. Nine patients (90%) exhibited atopy and increased total serum IgE levels. The fish species suspected of carrying the Anisakis parasite were flatfish (40%), congers (40%), squid (30%), whelk (10%), and tuna (10%). Anisakis simplex should be considered as a possible causative food allergen in adult patients presenting with urticaria, angioedema, and anaphylaxis following the consumption of raw fish or seafood.
Abdominal Pain/immunology ; Adult ; Aged ; Anaphylaxis/immunology ; Angioedema/immunology ; Animals ; Anisakiasis/complications/ethnology/*immunology ; Anisakis/*immunology ; Antibodies, Helminth/*blood ; Asian Continental Ancestry Group ; Female ; Food Hypersensitivity/complications/ethnology/*immunology ; Humans ; Immunoglobulin E/*blood ; Korea/epidemiology ; Male ; Middle Aged ; Seafood/*adverse effects/parasitology ; Urticaria/immunology ; Young Adult

OBJECTIVEThe causes of chronic diarrhea in children are complex. At present, food allergy is generally viewed as an important cause of this disorder, and IgG-mediated delayed allergy plays a major role in this process. This study aimed to explore the link between food specific IgG and chronic diarrhea in children, as well as the value of food allergens-specific IgG antibody detection in the management of this disorder.

METHODSEighty-two children with chronic diarrhea and 30 healthy controls were enrolled. Serum levels of specific IgG antibody to 14 kinds of food were detected using ELISA. The results were classified into four grades: Grade 0 (negative), Grade 1 (mild allergy), Grade 2 (moderate allergy) and Grade 3 (severe allergy). The patients received a diet treatment based on the results of food specific IgG antibody detection. Children with negative IgG antibody were allowed to continue their current diet. In children with Grade 1 allergy, the food responsible for the IgG antibody positive test was given only at an interval of four days. In children with Grade 2 or 3, the offending food was eliminated from the diet.

RESULTSOf the 82 children with chronic diarrhea, 79 (96.2%) had increased specific IgG levels for one or more of the 14 foods tested compared to 8 (26.7%) of the controls (P <0.01). The majority of patients showed increased specific IgG levels for milk (68.3%) and egg (62.2%). A low proportion of patients (2.4%) was allergic to chicken, and no patient was allergic to pork. The symptoms were improved in 65 patients (79.3%) after 1 week to 3 months of diet treatment.

CONCLUSIONSFood allergy is one of major causes of chronic childhood diarrhea. Food specific IgG antibody detection may assist in the dietary management of this disorder.

Allergens ; immunology ; Child ; Child, Preschool ; Chronic Disease ; Diarrhea ; etiology ; immunology ; Female ; Food Hypersensitivity ; immunology ; Humans ; Immunoglobulin G ; blood ; Infant ; Male

Genetically modified (GM) soybean (carrying the EPSPS transgene) is the most common GM food in Korea. In order to assess whether genetic modification increases the allergenic risk of soybeans, the allergenicity and IgE-reactive components of wild-type and GM soybean extracts were compared in allergic adults who had been sensitized to soybeans. We enrolled 1,716 adult allergy patients and 40 healthy, non-atopic controls. Skin prick tests and IgE enzyme linked immunosorbent assays (ELISAs) were performed using wild-type and GM soybean extracts, along with other common inhaled allergens. The specificities of serum IgE antibodies from allergic patients and the identities of the IgE-reactive components of the soybean extracts were compared using ELISA inhibition testing, 2-dimensional gel electrophoresis, and IgE immunoblotting. To evaluate the effects of digestive enzymes and heat treatment, the soybean extracts were heated or pre- incubated with or without simulated gastric and intestinal fluids. The IgE sensitization rates to wild-type and GM soybeans were identical (3.8% of allergic adults), and circulating IgE antibodies specific for the two extracts were comparable. The results of the ELISA inhibition test, SDS-PAGE, and IgE immunoblotting showed a similar composition of IgE-binding components within the wild-type and GM extracts, which was confirmed using two-dimensional gel electrophoresis, IgE immunoblotting, and amino acid sequencing. None of the subjects had a positive response to purified EPSPS protein in the skin prick test, ELISA, or IgE immunoblot analysis. These findings suggest that the IgE sensitization rate to GM soybean extracts is identical to that of wild-type soybean extracts in adult allergy patients. In addition, based on both in vivo and in vitro methods, the allergenicity of wild type and GM soybean extracts was identical.
Soybeans/*immunology ; Skin Tests ; Protein Structure, Tertiary ; *Plants, Genetically Modified ; Middle Aged ; Immunoglobulin E/blood/chemistry ; Immunoblotting ; Humans ; Food Hypersensitivity/etiology/*immunology ; Food/*adverse effects ; Enzyme-Linked Immunosorbent Assay ; Electrophoresis, Gel, Two-Dimensional ; *Crops, Agricultural ; Allergens/*immunology ; Adult ; Adolescent