PURPOSE: Specific oral immunotherapy (SOIT) using interferon-gamma (IFN-gamma) has been successful as a food allergy treatment. Interleukin-10 (IL-10)-producing regulatory B cells (Br1s) play a role in immune tolerance to food allergens. In addition, IFN-gamma shows tolerogenic effects on allergen-induced Br1 responses. METHODS: Eleven patients that were allergic to cow's milk and 12 milk-tolerant subjects were selected by double-blind placebo-controlled food challenge (DBPCFC) and clinical characteristics. The immunomodulatory effects of IFN-gamma on allergen-specific Br1 responses were evaluated in 6 milk allergy patients and 8 milk-tolerant subjects. Peripheral blood mononuclear cells (PBMCs) from subjects were stimulated with casein and/or IFN-gamma and analyzed by flow cytometry. RESULTS: IFN-gamma had no effect on total cell counts or the proportion of Br1 cells in PBMCs. IFN-gamma stimulation did not change total Br1 cell counts or the percentage of Br1s among CD5(+) B cells in the milk allergy or the milk-tolerant groups. In the milk allergy group, Br1 counts were not different between the control and the casein stimulation but significantly increased in the IFN-gamma + casein stimulated cells, and the Br1 fractions were decreased after casein stimulation and recovered in the addition of IFN-gamma for stimulation. In the milk-tolerant group, Br1 counts increased in the casein stimulated cells and in the IFN-gamma + casein stimulated cells, but the increase was significantly less when IFN-gamma was added, and the Br1 fractions were increased after casein stimulation and IFN-gamma + casein stimulation, that was not significant when IFN-gamma was added. CONCLUSIONS: IFN-gamma-induced allergen-specific Br1 responses in the PBMCs of milk allergy patients play a role in milk allergen-specific tolerance induction in vitro. Further investigations into the molecular immunological mechanisms underlying the induction of allergen-specific Br1 responses are needed.
Allergens ; B-Lymphocytes ; B-Lymphocytes, Regulatory ; Caseins ; Cell Count ; Dermatitis, Atopic ; Food Hypersensitivity ; Humans ; Immune Tolerance ; Immunotherapy ; Interferon-gamma ; Interleukin-10 ; Milk ; Milk Hypersensitivity

Many trials have been done on steroid-resistant atopic dermatitis. Recently, intravenous immune globulin (i.v.IG) was reported to be effective in the treatment of steroid-dependent atopic dermatitis. The aim of this study was to clarify whether i.v.IG therapy is effective in steroid-resistant atopic dermatitis. Forty-one steroid-resistant atopic dermatitis patients were tested in this study. Patients who weighed less than 30 kg were administered 500 mg/kg of i.v.IG. Patients who weighed 30 kg or more were administered 15 g of i.v.IG. Patient evaluations and laboratory tests with peripheral bloods such as eosinophil percentages and serum IgE levels were performed at days 0, 1, 7, and 21. In the present study, patients who responded to i.v.IG therapy were classified as Group A. Twelve patients who showed transient effects with lower clinical significance were classified as Group B (29.3%). Remaining 12 patients (29.3%) in Group C showed no improvement at all. Serum IgE levels and blo eosinophil percentages were markedly decreased in Group A. I.v.IG therapy may be recommended in the treatment of atopic dermatitis with extremely high serum IgE levels.
Adolescence ; Adrenal Cortex Hormones/pharmacology* ; Child ; Dermatitis, Atopic/therapy* ; Dermatitis, Atopic/immunology ; Drug Resistance ; Eosinophils/cytology ; Female ; Human ; IgE/blood ; Immunoglobulins, Intravenous/therapeutic use* ; Immunotherapy ; Male

B cells are generally considered to positively regulate immune responses by producing antigen-specific antibodies. B cells are classified into classical CD5- conventional B cells and CD5+ B1 cells. The latter produce multi-specific autoantibodies and are thought to be involved in autoimmune diseases. However, evidence supporting a B cell negative regulatory function has accumulated over the past 30 years. Multiple reports have suggested that absence, or loss, of regulatory B cells exacerbates symptoms of both allergic (including contact hypersensitivity and anaphylaxis) and autoimmune (such as experimental autoimmune encephalomyelitis, chronic colitis, and collagen-induced arthritis) diseases, and in lupus-like models of autoimmunity. Regulatory B cells are characterized by production of the negative regulatory cytokines, IL-10 and TGF-beta. IL-10-producing B cells were the first regulatory B cells to be recognized and were termed 'B10' cells. IL-10-producing regulatory B cells are of the CD19(+)CD5(+)IgM(hi)IgD(lo)CD1d(hi) type. Recently, a TGF-beta-producing regulatory B cell subset, Br3, has been shown to be related to immune tolerance in food allergies. Moreover, forkhead box P3 (Foxp3)-expressing B cells have also been identified in humans and may act as regulatory B cells (Bregs). The functional image of regulatory B cells is similar to that of regulatory T cells. Because of the proliferative and apoptotic responses of Br1 and Br3 cells in immune tolerance in non-IgE-mediated food allergy, reciprocal roles and counter-regulatory mechanisms of Br1 and Br3 responses are also suspected. Additionally, different roles for regulatory B and T cells at different time points during initiation and progression of autoimmune disease are described.
Antibodies ; Asthma ; Autoantibodies ; Autoimmune Diseases ; Autoimmunity ; B-Lymphocytes ; B-Lymphocytes, Regulatory ; Colitis ; Cytokines ; Dermatitis, Atopic ; Dermatitis, Contact ; Encephalomyelitis, Autoimmune, Experimental ; Food Hypersensitivity ; Humans ; Hypersensitivity ; Immune Tolerance ; Interleukin-10 ; T-Lymphocytes ; T-Lymphocytes, Regulatory ; Transforming Growth Factor beta

The avoidance of incriminated foods is one of the principal therapies for atopic dermatitis (AD). Recently, interferon (IFN)-gamma therapy has been tried in AD with limited success. The necessity of diet therapy for the success of IFN-gamma therapy in AD was evaluated. A total of 524 AD patients participated in this study and 316 patients among them were entered into open food challenge tests. As the first step, an elimination diet was administered to 43 AD patients and 30 AD patients were enrolled as an untreated control group. As the second step, 45 AD patients were treated by both IFN-gamma therapy and elimination diet alone, 30 AD patients by elimination diet alone, 50 AD patients by IFN-gamma therapy, and 43 AD patients as controls. Clinical severity reduced significantly by using only the elimination diet in 58.1% patients with varying degrees of AD. Elimination diet improved the clinical results of IFN-gamma therapy in AD. In regard to the food challenge test, 77.8% of AD patients showed an adverse reaction to at least one food. Diet therapy itself had therapeutic effects on AD and an elimination diet might be essential for the success of IFN-gamma therapy in AD.
Adolescence ; Adult ; Child ; Child, Preschool ; Dermatitis, Atopic/drug therapy* ; Dermatitis, Atopic/diet therapy* ; Female ; Food Hypersensitivity/diet therapy ; Human ; Interferon Type II/therapeutic use* ; Male ; Treatment Outcome

PURPOSE: Atopic dermatitis is characterized by immunologic abnormalities including evidence for reduced IFN-gamma production with increased IL-4 production. Previous open trials have suggested efficacy for recombinant IFN-gamma in treatment of severe atopic dermatitis. Here we report the results of treatment with IFN-gamma in 5 patients with moderate to severe atopic dermatitis. METHODS: Atopic dermatitis was diagnosed according to typical clinical symptoms. Patients were treated with IFN-gamma for 6 weeks. Patients received 2x106 units/m2 IFN-gamma by subcutaneous injection. Serum IgE levels, total eosinophil counts with hemoglobin(Hb) concentrations, hematocrit(Hct)s, white blood cell counts(WBC), lymphocyte fractions, eosinophil fractions and platelet counts were examined before treatment and 1 week and 6 week after treatment. RESULTS: The skin lesions of all patients begun to be improved after 3 times of injection. As estimated by patients, responses showed significant improvement. Three of five patients were resolved completely who showed complete clearance of skin manifestation. and remained two patients show dramatic improvement with mild some skin lesions. WBC counts, Hemoglobins, Hematocrits, lymphocyte fractions, eosinophil fractions and platelet counts was not significantly changed before and after IFN-gamma treatment. Serum IgE levels were not markedly elevated and not reduced after IFN-gamma treatment. But total eosinophil counts were decreased 1 week after treatment and reduced to normal range 6 weeks after treatment. CONCLUSIONS: Five severe atopic dermatitis patients who did not respond to previous treatment, who had showed complication to local steroid treatment and who had severe skin lesions were treated with IFN-gamma. They showed marked improvement in skin lesions after IFN-gamma treatment and three of them showed complete clearance of skin lesions. Total eosinophil count was regarded as an excellent indicator for diagnosis, evaluation of therapeutic effects of IFN-gamma. IFN-gamma may be a suitable immunotherapy modality in the treatment of atopic dermatitis and futher studies for the action mechanism of IFN-gamma in atopic dermatitis might be needed.
Dermatitis, Atopic* ; Diagnosis ; Eosinophils ; Hematocrit ; Humans ; Immunoglobulin E ; Immunotherapy* ; Injections, Subcutaneous ; Interferon-gamma* ; Interleukin-4 ; Leukocytes ; Lymphocytes ; Platelet Count ; Reference Values ; Skin ; Skin Manifestations

A food allergy is an adverse health effect arising from a specific immune response that occurs reproducibly upon exposure to a given food. In those with food allergies that are thought to cause aggravation of eczema, food avoidance is important. The objective of this study was to research the nutritional status of patients with food allergies. A total of 225 subjects diagnosed with atopic dermatitis underwent a skin prick test as well as measurement of serum immunoglobulin E. Food challenge tests were conducted using seven food items: milk, eggs, wheat, soybeans, beef, pork, and chicken. At post-food challenge visits to the test clinic, participants completed a three-day dietary record, which included two week days and one weekend day, in order to evaluate energy intake and diet quality during the challenge. We analyzed nutrient intake based on differential food allergens. Subjects with a food allergy to milk showed lower intake of Ca, Zn, and vitamin B2, and subjects with a food allergy to egg showed lower intake of vitamin A, B1, B2, niacin, and cholesterol. Subjects with a food allergy to wheat and soybean showed lower intake of Ca, P, Fe, K, Zn, vitamin B2, vitamin B6, and niacin; and subjects with a food allergy to beef, pork, and chicken showed lower intake of Fe and higher intake of K, vitamin A, B2. Subjects with atopic dermatitis were lacking in several nutrients, including vitamin A and vitamin C. A greater number of food allergies showed an association with a greater number of nutrient intake deficiencies. Allergen avoidance is the basic treatment for atopic dermatitis. However, when the allergen is food, excessive restriction can lead to nutrition deficiency. Findings of this study suggest the necessity for enhanced nutritional education in order to provide substitute foods for patients with food allergies who practice food restriction.
Allergens ; Ascorbic Acid ; Chickens ; Cholesterol ; Dermatitis, Atopic* ; Diet Records ; Diet* ; Eczema ; Education ; Eggs ; Energy Intake ; Food Hypersensitivity ; Humans ; Immunoglobulin E ; Immunoglobulins ; Milk ; Niacin ; Nutritional Status* ; Ovum ; Riboflavin ; Skin ; Soybeans ; Triticum ; Vitamin A ; Vitamin B 6

IL-10 production by CD19(+)CD5(+) B cells was investigated, by determining the expression levels of CD19, a classical B cell marker. Peripheral mononuclear cells were stained with fluorescence-conjugated anti-CD5, anti-CD19, anti-IL-10, and Annexin V. Interestingly, IL-10-producing B cells were found to be localised within the CD19(low)CD5(+) B cell subset. Apoptotic changes were also observed mainly in CD19(low) cells among B cells. Thus, CD5(+) B cells should be classified as CD19(high) and CD19(low) cells, and the immunological significance of CD19 for the IL-10 production by CD5(+) B cells requires further studies.
Antigens, CD19/metabolism ; Antigens, CD5/metabolism ; Apoptosis/immunology ; B-Lymphocyte Subsets/cytology/*immunology ; Cell Separation ; Flow Cytometry ; Humans ; Interleukin-10/*biosynthesis

Foxp3 is a transcript factor for regulatory T cell development. Interestingly, Foxp3-expressing cells were identified in B cells, especially in CD19(+)CD5(+) B cells, while those were not examined in CD19(+)CD5(-) B cells. Foxp3-expressing CD5(+) B cells in this study were identified in human PBMCs and were found to consist of 8.5+/-3.5% of CD19(+)CD5(+) B cells. CD19(+)CD5(+)Foxp3(+) B cells showed spontaneous apoptosis. Rare CD19(+)CD5(+) Foxp3(+) regulatory B cell (Breg) population was unveiled in human peripheral blood mononuclear cells and suggested as possible regulatory B cells (Breg) as regulatory T cells (Treg). The immunologic and the clinical relevant of Breg needs to be further investigated.
Apoptosis ; B-Lymphocytes ; B-Lymphocytes, Regulatory ; Humans ; T-Lymphocytes, Regulatory

We examined the characteristics of food allergy prevalence and suggested the basis of dietary guidelines for patients with food allergies and atopic dermatitis. A total of 2,417 patients were enrolled in this study. Each subject underwent a skin prick test as well as serum immunoglobulin E (IgE) measurement. A double-blind, placebo-controlled food challenge was conducted using milk, eggs, wheat, and soybeans, and an oral food challenge was performed using beef, pork, and chicken. Food allergy prevalence was found among 50.7% in patients with atopic dermatitis. Among patients with food allergies (n = 1,225), the prevalence of non-IgE-mediated food allergies, IgE-mediated food allergies, and mixed allergies was discovered in 94.9%, 2.2%, and 2.9% of the patients, respectively. Food allergy prevalence, according to food item, was as follows: eggs = 21.6%, milk = 20.9%, wheat = 11.8%, soybeans = 11.7%, chicken = 11.7%, pork = 8.9% and beef = 9.2%. The total number of reactions to different food items in each patient was also variable at 45.1%, 30.6%, 15.3%, 5.8%, 2.2%, and 1.0% for 1 to 6 reactions, respectively. The most commonly seen combination in patients with two food allergies was eggs and milk. The clinical severity of the reactions observed in the challenge test, in the order of most to least severe, were wheat, beef, soybeans, milk, pork, eggs, and chicken. The minimum and maximum onset times of food allergy reactions were 0.2-24 hrs for wheat, 0.5-48 hrs for beef, 1.0-24 hrs for soybeans, 0.7-24 hrs for milk, 3.0-24 hrs for pork, 0.01-72 hrs for eggs, and 3.0-72 hrs for chicken. In our study, we examined the characteristics of seven popular foods. It will be necessary, however, to study a broader range of foods for the establishment of a dietary guideline. Our results suggest that it may be helpful to identify food allergies in order to improve symptoms in patients with atopic dermatitis.
Chickens ; Dermatitis, Atopic ; Eggs ; Food Hypersensitivity ; Humans ; Hypersensitivity ; Immunoglobulin E ; Immunoglobulins ; Milk ; Ovum ; Prevalence ; Skin ; Soybeans ; Triticum