Hiroatsu Agata

Lymphocyte responses to food antigens in patients with atopic dermatitis who are sensitive to foods

The proliferative responses of peripheral blood mononuclear cells (PBMCs) to ovalbumin or bovine serum albumin in children with atopic dermatitis (AD) who are sensitive to hens egg or cows milk were significantly higher than responses of PBMCs of healthy children and hens egg- or cows milk-sensitive children with immediate symptoms. However, the percentages of positive RAST for hens egg or cows milk in the patients with AD were lower than percentages in the patients with immediate symptoms. In the patients with AD, there were no significant correlations between the proliferative responses of PBMCs and the RAST values. There were no significant differences of RAST scores among groups of patients having different degrees of severity of AD. The proliferative responses of PBMCs to ovalbumin or bovine serum albumin in patients with severe AD or moderate AD who were sensitive to hens egg or cows milk tended to be higher than responses of patients with mild AD, respectively, but there were no significant differences in those results. Taken together, the combination of RAST and the detection of proliferative responses of PBMCs to each food antigen is very useful in the diagnosis of hypersensitivity in children with AD who are sensitive to food allergens.

The role of T lymphocytes in patients with food-sensitive atopic dermatitis

The role of T lymphocytes was assessed in patients with food-sensitive atopic dermatitis (AD). T lymphocytes plus monocytes responded well to ovalbumin or bovine serum albumin (BSA) in children with AD who were sensitive to hens egg or cows milk compared with healthy children and children with immediate allergic symptoms who are sensitive to hens egg or cows milk. The responding cells were shown to be predominantly CD4+ T lymphocytes. Interleukin-2 activity and interferon-gamma concentrations in culture supernatants of ovalbumin-stimulated peripheral blood mononuclear cells (PBMCs) from patients with AD who were sensitive to hens egg were significantly higher than those of healthy children and patients sensitive to hens egg with immediate symptoms. Expression of Fc epsilon R II on B lymphocytes in cultures of ovalbumin-stimulated PBMCs from patients with AD was significantly higher than that of healthy children, but it tended to be lower than that of patients with immediate symptoms. These results suggest that, in patients with AD who are food sensitive, CD4+ T lymphocytes stimulated by food antigens secrete lymphokines such as interleukin-2 and interferon-gamma that are secreted from TH1 clones in mice, and express Fc epsilon R II on B lymphocyte that is induced by interleukin-4 secreted from TH2 clones in mice. Taken together, cell-mediated immunity may also occur in addition to IgE-mediated hypersensitivity in patients with food-sensitive AD.

Effect of elimination diets on food-specific IgE antibodies and lymphocyte proliferative responses to food antigens in atopic dermatitis patients exhibiting sensitivity to food allergens

Peripheral blood mononuclear cells (PBMCs) from patients with atopic dermatitis (AD) selected as being sensitive to hens egg or cows milk responded to food antigens, ovalbumin, or bovine serum albumin, with significantly enhanced DNA synthesis compared with the DNA synthesis in PBMCs from nonatopic control subjects and food-sensitive patients with immediate symptoms. Patients were treated with elimination diets. Symptoms of AD had been in remission during elimination diets. The levels of specific IgE antibodies to hens egg or cows milk decreased during elimination diets in patients with positive radioallergosorbent test (RAST). In patients with negative RAST, specific IgE antibodies remained negative during elimination diets. The proliferative responses of PBMCs to food antigens also decreased during elimination diets in patients with proliferative responses before elimination diets. Taken together, specific IgE antibodies to food antigens are useful indexes of the effect of elimination diets in food-sensitive patients with AD and positive RAST, and proliferative responses of PBMCs to food antigens are useful indexes of the effect of elimination diets in food-sensitive patients with AD and proliferative responses of PBMCs.

Predictive values of cord blood IgE and cord blood lymphocyte responses to food antigens in allergic disorders during infancy

Proliferative response of cord blood lymphocytes stimulated twice by food antigens and cord blood IgE concentration were measured in 131 full-term newborn infants for the prediction of allergic disorders. Through the follow-up study for 2 1/2 years, the value of stimulation index in proliferative response of cord blood lymphocytes to ovalbumin or bovine serum albumin was greater than 1.5 in 17 (sensitivity 53.1%) of 32 infants in whom allergic disorders developed and less than 1.5 in 81 (specificity 81.8%) of 99 infants who had no allergic disorders (cutoff limit of stimulation index 1.5). The sensitivity was increased (71.9%) by the combination of the cord blood IgE concentration (cutoff limit 1.0 IU/ml) and proliferative response of cord blood lymphocytes to food antigens (cutoff limit of stimulation index 1.5). The combination of the cord blood IgE concentration and proliferative response of cord blood lymphocytes to food antigens is useful for the prediction of allergic disorders. Interleukin-2 production of cord blood lymphocytes stimulated with food antigens was also measured in 24 newborn infants. Interleukin-2 activity in culture supernatants of ovalbumin- or bovine serum albumin-stimulated cord blood lymphocytes correlated well with proliferative response of cord blood lymphocytes to ovalbumin or bovine serum albumin.

Pulmonary hemosiderosis with hypersensitivity to buckwheat

BACKGROUND Adverse reactions after ingesting buckwheat are known to be IgE-mediated. Further, hypersensitivity reactions may be involved in some patients with pulmonary hemosiderosis related to cow milk sensitivity. We, however, encountered a patient with pulmonary hemosiderosis related to buckwheat protein without high levels of buckwheat-specific IgE antibodies. OBJECTIVE The aim of this study was to investigate the mechanisms. METHODS RAST for anti-buckwheat IgE, skin prick test, skin patch test, and proliferative responses of peripheral blood mononuclear cells to buckwheat were investigated in this patient. RESULTS RAST values for buckwheat protein were negative, and skin prick test for buckwheat protein also gave negative results. On the other hand, skin patch testing for buckwheat protein elicited positive responses. Further, peripheral blood mononuclear cells of our patient responded to buckwheat protein. CONCLUSIONS Our patient had pulmonary hemosiderosis related to non-immediate buckwheat protein hypersensitivity.

Improvement of food‐sensitive atopic dermatitis accompanied by reduced lymphocyte responses to food antigen following natural measles virus infection

Five patients with atopic dermatitis (AD) who were sensitive to hens egg were observed before and after natural measles virus infection. Within 4 weeks of natural measles virus infection, the eczematous lesions clearly improved in four of the five patients in whom neither offending foods were eliminated, nor anti‐allergic drugs, systemic steroids and steroid ointment administered. This was accompanied by reduced proliferative responses of peripheral blood mononuclear cells (PBMCs) to ovalbumin (OA). Another patient showed a transient improvement of AD symptoms, from severe to mild, and thereafter returned to severe accompanied by increased proliferative responses of PBMCs to OA. Radioallergosorbent test (RAST) scores for hens egg in all five patients did not change in each level in each patient, except the transiently decreased RAST scores for hens egg in one patient, after the infection. Thus, in patients with AD who are sensitive to food, the improvement of AD symptoms that appeared within 4 weeks of natural measles virus infection was related to reduced proliferative responses of PBMCs to the food antigen following the infection.

Timing of onset of allergic symptoms as a response to a double-blind, placebo-controlled food challenge in patients with food allergy combined with a radioallergosorbent test and the evaluation of proliferative lymphocyte responses.

The timing of onset of allergic symptoms in a double-blind, placebo-controlled food challenge (DBPCFC) was combined with a radioallergosorbent test (RAST) and evaluation of proliferative responses of peripheral blood mononuclear cells (PBMCs) in 27 atopic dermatitis patients with hens egg allergy. Of the 27 patients, 11 showed reactions within 2 h (immediate group), and 16 showed reactions after more than 2 h (nonimmediate group) after ingestion of hens egg. The RAST scores for hens egg in the immediate group were significantly (p < 0.01) higher than those in the nonimmediate group, while the proliferative responses of PBMCs to ovalbumin in the nonimmediate group were significantly (p < 0.01) higher than those in the immediate group. These results suggest that the RAST values are related to immediate allergic symptoms in DBPCFC and the proliferative responses of PBMCs are related to nonimmediate allergic symptoms in DBPCFC. The timing of onset of allergic symptoms in DBPCFC will render DBPCFC more useful in the diagnosis of food allergy, including the late-onset reactions to foods.

Interferon-γ and interleukin-4 production of ovalbumin-stimulated lymphocytes in egg-sensitive children

BACKGROUND The causal relation between egg allergy and cytokines derived from lymphocytes is unknown. OBJECTIVE Interferon-gamma (IFN-gamma) and interleukin-4 (IL-4) production of ovalbumin-stimulated and interleukin-2 (IL-2)-stimulated peripheral blood mononuclear cells from egg-sensitive patients was investigated and compared with that of stimulated peripheral blood mononuclear cells from nonatopic healthy children. METHODS Peripheral blood mononuclear cells from egg-sensitive patients and nonatopic healthy children were cultured with ovalbumin and IL-2 for seven days. The IFN-gamma and IL-4 concentrations in culture supernatants of the peripheral blood mononuclear cells were investigated. RESULTS The levels of IFN-gamma production of only IL-2-stimulated or both ovalbumin-stimulated and IL-2-stimulated peripheral blood mononuclear cells from egg-sensitive patients with atopic dermatitis was significantly higher than that of healthy children and that of egg-sensitive patients with immediate allergic symptoms. CONCLUSIONS Increased IFN-gamma production by lymphocytes after IL-2 and antigen stimulation has important implications for the mechanism of food-sensitive atopic dermatitis.

Proliferative responses of CD4+ T‐cell population to ovalbumin in patients with atopic dermatitis who are sensitive to hen eggs

Proliferative responses of peripheral blood mononuclear cells and T cells with monocytes to ovalbumin were significantly higher than those of B cells with monocytes to ovalbumin in patients with atopic dermatitis (AD) who were sensitive to hen eggs. The CD4+ T‐cell/CD8+ T‐cell ratios (the values obtained by dividing the maximum stimulation index of CD4+ T cells with monocytes to ovalbumin by the maximum stimulation index of CD8 + T cells with monocytes to ovalbumin) were significantly higher in AD patients sensitive to hen eggs than in non‐atopic healthy controls. The proliferative responses of CD4+ T cells with monocytes to ovalbumin were more intensive than those of CD8+ T cells with monocytes in patients with AD sensitive to hen eggs compared with non‐atopic healthy controls. These results suggest that the cells responding to ovalbumin are predominantly CD4+ T cells. However, there was no relationship between the stimulation index of proliferative responses of peripheral blood mononuclear cells to ovalbumin and RAST scores for hen eggs. Thus it is possible that the majority of the CD4+ T cells which respond to ovalbumin are not CD4+ helper T cells for IgE production.

Suppression of Proliferative Responses of Lymphocytes to Food Antigens by an Anti-Allergic Drug, Ketotifen Fumarate, in Patients with Food-Sensitive Atopic Dermatitis

Experimental studies have shown that ketotifen fumarate inhibits reaginic antibody-mediated hypersensitivity reactions. In this study, the proliferative responses of peripheral blood mononuclear cells (PBMCs) to ovalbumin (OA) in children with atopic dermatitis (AD), who are sensitive to hens egg, were significantly higher than those of healthy children. The proliferative responses of PBMCs to OA were dose-dependently inhibited by ketotifen in patients with hens egg-sensitive AD. Moreover, the inhibition resulted from the effects of ketotifen on T cells. In contrast, the proliferative responses of PBMCs to phytohemagglutinin and tetanus toxoid were not inhibited by ketotifen. These results suggest that ketotifen inhibits food antigen-specific proliferative responses of PBMCs in patients with food-sensitive AD.