Takemasa Nakagawa

Changes of House Dust Mite-Specific IgE, IgG and IgG Subclass Antibodies during Immunotherapy in Patients with Perennial Rhinitis

House dust mite-specific IgE, IgG and IgG subclass antibody responses were evaluated during immunotherapy in perennial allergic rhinitis patients. It was found that IgG4 antibodies steadily increased during treatment, while IgG and IgG1 antibodies reached a plateau 6 months after the initiation of immunotherapy. IgE antibodies also increased during treatment. It was also found that the good clinical outcome was associated with the rate of increase of IgG4 antibodies, but not with IgG, IgG1 or IgE antibodies.

Bronchial Responsiveness to Mite Allergen in Atopic Dermatitis without Asthma

Eight patients with atopic dermatitis (AD) without a history of asthmatic episodes and 8 patients with mite-allergic bronchial asthma (BA) were subjected to bronchial inhalation challenge with a nonspecific stimulus (acetylcholine) and an immunologically specific stimulus (house dust mite allergen). AD patients had a significantly greater concentration of IgE (p less than 0.01) and antimite IgE antibody (p less than 0.05) than BA patients. Nonspecific bronchial hyperreactivities of AD patients distributed from normal to asthmatic range. After allergen challenge, all 8 AD patients and all 8 BA patients showed an immediate asthmatic response (IAR). The mite extract concentration to induce an IAR was significantly (p less than 0.01) greater in AD patients than in BA patients. A late asthmatic response was observed in 6 out of 8 BA patients, whereas it was not observed in any AD patient. Our results showed that AD patients are less reactive to a specific mite allergen than BA patients in spite of greater concentrations of antimite IgE antibody. They suggest that this difference in the bronchial reactivity to the allergen concerns the difference in the onset of clinical symptoms and that a certain level of bronchial hyperreactivity to the allergen is a prerequisite for the development of asthmatic symptoms.

The role of IgG4 as blocking antibodies in asthmatics and in bee keepers.

Sera from 40 asthmatic patients and from 77 bee keepers were evaluated by solid-phase radioimmunoassay for their allergen-specific IgG4 antibody levels. The results indicated that allergen-specific IgG4 antibodies become prominent upon repeated parenteral stimulation with antigen, i.e. immunotherapy and bee stings, and suggested the possible association of IgG4 with blocking antibodies in these allergic conditions.

IgG1 Antibodies to House Dust Mite (Dermatophagoides farinae) and Late Asthmatic Response

Thirteen asthmatic patients sensitive to mite were challenged by inhalation of an extract of mites (Dermatophagoides farinae). Seven showed dual bronchial reactions and 5 showed isolated immediate responses. No patient showed an isolated late reaction. Six of seven patients with dual reaction had higher IgG1 antibodies than the 5 patients with isolated immediate reaction when examined before the challenge. A similar result was obtained in terms of levels of immune complex. IgE, IgG4 and total IgG antibodies were not predictive for late reaction. These results suggest that there is a close correlation of the presence of high IgG1 antibodies with a propensity to develop late asthmatic responses. The meaning of this observation is discussed.

Case Report: The Longest-Lived Patient with Homozygous Familial Hypercholesterolemia Secondary to a Defect in Internalization of the LDL Receptor

The authors report the longest-lived patient with homozygous familial hypercholesterolemia, the seventh case of a defect in internalization of low-density lipoprotein (LDL). The patient is a 57-year-old man, whose plasma total cholesterol (TC) and LDL-cholesterol (LDL-C) concentrations were 465-660 mg/100 ml and 461 mg/100 ml, respectively, while his plasma high-density lipoprotein-cholesterol (HDL-C) was 13.6-16.9 mg/100 ml. He was the product of a consanguineous marriage, and his parents, brothers, and a sister had mild hypercholesterolemia. His coronary angiogram revealed diffuse coronary artery narrowing. Receptor studies revealed that his fibroblasts bound as much LDL as normal cells, but could not internalize or degrade LDL.

Circulating immune complexes in patients with house-dust-mite-sensitive bronchial asthma

Sera from forty patients with house‐dust‐mite‐sensitive bronchial asthma were examined for the presence of circulating immune complexes (CIC) by the sensitive and quantitative CIq solid‐phase radioimmunoassay (Clq‐SP) and a monoclonal rheumatoid factor solid‐phase radioimmunoassay (mRF‐SP). Compared to fifteen normal individuals, the asthmatic patients showed significantly higher mean values of Clq‐reactive materials; however, there was no difference between the results from the patients treated by immunotherapy using Dermatophagoides farinae extract and those not so treated. Moreover, immune complexes in eight patients before and after immunotherapy showed that the amount of the complexes tend to decrease during immunotherapy. Furthermore, the presence of complexes had no relationship with the amounts of mite‐specific IgG antibody. Similar results were also obtained in tests using mRF‐SP. These data suggest that complexes in the sera of the house‐dust‐mite‐sensitive asthmatic patients are not necessarily associated either with immunotherapy or with the mite‐specific IgG antibodies.

Inhibition of Allergic Bronchoconstriction in Guinea Pigs and in Asthmatics by the Leukotriene Antagonist ONO-1078

The effect of the leukotriene receptor antagonist ONO-1078 on experimental and clinical bronchial asthma was evaluated. It was found that this compound could inhibit antigen-induced bronchoconstriction in passively sensitized guinea pigs and leukotriene D4- and allergen-induced bronchial responses in normal and in asthmatic subjects. Clinical trials in patients with chronic bronchial asthma demonstrated its effectiveness in reducing hazardous symptoms like wheezing and dyspneic attacks.

Effect of Thromboxane A2 Synthetase Inhibitor on Immediate-Type Hypersensitivity Reactions

The effect of the thromboxane (TX) A2 synthetase inhibitor, OKY-046, on human leukocyte histamine release and bronchial hypersensitivity in asthmatic subjects was evaluated. It was found that OKY-046 inhibited IgE- and Ca2+ ionophore A23187-mediated leukocyte histamine release in a dose-dependent fashion (IC50: 1.0 and 3.0 X 10(-3) M, respectively) and that OKY-046 could diminish bronchial hypersensitivity, determined by leukotriene D4 inhalation, following a 2-week oral medication. These data suggest that the TXA2 synthetase inhibitor can produce favorable effects upon the course of immediate-type hypersensitivity reactions.