The Subclass Nature and Clinical Significance of the IgG Antibody Response in Patients Undergoing Allergen-Specific Immunotherapy

The purpose of this paper is to discuss the methodological difficulties in quantitation of human IgG subclass antibodies to allergens, to describe the subclass nature of the IgG antibody response in patients undergoing allergen-specific immunotherapy, and to discuss the possible immunological functions and clinical significance of allergen-specific IgG antibodies of different subclasses. Based on results obtained by use of assays with documented specificity it is concluded that the IgG antibody response during allergen-specific immunotherapy is IgG1 and IgG4 restricted, although low levels of IgG2 and IgG3 antibodies to some allergens may occur. In most patients the early IgG antibody response is IgG1 dominated and the late IgG4 dominated. A too early or too pronounced IgG4 dominated antibody response seems to indicate a poor clinical outcome of immunotherapy with inhalant allergens, whereas a pronounced early IgG1 antibody production has been found to be associated with a decrease in synthesis of IgE antibodies to an insect venom. It is therefore proposed that an early IgG1 dominated response is necessary to induce suppression of the ongoing IgE antibody production, which in its turn may be a prerequisite for long-lasting clinical effect. The possibility of induction of an early IgG1 dominated response in every patient by use of alternative immunotherapy procedures is discussed.     

Major allergens of date palm (Phoenix dactylifera L.) pollen

The IgE-binding components of date palm ( Phoenix dactylifera L.) pollen were determined by ELISA and Western blotting in atopic patients in order to identify its major allergens. From a pool of previously identified allergenic fractions and sera from 15 skin-test-positive, atopic subjects, four components of 12, 14.4, 57, and 65–67 kDa were found to bind IgE in 80–93% of sera. Two other components of molecular masses 28–30 and 37–40 kDa also bound 60–80 % of atopic sera. The immunologic specificity of date-pollen allergen that induced antibody response in sera of atopic patients was confirmed with ELISA. Furthermore, most of the reactivity in pooled positive atopic serum and antiserum raised in rabbits was eliminated after the sera were absorbed with the allergen. IgG immunoblot analyses showed varying degrees of cross-reactivity with common local allergens, notably Bermuda grass, but were generally of low intensity. These results indicate that date pollen has six major allergens with the 12, 14.4, 57, and 65–67 kDa bands binding 80–93%, and the 28–30 and 37–40 kDa bands 60–80% of atopic sera. We propose that these major allergens be assigned the notations Pho d I to Pho d VI in the order listed.     

Exposure to formaldehyde and phenol during an anatomy dissecting course: sensitizing potency of formaldehyde in medical students

BACKGROUND: The sensitizing potency of formaldehyde and phenol during anatomy dissecting was investigated. The objective was to determine whether exposure induces specific IgE or IgG against formaldehyde-albumin or phenol-albumin. METHODS: In 27 medical students, specific IgE against formaldehyde-albumin by RAST plus ELISA and specific IgE against phenol-albumin by ELISA were assessed. In addition, specific IgG against formaldehyde-albumin was assessed in 23 students. Symptoms before and during dissecting were assessed, and indoor formaldehyde and phenol were measured. RESULTS: Mean indoor formaldehyde was 0.265 +/- 0.07 mg/m3, and mean indoor phenol was 4.65 +/- 2.96 mg/m3. Specific IgE/IgG against formaldehyde-albumin was not found at the beginning. Four students developed specific IgE against formaldehyde-albumin (RAST classes of > or =2.0), and all four also had specific IgE in the ELISA, but IgG against formaldehyde-albumin was not found. Specific IgE against phenol-albumin was not seen. Itch and paresthesia of the hands (P<0.00001), dizziness (P<0.008), burning eyes (P<0.01), headache, sneezing, epistaxis, gingival bleeding, oral or pharyngeal itch, and shortness of breath were experienced. CONCLUSIONS: Formaldehyde exposure during dissecting may induce specific IgE, but not IgG, against formaldehyde-albumin. Sensitization did not correlate with symptoms.     

Azelastine and allergen transduction signal in MC9 mast cells

Summary MC9 mast cells, sensitized with monoclonal IgE antibody specific for 2,4-dinitrophenyl (DNP) group, were exposed to DNP-BSA and the pH and cytosolic calcium signals were recorded by using the fluorescent probes BCECF and Fura-2 respectively. DNP-BSA induced cell alkalinization was fully inhibited by azelastine with IC₅₀ (1.6±0.5 mol/l, mean±SEM, n = 5) similar to that required to inhibit histamine release (1.4 mol/l), Conversely, high azelastine concentrations (> 100 mol/l) were required to inhibit DNP-BSA-dependent cell calcium mobilization (IC₅₀200 mol/l, n = 3). Amiloride, but not the H₁ histamine antagonist pyrilamine, was able to inhibit the DNP-BSA induced pH signal. In acidified mast cells, azelastine potently inhibited Na⁺:H⁺ exchange activity (IC₅₀ = 7.7±3.6 × 10^–6 M, mean±SEM, n = 3). Conversely, in mouse spleen lymphocytes azelastine was unable to inhibit the amiloride-sensitive pH signal induced by concanavalin A. In conclusion, the inhibition of histamine release by azelastine is not due to an interference with the cytosolic calcium signal. Conversely, azelastine potently antagonized the allergen-dependent Na⁺: H⁺ exchange activation, suggesting an action on the protein kinase C signaling pathway. Correspondence to: R. P. Garay at the above address     

联合抗过敏疗法对急性乙型肝炎病人的疗效观察

[目的 ]阐明Ⅰ型变态反应与急性乙型肝炎关系 .[方法 ]将 42例急性乙型肝炎病人随机分为治疗组和对照组 ,并观察了联合抗过敏疗法对急性乙型肝炎的疗效 .[结果 ]治疗组行联合抗过敏疗法后血清内谷丙转氨酶和总胆红素均比治疗前明显降低 ,而对照组治疗前后无明显变化 ;治疗组谷丙转氨酶及总胆红素复常天数明显短于对照组 .[结论 ]联合抗过敏疗法对急性乙型肝炎疗效显著 ,从而间接证明了免疫球蛋白E及其介导的Ⅰ型变态反应在急性乙型肝炎发病机理中的致病作用 .     

急性乙型肝炎病人血清免疫球蛋白E水平与T淋巴细胞亚群的检测

[目的 ]观察急性乙型肝炎病人血清总免疫球蛋白E水平与T淋巴细胞亚群的关系 .[方法 ]应用间接酶联免疫吸附法测定急性乙型肝炎病人和正常人血清总免疫球蛋白E水平 ,应用APAAP法检测T淋巴细胞亚群 .[结果 ]急性乙型肝炎病人血清总免疫球蛋白E含量高于正常人 ;而病人T淋巴细胞亚群中的CD4 /CD8比值较正常人明显降低     

白细胞介素-4对哮喘患者血清IgE的影响

目的：探讨白细胞介素－４（ＩＬ－４）在过敏性支气管哮喘发病机制中对ＩｇＥ的作用。方法：试验采用双盲、交叉、随机、安慰剂对照的设计方法,给予８例过敏性哮患者吸入２０μｇ人重组ＩＬ－４或载体溶液,并分别于吸入前、吸入后２,２４,４８ｈ测定患者血清ＩｇＥ水平。结果：吸入载体溶液与吸入ＩＬ－４前的血清总ＩｇＥ基础值无显著差异（ｐ〉０．０５）,吸入后各时点血清总ＩｇＥ亦无明显变化（ｐ〉０．０５）。结论：吸入     

咳嗽变异型哮喘患儿sICAM-1的研究

目的探讨可溶性细胞间粘附分子-1(sICAM-1)在过敏性咳嗽中的意义。方法采用ELISA方法和放射免疫技术,测定30例咳嗽变异型哮喘、41例支气管哮喘患儿的sICAM-1和总IgE,同时测嗜酸、嗜碱性细胞绝对计数和过敏原皮试。结果咳嗽变异型哮喘患儿和支气管哮喘发作期患儿的嗜酸、嗜碱性细胞绝对计数相似,但sICAM-1和总IgE均较正常对照组明显增高。咳嗽变异型哮喘患儿的过敏原皮试反应的阳性率、阳性种类和程度均较支气管哮喘发作期为低。结论sICAM-1和总IgE、过敏原皮试均可作为咳嗽变异型哮喘的诊断指标。     

Interleukin-3-dependent potentiation of IgE responsiveness in mouse basophils

Basophils produce interleukins (IL)-4 in response to various stimuli and may contribute to type 2 immune responses to various infections and allergens. We found that resting basophils freshly isolated from mice produce IL-4 in response to IL-3 but not to high-affinity Fc receptor (FcεRI) cross-linking (CL), yet both required the immunoreceptor tyrosine-based activation motif (ITAM) containing adaptor Fc receptor γ-chain (FcRγ), while basophils activated in vitro by IL-3 become responsive to FcεRI CL. Acquisition of responsiveness to FcεRI CL occurred upon infection with Trichinella spiralis or administration of superantigen. Because cultured basophils return to a quiescent state upon starvation with IL-3 with surface FcεRI levels unchanged, this acquisition is reversible and probably reflects intracellular events requiring protein synthesis. Interestingly, similar activation-associated acquisition was observed for responsiveness to other stimuli, including CD200R3 CL, which is known to signal via DAP-12, and the allergen protease papain. This acquisition of responsiveness to FcεRI CL was inhibited by Jak inhibitor. Thus, the IL-3 signal bifurcates downstream of Jak, into two distinct pathway, one leading to IL-4 production and the other to render basophils competent to respond to stimuli dependent on ITAM-containing adaptors DAP12 and FcRγ for IL-4 production.     

In situ dormancy of B lymphocytes programmed for an IgE antibody response and their sudden release from unresponsiveness under in vitro conditions

Priming of CBA/J mice with different doses of antigen has aprofound effect on the ratio of IgE versus IgG antibodies appearingupon Immunization. Repeated injections of minute doses induceIgG and high titers of IgE antibodies. Large doses elicit ahigh IgG but a very low IgE antibody titer. In order to studythe modalities for activation and inactivation of IgE-producingB cells, an in vitro culture system was established in whichspleen cells from animals primed with keyhole limpet hemocyaninwere re-stliulated with antigen. In contrast to the expectationfrom the in vivo situation, spleen cells from animals Immunizedwith large doses of antigen and virtually lacking IgE antibodiesproduce high amounts of IgE antibodies upon re-stimulation invitro. The titers in spleen cell cultures from mice primed withminute doses remain proportional to the response measured asserum antibodies. In accordance with the induction of high amountsof IgE antibodies in spleen cell cultures from mice primed withlarge doses, the frequency of IgE antibody-secreting cells wasraised drastically, 1000-fold. The in vitro response is a trueanamnestic response. The sudden appearance in high frequencyof IgE antibody-forming cells among spleen cells isolated fromprimed mice which have high IgG but virtually no IgE antibodytiters is as yet unexplained and the origin of the B memorycells has not yet been traced. The answer might be crucial forour understanding of the down-regulation of the IgE Immune responses.