变应性鼻炎舌下免疫治疗对患者生活质量的影响

目的探讨变应性鼻炎舌下免疫（sublingual immunotherapy,SLIT）治疗对患者生活质量的影响。方法将79例变应性鼻炎患者随机分为实验组40例与对照组39例,对照组给予抗组胺药物及鼻局部皮质类固醇药物治疗,实验组在此治疗基础上给予SLIT治疗。治疗后比较两组患者症状评分、药物评分及鼻炎生活质量情况。结果实验组在治疗3个月后症状评分和2个月后药物评分均较对照组明显降低;2年后实验组患者鼻炎生活质量明显优于对照组,组间比较,均P〈0.01,差异具有统计学意义。结论变应性鼻炎采用SLIT治疗,可明显减轻患者鼻部症状,减少用药量,改善患者鼻炎生活质量,是一种安全、有效的治疗方法。     

3 种常见尘螨分子进化关系的初步探讨

为探讨粉尘螨（Dermatophagoides farinae）、屋尘螨（Dermatophagoides pteronyssinus）和梅氏嗜霉螨（Euroglyphus maynei）的分类，采用PCR扩增获得粉尘螨1类(Der f 1)和2类变应原(Der f 2)的cDNA片段，经测序后推导氨基酸序列, 与GenBank中的屋尘螨Der p 1、Der p 2和梅氏嗜霉螨Eur m 1、Eur m 2氨基酸序列进行比对，分别构建1类和2类变应原分子进化树。结果显示变应原之间相似度，Der p 1与Eur m 1为86%，Der p 1与Der f 1为83%；Der p 2与Eur m 2为87%，Der p 2与Der f 2为67%。用变应原氨基酸序列构建分子进化树，1类变应原Der p 1与Eur m 1聚成一簇，2类变应原Der p 2与Eur m 2聚成一簇。结果表明屋尘螨和梅氏嗜霉螨亲缘关系较近，而与粉尘螨较远。     

舌下含服粉尘螨滴剂治疗多重过敏的过敏性哮喘的临床评价

目的观察标准化粉尘螨滴剂舌下特异性免疫治疗(SLIT)对多重过敏的过敏性哮喘(AS)的疗效及安全性。方法收集接受规则治疗2年且随访资料完整的轻、中度AS患者141例,按皮肤点刺试验结果及患者治疗意愿,分为单一尘螨过敏免疫治疗组(单一免疫组)41例、多重过敏免疫治疗组(多重免疫组)51例和多重过敏常规治疗组(多重常规组)49例。3组均应用小至中等剂量的吸入型糖皮质激素+长效β2受体激动剂,免疫组在此基础上给予粉尘螨滴剂SLIT,进行2年的随访观察,评价疗效。结果治疗2年后,多重免疫组的症状评分、用药评分显著低于多重常规组,ACT评分显著高于多重常规组(P0.05)。治疗2年后,多重免疫组的各项指标与单一免疫组比较差异均无统计学意义(P0.05)。多重免疫组与SLIT有关的不良反应发生率为9.80%,与单一免疫组类似(9.76%)。结论标准化粉尘螨滴剂综合药物治疗多重过敏的AS患者,较常规药物更能明显改善哮喘症状,减少药物使用,提高哮喘控制水平,可达到单一过敏患者的相似的治疗效果,未发生严重不良反应。     

Dust Mite Species and Allergen Concentrations in Beds of Individuals Belonging to Different Urban Socioeconomic Groups in Brazil

Background. Dermatophagoides pteronyssinus, Dermatophagoides farinae and Blomia tropicalis dust mites are among the most important agents of hypersensitivity reactions in human beings. However, a role of other mites in the etiology of these reactions has not yet been excluded.

Objectives. To investigate the nature of the dust mite fauna and the presence of Der p 1 (allergen 1 of Dermatophagoides pteronyssinus) and Blo t 5 (allergen 5 of Blomia tropicalis) on beds used by individuals with different socioeconomic backgrounds in Salvador, a major Brazilian city and to investigate possible associations of mite frequencies and allergen levels with (a) season of the year, (b) housing characteristics, (c) bed cleaning behaviors that could affect mite densities, and (d) allergy history.

Methods. Dust samples were collected from 459 beds of 101 residences from two groups with different socioeconomic levels (hereafter called wealthy and poor groups) in the city of Salvador, Brazil, for the identification of mite species and determination of Der p 1 and Blo t 5 levels. History of allergy was collected using the ISAAC phase I questionnaire.

Results. Eighty nine percent of the beds analyzed harbored at least one mite species. B. tropicalis was found in 71.8%, D. pteronyssinus in 39.9%, Cheyletus sp. in 33.9%, and Gohieria fusca in 21.1% of the beds. B. tropicalis was found with a similar frequency in beds of the two socioeconomic groups; D. pteronyssinus was found more frequently in the beds of the wealthy than of the poor group, whereas the reverse was observed with G. fusca. The concentrations of Der p 1 and Blo t 5 allergens exceeded the cut-off for sensitization of 2 μg/g of dust in 94.0% and 69.3% of the wealthy and poor group beds, respectively. No associations were found between history of allergy and mite species or between history of allergy and the concentrations of mite allergens.

Conclusions. The observation of B. tropicalis and D. pteronyssinus as the most frequently found mites is consistent with previous reports from tropical regions. The higher frequency of G. fusca in beds of individuals from the poor group than those from the wealthy group could be a consequence of different bed cleaning behaviors between the two groups.     

Effects of "systemic" budesonide concentrations on in vitro allergen-induced activation of blood mononuclear cells isolated from asthmatic patients

Blood levels of inhaled corticosteroids are significantly lower than those measured in the lung, but their concentration could still have anti-inflammatory effects. To determine whether budesonide, at concentrations similar to those obtained in blood after drug inhalation (10 ^?9 M), could downregulate the allergen-induced activation of mononuclear cells, we studied 21 atopic patients, sensitized to Dermatophagoides pteronyssinus (Der p). On blood mononuclear cells, isolated from these patients, incubated with Der p allergen extract and with or without budesonide, we evaluated: 1) the proliferative response of T cells; 2) the expression of two surface activation markers, the HLA-DR antigens and the interleukin (IL)-2 receptors; and 3) the release of cytokines known to modulate the allergic processes. Allergen-induced T-cell proliferation was associated with increased HLA-DR antigen and IL-2 receptor expression (P < 0.001), and with increased release of IL-2, interferon-gamma (IFN-γ), IL-1β, tumor necrosis factor-alpha (TNF-α), and granulocyte/macrophage colony-stimulating factor (GM-CSF). The addition of budesonide at the beginning of the cell cultures induced a dose-dependent inhibition of T-cell proliferation, still significant (P < 0.05) at the lowest concentrations tested (10 ^?9 and 10^?10 M). A significant inhibitory effect on T-cell proliferation was also present when budesonide (10 ^?9 M) was added to the cell cultures 3 or 5 days after the beginning of the cell cultures. In addition, budesonide 10^?9 M significantly decreased the expression of IL-2 receptors (P < 0.05), but not of HLA-DR antigens, and significantly reduced the release of IL-1β and GM-CSF (JP < 0.05), but not of IL-2, IFN-γ, and TNF-α. Thus, the blood concentrations of budesonide, after drug inhalation, may exert some anti-inflammatory effect, downregulating both “local” (through the bronchial circulation) and “systemic” allergen-specific immune reactions.     

A prospective safety-monitoring study of immunotherapy in mite-allergy patients with mass-units-standardized extract

González de la Cuesta C, Feijoo R, Rico P. A prospective safety-monitoring study of immunotherapy in mite-allergy patients with mass-units-standardized extract.
To determine the tolerance of an allergen extract standardized in mass units, we closely monitored the side-effects, during the buildup phase of immunotherapy treatment, in 88 patients with well-documented respiratory allergy to house-dust mite 'Dermatophagoides pteronyssinus'. Thirty-four patients '38.6%' suffered from moderate perennial rhinitis, and 54 had mild to moderate bronchial asthma '61.4%'. For the desensitizing treatment, we used a depot extract adsorbed in aluminum hydroxide of D. pteronyssinus 'Pangramin® Depot UM', biologically standardized and having the major allergens Der p 1 and Der p 2 quantified in micrograms. A total of 1244 doses were administered. All patients except one '98.9%' reached the expected maximum dose of 4 μg Der p 1. Only five patients suffered mild adverse reactions '5.7%'. All adverse reactions except one appeared to be related to the vial of maximum concentration: vial III '4 μg Der p 1'. Considering the number of patients who had adverse reactions and the frequency of adverse reactions per dose, we found no significant differences between rhinitis and asthma sufferers. We think that immunotherapy in doses of 4 μg Der p 1 and 2 μg Der p 2 is well tolerated and should not be avoided in mildly to moderately asthmatic patients when treating house-dust mite allergy.     

Skin test and crossreactivity studies with Euroglyphus maynei and Dermatophagoides pteronyssinus

Background The prevalence of sensitization to Euroglyphus maynei (E. maynei) in the United States has not been reported previously. Objectives To determine: (l) the prevalence of skin-test reactivity in allergic subjects to E. maynei compared to D. pteronyssinus, D. farinae, and B. tropicalis and (2) the allergenic crossreactivity between D. pteronyssinus and E. maynei. Methods Skin testing with extracts of B. tropicalis and E. maynei (1:50 w/v) and standardized D. pteronyssinus and D. farinae extracts (1:50 w/v; 10000 AU/mL) provided data on 250 subjects (87 males and 163 females) aged 9–77 years (mean age, 39.8 years) with possible allergic respiratory diseases. RAST inhibition assays were used to study crossreactivity between D. pteronyssinus and E. maynei. Results One hundred (40%) of 250 subjects had insignificant or no allergic diseases. Of the 150 allergic subjects (53 males, 97 females), 101 (67.3%) had a positive test (a percutaneous test with a weal diameter ≥ 3 mm larger than the saline control) to at least one mite species; 60.7%, 60.0%, 28.7%, and 52.0% reacted to D. farinae, D. pteronyssinus, B. tropicalis, and E. maynei, respectively; 40(26.7%) reacted to the four mite species. Positive tests to D. farinae, D. pteronyssinus, B. tropicalis, or E. maynei alone occurred in six (4.0%), four (2.7%), two (1.3%), and 0%, respectively. D. pteronyssinus and E. maynei showed moderately high crossreactivity in RAST inhibition assays. Conclusion There is a high rate of skin-test reactivity to E. maynei in Florida. Moderately high crossreactivity exists between E. maynei and D. pteronyssinus.     

Hyposensitization in asthmatics with mPEG modified and unmodified house dust mite extract

Forty-six asthmatics with verified allergy to the house dust mite, D. pteronyssinus (Dp), participated in a double-blind study comparing the effect of 2 years' hyposensitization with two different Dp extracts. Two groups received either monomethoxypolyethylene glycol modified (mPEG) Dp extract or the corresponding non-modified extract, and a third group acted as controls receiving no injections. Medicine consumption, symptom scores, and peak expiratory flow (PEF) were recorded daily from September to December prior to and after 6 and 18 months of treatment. Changes were calculated choosing changes greater than or equal to 10% as relevant. In addition, patients were asked to give their direct assessment of the clinical effect at the end of the study. After 6 months, there was an improvement in symptoms + medication in 11/14 of Dp-treated, 6/17 of the mPEG-Dp group (P greater than 0.05) and 3/15 of openly treated controls. Few patients had changed in PEF. During the second year, several Dp-treated relapsed and some controls improved. At the end of the study the same improvement rate was seen in all groups. Similarly, the retrospective questionnaire data did not disclose any significant differences between groups after 2 years. In conclusion, hyposensitization with unmodified Dp extract seemed to have a favourable short-term effect on bronchial symptoms + medication in the majority of patients. When mainly on maintenance dose, the beneficial effect was reduced. The mPEG modification of the extract had reduced not only allergenicity but also the clinical effect of equal doses. Changes in medicine and symptom scores only partly correlated to retrospective assessment, thus stressing the problems in this kind of evaluation.     

Selective restimulation of antigen or allergen preactivated T cells using OKT3 F(ab)2 results in the secretion of TH-1 or TH-2-like cytokine patterns

Background The synthesis of IgE is regulated by cytokines secreted from T-helper cells. The studies on cytokine secretion by peripheral blood mononuclear cells (PBMC) upon stimulation with antigen or allergen are ditficult due to low levels of cytokines, especially of inlerieukin-4 (IL-4).
Objective ln this study we tried lo establish a culture system, which could enable the measurement of the cytokine profiles in specifically activated cultures.
Methods Three methods to potentiate cytokine secretion were evaluated: PBMC from bee venom or house dust mite (Dermatophagoides pteronyssinus) allergic patients as well as normal subjects were stimulated either with the major bee venom allergen phosphoiipase A2 (PLA) or with the major D. pteronyssinus allergen (Der p 1) or with the control antigens tetanus toxoid (TT) and purified protein derivate (PPD). After 7 days of culture the cells were restimulated either wilh pkistie bound 0KT3 F(ab)2 monoclonal antibodies (MoAbs), with the appropriate antigen + antigen presenting cells or with IL-2. The secretion of cylokines (IL-4, IFNγ) was measured after restimulation of the cultures (day 8).
Results While OKT3 F(ab)2 was unable lo activate resting T cells, it could restimulate preactivaled cells. Restimulalion with OKT3 F(ab)2 induced higher IL-4 and IFN7 secretion than restimulation with IL-2 or antigen. TT and PLA stimulated a similar cytokine secretion prolile in normal and PLA allergic subjects with substantial levels of both lL-4 and IFNγ. In contrast, PPD induced virtually only IFNγ secretion. Der p 1 stimulated mainly IL-4 seerclion but also IFNγ production in some mite allergic palienis.
Conclusion We have established a cell culture system, which combines antigen specificity with a strong cytokine inducing signial provided by anti-CD3 MoAbs. TH-1 and TH-2 characteristic cytokine patterns can be observed in short-term PBMC cultures already after 8 days of culture.     

Cloning and sequencing of the group 6 allergen of Dermatophagoides pteronyssinus

Background The allergen Der p 6 from Dermatophagoides pteronyssinus has been described by substrate affinity as mite chymotrypsin. Objective The aim of this paper was to describe a cDNA clone encoding the allergen. Methods cDNA was cloned from a λ library using oligonucleotides published for Der p 6. Results The clone P6.1.1 had the N-terminal amino acid residues as reported for Der p 6, and at position 189 the Ser was conserved in chymotrypsin for substrate specificity as well as the catalytic triad of His57, Asp102 and Ser195 for serine proteases. The estimated Mr was 24.9K and it was 37% identical to the trypsin allergen Der p 3. Conclusion cDNA encoding Der p 6 has been described.