青霉素过敏病人血清特异性IgE与IgG、IgG3、IgG4

目的：IgE抗体在青霉素过敏反应中的地位已得到公认,IgG抗体的作用也日益受到重视。IgG分为IgG1、IgG2、IgG3和IgG4四种亚类。IgG与过敏反应的关系至今尚未明确,可能与其亚类有关。为探讨IgG及其亚类在青霉素过敏反应中的作用,分析与特异性IgE抗体的关系,以期为青霉索过敏反应的诊断及防治提供理论依据。方法：采用放射免疫吸附试验（RAST）检测青霉素过敏病人血清中8种抗原决定簇（BPO—PLL、BPA—PLL、PVO-PLL、PVA-PLL、APO—PLL、APA-PLL、AXO—PLL、AXA-PLL）特异性IgE抗体。采用酶联免疫吸附试验（ELISA）检测青霉素过敏病人血清中8种特异性IgG、IgG3和IgG4抗体。结果：164例过敏病人中,IgG、IgG3和IgG4的阳性率分别为28．05％、13．39％、12．80％。其中,迟发过敏反应组的IgG3阳性率显著高于速发过敏反应组（P〈0．05）。皮试阴性组的IgG阳性率显著高于皮试阳性组（P〈0．01）,并且皮试阴性用药后出现过敏症状组的IgG阳性率显著高于皮试阳性同时出现过敏症状组（P〈0．05）。IgG在主要抗原决定簇中的阳性率显著高于次要抗原决定簇（P〈0．01）。     

放射过敏原吸附试验检测青霉素过敏病人血清中特异性IgE抗体

采用放射过敏原吸附试验 (RAST)检测 13 0例青霉素过敏病人血清中 9种主要和次要抗原决定簇 (BPO ,AXO ,APO ,PVO ,FLUO ,BPA ,AXA ,APA ,PVA)特异性IgE抗体 ,以探讨青霉素过敏反应机制并改进过敏反应诊断方法。结果 13 0例过敏病人中有 44例 (3 3 .8% )特异性IgE抗体呈阳性 ,其中 86例皮试阳性和 44例有过敏史病人血清特异性IgE抗体阳性率分别为 2 4.4%和 5 2 .3 % ,后者较前者明显升高 (P <0 .0 5 )。 13 0例过敏病人主要抗原决定簇 (BPO ,AXO ,APO ,PVO ,FLUO)和次要抗原决定簇 (BPA ,AXA ,APA ,PVA)IgE抗体阳性率分别为 19.2 %和 2 7.6% ,后者明显高于前者 (P <0 .0 5 )。根据皮试或发生过敏反应与抗体测定时间间隔分为 4个时间段 :即刻、3 0d内、3 0d～ 2年和 2年以上 ,皮试阳性病人各时间段特异性IgE抗体阳性率分别为42 9%、2 8 6%、18 8%和 10 5 % ;有过敏史病人分别为 87.5 %、71.4%、5 3 .3 %和 2 1.4%。研究结果提示 ,次要抗原决定簇在过敏反应中发挥着重要作用 ,且过敏病人特异性IgE抗体随时间延长呈下降趋势。     

青霉素过敏病人与头孢菌素的交叉过敏反应

目的：探讨青霉素过敏病人与头孢菌素交叉过敏反应的情况。方法：采用放射性过敏原吸附试验（RAST）检测420例青霉素过敏病人体内8种青霉素特异性IgE抗体（BPO、PVO、APO、AXO、BPA、PVA、APA和AXA）以及11种头孢菌素特异性IgE抗体（CEXO、CLO、CEZO、CPZO、CTO、CZO、CXO、CEXA、CLA、CEZA、CPZA）。结果：头孢菌素特异性IgE抗体检出阳性率随所检测抗原决定簇种类的增多而增高,并且检测5种与检测11种抗体所得阳性率无显著性差异（P〉0．05）。420例病人中有73例（t7．38％）存在青霉素与头孢菌素交叉过敏反应,有95例（22．62％）至少一种头孢菌素特异性IgE抗体呈阳性。青霉素特异性IgE抗体阳性组头孢菌素特异性IgE抗体阳性率显著高于其抗体阴性组（P〈0．01）。对具有相同或相似侧链结构抗生素的次要抗原决定簇特异性IgE抗体的相关性分析发现,APA-IgE与AXA-IgE,APA-IgE与CEXA—IgE,AXA—IgE与CEXA—IgE,BPA-IgE与CLA—IgE水平均正相关（P〈0．05）,且氨苄西林、阿莫西林抗体阳性组头孢氨苄抗体阳性率显著高于其抗体阴性组（P〈0．05）。结论：青霉素过敏病人存在与头孢菌素的交叉过敏反应,交叉过敏反应率达17．38％。     

青霉素过敏病人嗜碱性粒细胞表面CD63的变化

目的评价嗜碱性粒细胞表面CD63在诊断青霉素过敏反应中的价值。方法采用流式细胞过敏原刺激试验(FAST)的方法检测43例青霉素过敏病人血中嗜碱性粒细胞在9种抗原刺激后(PG、PV、AMP、AX、6-APA、PHA、PHOA、PHPG、NPG)表面CD63的变化。采用放射免疫吸附试验(RAST)和酶联免疫吸附试验(ELISA)检测8种特异性IgE和IgG抗体。结果43例青霉素过敏病人中有28例为CD63阳性,15例健康对照受试者中有1例阳性。其敏感性为65.12%,特异性为93.33%。CD63和特异性IgE在皮试阳性组的敏感性高于特异性IgG(P<0.05),并且在IgE阳性组中,CD63的阳性率高于特异性IgG(P<0.05)。结论CD63可作为检测青霉素类过敏反应嗜碱性粒细胞特异性激活标志物。     

青霉素过敏病人血清食入性、气源性致敏原特异性IgE抗体

目的：为进一步研究青霉素类过敏反应的机制,探讨青霉素过敏反应与食入性、气源性致敏原过敏反应的相关性。方法：本研究采用放射过敏原吸附试验（RAST）检测219例青霉素过敏病人血清8种普通过敏原（包括4种食入性和4种气源性）和8种青霉素主、次要抗原决定簇。结果：青霉素过敏病人中,至少一种青霉素类药物特异性IgE抗体阳性率为62．10％,至少一种普通过敏原IgE抗体阳性率为42．92％,食入性致敏原特异性IgE抗体阳性率和气源性致敏原特异性IgE抗体阳性率分别为33．33％和23．29％。青霉素抗体阳性病人组中,食入性致敏原IgE抗体阳性率显著高于抗体阴性组（P〈0．05）,且食入性致敏原IgE与青霉素IgE呈正相关（r=0．213,P=0．002）;气源性致敏原IgE抗体阳性率在两组问无显著性差异（P〉0．05）,且气源性致敏原IgE与青霉素IgE无相关性（r=0．119,P=0．08）。结论：食入性致敏原对IgE介导的青霉素过敏病人的致敏性较高。     

青霉素类抗生素过敏反应机制及诊断的新近研究进展

青霉素抗原决定簇有多样性，包括主要和次要抗原决定簇、侧链抗原决定簇以及由β－内酰胺环与侧链结合而成等。青霉素过敏患者血清中存在核特异性抗体和侧链特异性抗体等，有的可识别母核结构，有的仅识别侧链结构，亦即青霉素类抗生素间可存在完全交叉过敏反应，也可存在部分交叉、甚至无交叉过敏反应。对过敏患者可根据药物结构尤其是侧链结构恰当选择本类药物。T细胞在青霉素类过敏反应中起着重要作用，过敏患者体内存在2种T细胞系，一种对识别的药物具有高度选择性；另一种选择性较差，可识别多种药物。药物特异性T细胞主要识别青霉素类的侧链和双环结构，通过分泌多种细胞因子而参与并调节过敏反应。青霉素过敏反应的诊断仍以皮试为主，但其敏感性和特异性较差，存在假阴性和假阳性，增加皮试剂的成分可提高其敏感性。体外检测有放射过敏原吸附试验（RAST）、酶联免疫吸附试验（ELISA）和淋巴细胞转化试验（LTT）等，以放射过敏原吸附试验应用较多，以上方法具有较高的敏感性和特异性，但操作过程复杂，临床难以完全取代皮试，可与皮试结合应用。     

青霉素与头孢菌素交叉过敏反应及特异性抗体

目的：探讨青霉素与头孢菌素交叉过敏反应机制,评价侧链结构在交叉过敏反应中的地位。方法：采用RAST分别检测了420例青霉素过敏病人和34例头孢菌素过敏病人体内8种青霉素特异性IgE抗体（BPO、PVO、APO、AXO、BPA、PVA、APA和AXA）以及11种头孢菌素特异性IgE抗体（CEXO、CLO、CEZO、CPZO、CTO、CZO、CXO、CEXA、CLA、CEZA、CPZA）,采用RAST抑制试验检测了4例典型过敏病人特异性抗体对多种药物及其不同侧链和母核结构的识别位点。结果：头孢菌素过敏病人血清中头孢菌素特异性IgE抗体阳性率显著高于青霉素过敏病人（P〈0．01）。特异性IgE抗体检出阳性率随所检测抗原决定簇种类的增多而增高,并且检测9种与检测19种抗体所得阳性率无显著性差异（P〉0．05）。454例病人中有90例（19．82％）存在青霉素与头孢菌素抗生素交叉过敏反应。     

青霉素过敏病人血清特异性IgE和IgG抗体

采用放射过敏原吸附试验(RAST)和酶联免疫吸附试验(ELISA)测定52例青霉素过敏病人血清特异性IgE、IgG抗体，进一步探讨青霉素过敏反应机制。结果 52例过敏病人特异性IgE、IgG抗体的阳性率分别为50％和44．2％，若RAST与ELISA联合检测，IgE和IgG抗体总阳性率增至63.5％。荨麻疹组BPO—IgG水平高于过敏性休克组(P＜0.01)，过敏性休克病人BPA—IgG水平明显高于BPO—IgG(P＜0．01)，荨麻疹组内BPO—IgE水平与BPA—IgE无显著差异(P＞0．05)。但均比过敏性休克组高。研究结果提示，荨麻疹与BPO—IgE和BPA—IgE关系密切，过敏性休克与BPO—IgE和BPA—IgG关系密切；同时检测IgE和IgG抗体，可提高诊断阳性率。     

头孢菌素过敏病人与青霉素的交叉过敏反应

目的：探讨头孢菌素过敏病人与青霉素交叉过敏反应的情况,并改进头孢菌素过敏反应的诊断方法,方法：采用放射性过敏原吸附试验（RAST）检测34例头孢菌素过敏病人体内8种青霉素特异性IgE抗体（BPO、PVO、APO、AXO、BPA、PVA、APA和AXA）以及11种头孢菌素特异性IgE抗体（CEXO、CLO、CEZO、CPZO、CTO、CZO、CXO、CEXA、CLA、CEZA、CPZA）。结果：特异性IgE抗体检出阳性率随所检测抗原决定簇种类的增多而增高,并且检测5种与检测11种抗体所得阳性率无显著性差异（P〉0．05）。34例病人中有32例（94．12％）至少一种头孢菌素特异性IgE抗体呈阳性,18例（52．94％）存在青霉素与头孢菌素交叉过敏反应,19例（55．88％）至少一种青霉素特异性IgE抗体呈阳性。     

青霉素过敏患者白细胞介素13血清浓度及其基因多态性

目的探讨青霉素类抗生素过敏反应与白细胞介素13(IL-13)及其基因多态性的关系。方法采用ELISA检测51例青霉素过敏患者和20例健康人血清IL-13浓度,放射过敏原吸附试验检测血清中8种青霉素特异性IgE抗体水平,聚合酶链反应-限制性片段多态性分析法检测IL-13+2044G/A多态性位点的基因型。结果青霉素过敏患者血清IL-13浓度的中位数为19.80(0.10,50.00)ng·L-1,显著高于健康对照组1.68(0.20,22.90)ng·L-1,而且血清IL-13浓度随着青霉素特异性IgE抗体阳性种类的增加而增加。IL-13+2044G/A多态性位点等位基因频率与健康对照组无明显差异,GG基因型患者血清氨苄西林主要抗原决定簇IgE抗体水平显著高于GA和AA基因型患者。结论青霉素过敏反应可能与血清IL-13浓度升高有关;IL-13+2044G/A基因多态性可能与某些青霉素特异性IgE抗体浓度升高有关。     

Penicillin Allergy Skin Testing: What Do We Do Now?

Drug-induced anaphylaxis remains a relatively infrequent event. However, penicillin and associated beta-lactam antibiotics remain a primary cause of anaphylaxis. Penicillin allergies are undoubtedly overreported, and patients with suspected penicillin allergy can be treated with antibiotic alternatives. Penicillin allergy skin testing is a simple and effective way to identify true penicillin allergy. Skin testing involves testing for both major and minor determinants and should be conducted in a facility with available life-support equipment. The commercial major determinant product, benzylpenicilloyl-polylysine, was removed from the market in 2004; this action compromised the ability of clinicians to evaluate a patient's likely response to penicillin therapy. Alternatives to skin testing include laboratory synthesis of major determinants, use of the radioallergosorbent test (RAST), or a combination of RAST and minor determinant skin testing. Patients with suspected penicillin allergy can undergo desensitization if they require penicillin therapy. The planned return of a commercial major determinant will hopefully resolve this issue.     

Association of IL-10 level and IL-10 promoter SNPs with specific antibodies in penicillin-allergic patients

Objective Our aim was to investigate the hypothesis that the sera interleukin-10 (IL-10) level and polymorphic nucleotides within the IL-10 gene promoters would link to specific IgE and IgG production and the expression of penicillin allergy. Methods One hundred and two patients and 86 healthy subjects were chosen for assay of serum IL-10 level by enzyme-linked immunosorbent assay (ELISA) and type −1082 G/A and −819 C/T alleles by sequence-specific primer polymerase chain reaction (SSP-PCR). Radioallergosorbent test (RAST) and ELISA were used to examine eight types of specific immunoglobulin-E (IgE) and IgG antibodies, respectively, which included four types of antibodies to major and minor antigenic determinants. Results Compared with control subjects and patients with negative-specific IgE, there were significantly lower levels of IL-10 in patients with positive-specific IgE (P < 0.05). Similarly, there were significantly lower levels of IL-10 in patients with positive-specific IgG compared with normal controls and allergic patients with negative-specific IgG (P < 0.05). The visible negative correlations existed between IL-10 and four types of specific IgE [benzylpenicilloyl (BPO), phenoxomethylpenicilloyl (PVO), benzylpenicillanyl (BPA), amoxicillanyl (AXA)], and patients with three or more positive-specific IgE had significantly lower IL-10 levels than normal controls (P < 0.01). There was a declining trend for IL-10 level in serum with the increase in types of positive-specific IgE. But there was no significant difference in serum IL-10 level between the positive skin-test group and the allergic-history group. Compared with controls and patients with negative antibodies, a significantly decreased frequency of the −1082 G allele was present in patients with positive antibodies (P < 0.01). The allele T and TT genotype at −819 C/T position had lower frequency in the negative-specific IgG group than that in the positive group and controls (P < 0.01). Conclusions Positive specific IgE and IgG are associated with decreased IL-10 level in allergic reaction to penicillins. The distributions of genotype and frequency of allele at the −1082 G/A position may be associated with the production of both specific IgE and IgG antibodies.     

青霉素特异性IgE抗体的种类与HLA-DRB基因多态性

目的探讨HLA-DRB基因是否调控青霉素过敏反应产生不同种类的IgE抗体。方法以河南汉族临床青霉素过敏反应的病人为研究对象,采用放射免疫吸附试验(radio allergosorbent test,RAST)检测血清中针对青霉素药物的8种特异性IgE抗体和采用序列特异性引物-聚合酶链反应(pol-ymerase chain reaction sequence-specific primer,PCR-SSP)的方法检测HLA-DRB等位基因。结果80例抗体阳性病人中,BPO、BPA、PVO、PVA、APO、APA、AXO、AXA-IgE阳性的分别为36、33、32、29、21、12、16、33例。与对照组相比,BPO-IgE阳性组DR16基因和PVO阳性组DR14.1基因明显降低(0vs8.62%,P<0.01;1.56%vs9.77%,P<0.05)。结论DR16基因可能与BPO抗原的过敏有关,DR14.1基因可能与PVO抗原的过敏有关。     

Relationships between specific serum IgE,IgG, IFN-γ level and IFN-γ, IFNR1 polymorphisms in patients with penicillin allergy

Objective  The findings of numerous studies have suggested that both genetic and environmental influences are involved in the pathogenesis of allergic disease and atopy. We studied the polymorphisms in the interferon (IFN)-gamma (γ) and IFN-γ receptor 1 (IFNR1) gene with the aim of clarifying the relationships among these polymorphisms, penicillin allergy and anti-penicillin antibodies. Methods  A restriction endonuclease fragment length polymorphism (RFLP)-PCR analysis and sequencing were used to study the IFNR1 and IFN-γ polymorphisms. The presence and level of eight specific immunoglobulin (Ig)E and IgG antibodies were determined by the radioallergosorbent test (RAST) and enzyme-linked immunosorbent assay (ELISA), respectively. Results  The positive rates of specific IgE and IgG were 61.11 and 53.92%, respectively. There was no significant difference in the whole-allele of IFN-γ distribution between patients with a penicillin allergy and control subjects. Allele 7 (18CA repeat) was significantly less frequent in the urticaria group (3.19 vs. 11.93%) than in the controls. There was no difference in IFN-γ production among different alleles in IFN-γ. The frequency of G/A (Val/Met) in the IFNR1 gene in allergic patients was significantly less than that in the controls (P < 0.05). There were no significant differences in the positive rate of IgE among different alleles of IFN-γ. The same was true for the positive rate of IgG. Conclusions  The Met/Val allele in IFNR1 gene may have a protective role in the non-penicillin allergic population. The allele 18CA repeat in IFN-γ gene may be associated with urticaria.     

天津地区食物过敏性患者sIgG检测结果分析

目的 检测过敏患者血清食物过敏原sIgG,探讨食物不耐受与过敏性皮肤病的关系。方法 应用酶联免疫吸附法（ELISA）对834例疑似食物变态反应性疾病患者血清中食物过敏原的sIgG抗体检测,分析食物过敏原种类特点。结果 834例患者中有638例有1～11 种不等的食物过敏原sIgG升高,总阳性率为76.5 %,其中存在1～2 种食物不耐受的比例最高,占58.15 %。在14 种食物中,食物过敏原sIgG升高以蛋清/蛋黄（51.9%）最多见,其次分别是蟹（21.6%）、虾（19.3%）、牛奶（16.5%）, 猪肉（0.5 %）sIgG阳性比率最低。另外,鸡蛋、牛奶、蟹、虾、小麦、西红柿六种食物阳性率存在年龄的差异（P < 0. 01) 。241例皮肤病患者中有171例食物过敏原检测结果呈阳性,阳性反应率为71.0 %。结论 蛋清/蛋黄、甲壳类(蟹、虾) 、牛奶是食物变态反应性疾病的主要过敏原。某些食物在不同年龄中有很高的不耐受率和不耐受程度,可能是食物过敏的主要原因之一。食物过敏或食物不耐受的症状与皮肤过敏性疾病关系密切。     

Immediate hypersensitivity reactions to penicillins and other betalactams

Immediate hypersensitivity reactions to betalactams are IgE mediated and constitute the most frequent allergic reactions mediated by specific immunological mechanisms. IgE responses to benzyl penicillin (BP), the first antibiotic producing the benzyl penicilloyl structure (BPO), are characterized by a quick release of inflammatory mediators, resulting in anaphylactic shock, urticaria and angioedema. With the progressive appearance of other structures, comprising cephalosporins, carbapenems, monobactams and clavulanic acid, IgE selective responses and cross-reactivity reactions were observed. The diagnosis of betalactam hypersensitivity, classically based on skin testing with major and minor determinants of benzyl penicillin or in vitro IgE antibodies to BP, has been modified by the inclusion of different determinants generated from these compounds, for which amoxicillin (AX) is the most relevant, followed by cephalosporins. Some subjects develop positive responses to several betalactams, mostly within the same family, but others develop a selective response. These are relevant for the appropriate selection of antimicrobial drugs in patients who have immediate hypersensitivity to betalactams.     

The prevalence of suspected and challenge-verified penicillin allergy in a university hospital population

Suspected penicillin allergy is common among hospitalised patients, but the quality of the information given by the patient is often doubtful. Alleged penicillin allergic are likely to be treated with more toxic, broad-spectrum, and more expensive antibiotics, with effects on microbial resistance patterns and public economy as a consequence. We performed a cross-sectional case-control study with two visits to all clinical departments of a large university hospital in order to find in-patients with medical files labelled "penicillin allergy" or who reported penicillin allergy upon admission. Patient histories were obtained via a questionnaire, and they were offered investigation for penicillin allergy with specific IgE, basophil histamine release, skin prick tests, intradermal tests and drug challenge tests. Finally, the pharmaco-economical consequences of the penicillin allergy were estimated. In a cohort of 3642 patients, 96 fulfilled the inclusion criteria giving a point-prevalence of alleged penicillin allergy of 5% in a hospital in-patient population. Mean time elapsed since the alleged first reaction to penicillin was 20 years. The skin was the most frequently affected organ (82.2%), maculo-papular exanthema (35.4%) and urticaria (10.4%) being the most frequently reported reactions. 25% did not recall the time of their reaction. 82.2% did not remember the name of the penicillin they reacted to. 34.8% had been treated with penicillins after suspicion of penicillin allergy had been raised. None of these reacted to penicillins. 33.3% of the patients receiving antibiotics during their current hospitalisation were prescribed penicillins. 2% developed non-severe exanthema. The average acquisition costs for antibiotics to penicillin allergic patients were euro 278, compared to euro 119 had they been non-allergic. The prevalence of suspected penicillin allergy was lower than reported elsewhere. A substantial number of patients failed to recall basic information about their alleged allergy. Patients reporting penicillin allergy upon admission and labels stating penicillin allergy on medical files are ignored in almost a third of patients receiving antibiotics. The acquisition costs for antibiotics to penicillin allergic patients were higher, compared to the cost had the patients been non-allergic.     

Clinical importance of carbapenem hypersensitivity in patients with self-reported and documented penicillin allergy

The risk of carbapenem hypersensitivity in patients with self-reported or documented penicillin allergy needs to be determined so that practitioners can make better-informed decisions regarding antibiotic therapy for this patient population. The risk of cross-reactivity between penicillin and carbapenem antibiotics initially was reported to approach 50%. Recent retrospective studies have suggested that the clinical risk of cross-hypersensitivity between these two drug classes is 9.2-11%, which is significantly lower than initially reported. Patients whose history of penicillin allergy is self-reported and is not type 1 may be at moderate risk for hypersensitivity when treated with a carbapenem antibiotic. The risk of hypersensitivity appears to be higher in patients whose penicillin allergy was documented by a health care provider, those with several antibiotic allergies, and those with a positive penicillin skin test result or a history of type 1 penicillin hypersensitivity.