Cephalosporin and penicillin cross-reactivity in patients allergic to penicillins.

BACKGROUND: Bata-lactam antibiotics are the most commonly used antibiotics which usually cause serious IgE-mediated allergic reactions. Of all bata-lactam antibiotics, penicillins have so far been the best-studied, but the studies of cephalosporins and their cross-reactivity with penicillins are rare. We sought to evaluate the IgE response in vitro and estimate cross-reactivity between penicillins and cephalosporins in patients allergic to penicillins. METHODS: We studied 87 control subjects and 420 subjects allergic to penicillins. Radioallergosorbent test (RAST) was performed to detect eight types of specific-penicillin IgE and eleven types of specific-cephalosporin IgE. The cross-reactivity and different molecules recognition by IgE were studied with a radioallergosorbent inhibition test. RESULTS: Of 420 patients allergic to penicillins, 95 patients (22.62%) showed specific-cephalosporin IgE positive, 73 patients (17.38%) showed IgEs positive to both penicillins and cephalosporins. In specific-penicillin IgE positive group, the positive rate of specific-cephalosporin IgE was significantly higher than in specific-penicillin IgE negative group (27.14% vs. 14.57%, p < 0.01). In urticaria group, the positive rate of specific-cephalosporin IgE was significantly higher than in other symptoms group (30.65% vs. 8.11%, p < 0.05). The analysis of drugs which have the same or similar side-chains showed that benzylpenicillanyl-IgE (BPA-IgE), ampicillanyl-IgE (APA-IgE), amoxicillanyl-IgE (AXA-IgE) were respectively related to cephalothanyl-IgE (CLA-IgE), cephalexanyl-IgE (CEXA-IgE), cephalexanyl-IgE (CEXA-IgE)in sera of penicillin-allergic patients we studied, and compared with patients who had negative amoxicillin-IgE, the positive rates of specific-ampicillin IgE and specific-cephalexin IgE were significantly higher in patients who had positive amoxicillin-IgE (14.43% vs. 3.72%, 14.00% vs. 2.96%, p < 0.01). Radioallergosorbent test and radioallergosorbent inhibition test confirmed that both nuclear structure and R1 side-chain contribute to IgE recognition. CONCLUSIONS: There exists cross-reactivity between cephalosporins and penicillins; patients allergic to several penicillins are more likely to develop allergic reaction to cephalosporins; due to sensitization to the similar structural characteristics (nuclear and R1 side-chain), penicillin-allergic patients may develop cross-allergic reactions with not only first-generation but also third-generation cephalosporins.

Hypersensitivity reactions to penicillins: studies in a group of patients with negative benzylpenicillin G skin test.

BACKGROUND: Although skin tests are usually employed to evaluate current penicillin allergy status, a negative result does not exclude hypersensitivity. There is a need for accurate in vitro tests to exclude hypersensitivity. A radioallergosorbent test (RAST) is a potentially good supplementary approach, but there is little information on the suitability of this method to diagnose penicillin hypersensitivity in subjects with a negative skin test to benzylpenicillin. METHODS: A total of 133 patients with a negative skin test to benzylpenicillin G (PG) and all of whom developed allergic reactions to PG were studied. RAST was used to detect eight kinds of specific IgE antibodies to penicillins in serum, which included four kinds of major and minor antigenic determinants to four penicillin drugs. The combination sites for the specific IgE antibodies were studied by RAST inhibition test. RESULTS: The rate of positive reactions for the specific IgE antibodies was 59.40% (79/133). Of the eight kinds of antigenic determinants, the positive rates for specific IgE against the major and minor determinants were 39.10% (52) and 42.86% (57) respectively. Of the four drugs, positive cases only to PG were 10 (7.5%), were significantly fewer than the cross-reacting positive cases (36) to PG (P < 0.01). In the RAST inhibition studies all drugs exhibited good inhibitory potencies, and in some instances the side-chain of the penicillins could induce specific responses with a variable degree of cross-reactivity among the different penicillins. CONCLUSION: Radioallergosorbent test is a good complementary test in persons who are skin-test negative with PG, and the sensitivity of RAST increases with increasing specificity of IgE antibodies to be detected. 6-APA and the groups, making part of the different side-chains on penicillins, all contributed to the cross-reactivity.

Interleukin-18 and IL18 -607A/C and -137G/C gene polymorphisms in patients with penicillin allergy.

This study investigated the association between polymorphisms (-607A/C and -137G/C) in the promoter region of the IL18 gene (which encodes interleukin [IL]-18) and serum levels of IL-18, using standard genotyping techniques (sequence specific primer-polymerase chain reaction) and an enzyme-linked immunosorbent assay, respectively, in patients allergic to penicillin. A higher frequency of A alleles and the AA genotype was found at position -607A/C in patients allergic to penicillin than in control subjects. For the -137G/C position, the C allele was more frequent in patients allergic to penicillin than in control subjects. Haplotype analysis showed that the -607A/-137C haplotype was more frequent in patients allergic to penicillin than in control subjects. The patients had a significantly higher serum IL-18 level than the control subjects. In conclusion, IL18 -607A/C and -137G/C promoter polymorphisms are associated with susceptibility to penicillin allergy. In particular, the -137G/C position appears to play an important role in IL18 expression.

Relationships between specific serum IgE, cytokines and polymorphisms in the IL-4, IL-4Ralpha in patients with penicillins allergy.

BACKGROUND: Excessive production of interleukin (IL)-4, IL-13 and interferon (IFN)-gamma is thought to be important in the development of allergic disease and atopy. Several investigators have linked the IL-4 and IL-4R genes to allergic disease and atopy. The aim of this study is to further explore the mechanism of penicillins allergy and evaluate the possible role of the IL-4 C-589T and IL-4RalphaQ576R polymorphisms in modulating the allergic responses to penicillins. METHODS: Radioallergosorbent test (RAST) was used to detect eight kinds of specific immunoglobulin E (IgE) to penicillins in serum. Serum levels of IL-4, IL-13 and IFN-gamma were measured by using enzyme-linked immunosorbent assay (ELISA). The IL-4 C-589T and IL-4RalphaQ576R polymorphisms were genotyped by polymerase chain reaction restriction fragment length polymorphism (PCR-RFLP). RESULTS: Compared with control subjects, there were significantly higher levels of IL-4, IL-13 and IFN-gamma in allergic patients with positive specific IgE (P < 0.01), and the lower levels of IL-4 and IFN-gamma were observed in allergic patients with negative specific IgE (P < 0.05). We found a growing trend of IL-4 and IL-13 levels with the kind increasing of positive specific IgE, and even there were significant correlations between the three kinds of cytokines and many kinds of specific IgE (P < 0.05). The IL-4Ralpha*Q576 allele was significantly increased in patients with penicillins allergy compared with control subjects (P < 0.01). Furthermore, the allele was strongly associated with increased serum-specific benzylpenicilloyl (BPO)-, phenoxomethylpenicillanyl (PVA)- or ampicillanyl (APA)-IgE levels in patients with positive specific IgE (P < 0.05). CONCLUSIONS: These data suggest that IL-4, IL-13 and IFN-gamma play an important roles in penicillins allergy. The IL-4RalphaQ576R polymorphism may involve in the development of penicillins allergy, and through modulating specific serum IgE levels.

Relationships between skin test, specific IgE and levels of cytokines in patients with penicillin allergy.

The aim of this study was to investigate the relationships between skin test, specific immunoglobulin (Ig) E and cytokines in penicillin allergy. We collected the sera of 259 patients with historical positive skin test to penicillins, with immediate positive skin test and with a negative skin test results. The positive rate of specific IgE antibodies in 259 patients was 62.2% (161) by using radioallergosorbent test (RAST). Of the eight kinds of antigenic determinants, the positive rates of specific IgE to major and minor determinants were 43.63% (113) and 52.51% (136), respectively (p < 0.05). In 122 patients with immediate positive skin test, when the degrees of skin test were +, 2+, 3+ and 4+, the positive rates of specific IgE were 45.7, 57.1, 85.2 and 100%, respectively. The levels of interleukin (IL)-4, IL-13 and interferon (IFN)-gamma in the sera of patients with positive skin test were significantly increased with the degree of positive skin test (p < 0.05). The combined use of major and minor determinants in RAST offers the better test for the detection of penicillin-specific IgE antibodies. IL-4, IL-13 and IFN-gamma play important roles in penicillin allergy.

Specific serum IgE levels and FcepsilonRIbeta genetic polymorphism in patients with penicillins allergy.

BACKGROUND: Numerous studies have suggested that both genetic and environmental influences are involved in the pathogenesis of allergic disease and atopy. The objective of this investigation is to elucidate the underlying mechanism of penicillins allergy and improve the diagnostic methods. METHODS: Radioallergosorbent test was used to examine eight kinds of specific IgE antibodies, which included four kinds of major and minor antigenic determinants, respectively, in the sera of 448 patients with penicillins allergy and 101 healthy subjects. A restriction endonuclease fragment length polymorphism of a polymerase chain reaction product was used for analysis of the FcepsilonRIbeta polymorphism. RESULTS: The positive rate of specific IgE in 448 patients was 58.26% (261), in which 37.28% (167) patients had positive IgE to major antigenic determinants and 47.09% (211) patients had positive IgE to minor antigenic determinants. Of the 179 patients with allergic history, 70.83% (17/24) patients had positive antibodies within 30 days, while 45.28% (24/53) had positive antibodies after 5 years. The positive reaction degree of skin test was absolutely correlated with specific IgE (P=0.047). Among patients with positive specific IgE, significant differences of E237G genotype were observed between patients with positive benzylpenicillanyl (BPA)-, phenoxomethylpenicilloyl (PVO)- or ampicilloyl (APO)-IgE and control group (P=0.015, 0.015, and 0.008, respectively). There were significant differences in E237G genotype between positive and negative BPA-, PVO- as well as APO-IgE patients (P = 0.014, 0.02, and 0.011, respectively). CONCLUSIONS: The patients with penicillins allergy have positive specific IgE not only to major antigenic determinants but also to minor antigenic determinants. The E237G variant of the FcepsilonRIbeta gene is involved in the development of penicillins allergy through the process for the production of specific IgE antibodies.