Background Because of the pivotal role of the human leukocyte antigen (HLA) class II molecules in regulating the immune response and their extensive polymorphism, it is not surprising that particular HLA class II al...Background Because of the pivotal role of the human leukocyte antigen (HLA) class II molecules in regulating the immune response and their extensive polymorphism, it is not surprising that particular HLA class II alleles have been implicated in susceptibility to allergic diseases and in restriction of the IgE responses to a variety of allergens. We investigated the relationship between HLA-DRB genotype and allergies to various penicillins and explored HLA-DRB restriction of IgE responses to these derivatives of penicillin.Methods Radioallergosorbent test was used to examine 8 kinds of specific IgE antibodies (4 major and 4 minor antigenic determinants) in the sera of 248 patients with an allergy to penicillins and 101 healthy subjects without any allergic reaction. Some (113 patients and 87 healthy control subjects) were chosen from all subjects to type for HLA-DRB alleles by sequence specific primer-polymerase chain reaction.Results Compared with control subjects, a sign/ficantly increased frequency of DR9 was present in 77 patients with allergic reactions, with immediate hypersensitive reaction and with urticaria (P = 0.011; P = 0.019; P = 0.005 respectively). Conversely, a significantly decreased frequency of DR14.1 was found in 80 patients with positive IgE antibodies, with immediate reaction and with urticaria compared with control group (P = 0.024; P = 0.038; P = 0.038). A possible excess of HLA-DR17 was found in subjects who were responsive to benzylpenicilloyl compared with those were not (X^2 = 5.134, P = 0.023), and of HLA-DR4 was found in subjects responsive to phenoxomethylpenicillanyl (PVA, X^2 = 4.057, P = 0.044).Conclusion I-ILA-DRB gene may be involved in allergy to pcnicillins through modulating spvcific serum IgE to penicillins.展开更多
Objective. Atopic asthma provides a useful model for evaluating the genetic factors that control human immune responsiveness. HLA class Ⅱ gene products are involved in the control of immune response. As HLA-DRB gene ...Objective. Atopic asthma provides a useful model for evaluating the genetic factors that control human immune responsiveness. HLA class Ⅱ gene products are involved in the control of immune response. As HLA-DRB gene is the most polymorphic HLA class Ⅱ gene, we investigated whether susceptibility or resistance to the disease is associated with HLA-DRB. Methods. Blood samples were obtained from two groups of unrelated Chinese northern adults: (l) 50 atopic asthma (7 of them with familial aggregation) ;(2) 80 healthy controls without asthma or atopy and other HLA-associated diseases. Genomic DNA was extracted from peripheral venous blood leucocytes. The polymorphic second exon of HLA-DRB gene was amplified by sequence-specific primer polymerase chain reaction (SSP/PCR) methods. All patients had their serum IgE (total and specific) antibody levels by RAST, bronchial reactivity assessed by methacholine brocho-provocation test and/or bronchodilation test. Results. There was an increased gene frequency of DR6(13) and DR52 in asthmatic subjects compared with healthy subjects(17% vs 4. 3%, P<0.01; 50% vs 17. 5 %, P<0. 01 ), and the decreased frequency of DR2(15) and DR51 in asthmatic patients(7% vs 18%, P<0. 05; 2 % vs 33 %, P<0. 01 ). We found the positive association between DR6(13)-DR52 and sIgE antibody responsiveness to dl (from house dust mite al- lergen ); negative association between HLA-DRB alleles and TIgE or BHR (bronchial hyperresponsiveness ). Conclusion. The results suggested that HLA haplotype DR6(13)-DR52 was significantly implicated in sus- ceptibility to house dust mite induced-asthma, at least it would be more closely associated with atopic asth- ma. Conversely, alleles DR2(15) and DR51 might confer protection against the disease. HLA-DRB genes were particularly involved in regulating human atopic immune response in asthma.展开更多
基金This study was supported by grants from the Science Foundation for Distinguished Young Scholars of Henan Province (No. 0312002100)the Nature Science Foundation of Henan Province (No. 0211040100).
文摘Background Because of the pivotal role of the human leukocyte antigen (HLA) class II molecules in regulating the immune response and their extensive polymorphism, it is not surprising that particular HLA class II alleles have been implicated in susceptibility to allergic diseases and in restriction of the IgE responses to a variety of allergens. We investigated the relationship between HLA-DRB genotype and allergies to various penicillins and explored HLA-DRB restriction of IgE responses to these derivatives of penicillin.Methods Radioallergosorbent test was used to examine 8 kinds of specific IgE antibodies (4 major and 4 minor antigenic determinants) in the sera of 248 patients with an allergy to penicillins and 101 healthy subjects without any allergic reaction. Some (113 patients and 87 healthy control subjects) were chosen from all subjects to type for HLA-DRB alleles by sequence specific primer-polymerase chain reaction.Results Compared with control subjects, a sign/ficantly increased frequency of DR9 was present in 77 patients with allergic reactions, with immediate hypersensitive reaction and with urticaria (P = 0.011; P = 0.019; P = 0.005 respectively). Conversely, a significantly decreased frequency of DR14.1 was found in 80 patients with positive IgE antibodies, with immediate reaction and with urticaria compared with control group (P = 0.024; P = 0.038; P = 0.038). A possible excess of HLA-DR17 was found in subjects who were responsive to benzylpenicilloyl compared with those were not (X^2 = 5.134, P = 0.023), and of HLA-DR4 was found in subjects responsive to phenoxomethylpenicillanyl (PVA, X^2 = 4.057, P = 0.044).Conclusion I-ILA-DRB gene may be involved in allergy to pcnicillins through modulating spvcific serum IgE to penicillins.
基金State Science and Technology Commission of China !(No. 96-906-02-04)Glaxowellcome Ltd.
文摘Objective. Atopic asthma provides a useful model for evaluating the genetic factors that control human immune responsiveness. HLA class Ⅱ gene products are involved in the control of immune response. As HLA-DRB gene is the most polymorphic HLA class Ⅱ gene, we investigated whether susceptibility or resistance to the disease is associated with HLA-DRB. Methods. Blood samples were obtained from two groups of unrelated Chinese northern adults: (l) 50 atopic asthma (7 of them with familial aggregation) ;(2) 80 healthy controls without asthma or atopy and other HLA-associated diseases. Genomic DNA was extracted from peripheral venous blood leucocytes. The polymorphic second exon of HLA-DRB gene was amplified by sequence-specific primer polymerase chain reaction (SSP/PCR) methods. All patients had their serum IgE (total and specific) antibody levels by RAST, bronchial reactivity assessed by methacholine brocho-provocation test and/or bronchodilation test. Results. There was an increased gene frequency of DR6(13) and DR52 in asthmatic subjects compared with healthy subjects(17% vs 4. 3%, P<0.01; 50% vs 17. 5 %, P<0. 01 ), and the decreased frequency of DR2(15) and DR51 in asthmatic patients(7% vs 18%, P<0. 05; 2 % vs 33 %, P<0. 01 ). We found the positive association between DR6(13)-DR52 and sIgE antibody responsiveness to dl (from house dust mite al- lergen ); negative association between HLA-DRB alleles and TIgE or BHR (bronchial hyperresponsiveness ). Conclusion. The results suggested that HLA haplotype DR6(13)-DR52 was significantly implicated in sus- ceptibility to house dust mite induced-asthma, at least it would be more closely associated with atopic asth- ma. Conversely, alleles DR2(15) and DR51 might confer protection against the disease. HLA-DRB genes were particularly involved in regulating human atopic immune response in asthma.