The Experts below are selected from a list of 327 Experts worldwide ranked by ideXlab platform

Simon Mallal - One of the best experts on this subject based on the ideXlab platform.

  • a sensitive and rapid alternative to hla typing as a genetic screening test for abacavir hypersensitivity syndrome
    Pharmacogenetics and Genomics, 2006
    Co-Authors: A Martin, Romano Krueger, David Nolan, Coral Ann Almeida, Elizabeth J Phillips, Simon Mallal
    Abstract:

    Background: Abacavir hypersensitivity reaction (ABC HSR) is a potentially life-threatening adverse reaction that affects approximately 8% of patients that initiate this antiretroviral drug. Independent groups have shown a strong predictive association between ABC HSR and HLA-B*5701, indicating that exclusion of HLA-B*5701 positive individuals from abacavir treatment would largely prevent ABC HSR. However, the limited availability and relatively high cost of human leukocyte antigen (HLA) typing represent barriers to the widespread implementation of this pharmacogenetic approach to abacavir prescribing. To facilitate routine screening, we have developed a rapid flow cytometry method for HLA-B57 phenotyping using commercially available B17 monoclonal antibodies. Methods: Whole blood samples from 84 human immunodeficiency virus (HIV)+ patients were examined by standard flow cytometry methods, using a two-colour B17-specific immunofluorescence assay in the CD45+ lymphocyte population. Results: All eight HLA-B57 individuals examined tested positive, while HLA-B57/58 negative individuals (n=74) tested negative for this flow cytometry test. Two non-HLA-B57 individuals showed weak cross-reactivity. Conclusion: In our predominantly Caucasian population, B17/CD45 dual staining was sufficient to identify individuals carrying B17 cell surface antigens. This approach, utilizing flow cytometry methods that are widely available in HIV laboratories, therefore offers a sensitive, rapid and cost-effective screening assay prior to abacavir prescription. Following risk stratification with this assay, it would be anticipated that identification of HLA-B*5701 using molecular HLA typing methods would be required in <10% of the screened population.

  • A sensitive and rapid alternative to HLA typing as a genetic screening test for abacavir hypersensitivity syndrome
    Pharmacogenetics and Genomics, 2006
    Co-Authors: Annalise M. Martin, Romano Krueger, Elizabeth Phillips, David Nolan, Coral Ann Almeida, Simon Mallal
    Abstract:

    BACKGROUND: Abacavir hypersensitivity reaction (ABC HSR) is a potentially life-threatening adverse reaction that affects approximately 8% of patients that initiate this antiretroviral drug. Independent groups have shown a strong predictive association between ABC HSR and HLA-B*5701, indicating that exclusion of HLA-B*5701 positive individuals from abacavir treatment would largely prevent ABC HSR. However, the limited availability and relatively high cost of human leukocyte antigen (HLA) typing represent barriers to the widespread implementation of this pharmacogenetic approach to abacavir prescribing. To facilitate routine screening, we have developed a rapid flow cytometry method for HLA-B57 phenotyping using commercially available B17 monoclonal antibodies. METHODS: Whole blood samples from 84 human immunodeficiency virus (HIV) patients were examined by standard flow cytometry methods, using a two-colour B17-specific immunofluorescence assay in the CD45 lymphocyte population. RESULTS: All eight HLA-B57 individuals examined tested positive, while HLA-B57/58 negative individuals (n=74) tested negative for this flow cytometry test. Two non-HLA-B57 individuals showed weak cross-reactivity. CONCLUSION: In our predominantly Caucasian population, B17/CD45 dual staining was sufficient to identify individuals carrying B17 cell surface antigens. This approach, utilizing flow cytometry methods that are widely available in HIV laboratories, therefore offers a sensitive, rapid and cost-effective screening assay prior to abacavir prescription. Following risk stratification with this assay, it would be anticipated that identification of HLA-B*5701 using molecular HLA typing methods would be required in

Nobuhisa Mizuki - One of the best experts on this subject based on the ideXlab platform.

  • HLA-B51 Carriers are Susceptible to Ocular Symptoms of Behçet Disease and the Association between the Two Becomes Stronger towards the East along the Silk Road: A Literature Survey
    Ocular Immunology and Inflammation, 2016
    Co-Authors: Yukihiro Horie, Nobuhisa Mizuki, Akira Meguro, Tohru Ohta, Kenichi Namba, Kazuomi Mizuuchi, Daiju Iwata, Hidetoshi Inoko
    Abstract:

    ABSTRACTPurpose: Behcet disease (BD) is predominantly found between East Asia and the Mediterranean basin along the historic Silk Road. HLA-B51 is known to be strongly associated with BD. We investigated the association between HLA-B51 and the ocular manifestations of BD among various ethnic groups.Methods: A literature survey was conducted, and 18 articles written in English were reviewed.Results: A strong correlation was found between HLA-B51 and ocular lesions in the entire cohort discussed in the reviewed articles (OR = 1.76, p = 0.000057). HLA-B51 was shown to have a strong association with ocular manifestations of BD patients in East-Eurasian (OR = 2.40, p = 0.0030) and Middle-Eurasian (OR = 1.87, p = 0.0045), but not in West-Eurasian (OR = 1.28, p = 0.35) areas. This correlation seemed to become stronger towards the east.Conclusions: A meta-analysis showed that the correlation became stronger towards the east along the Silk Road. The study results may facilitate understanding of the etiology and ch...

  • Single nucleotide polymorphisms of Ficolin 2 gene in Behçet's disease
    Journal of Dermatological Science, 2006
    Co-Authors: Xixue Chen, Yasunobu Katoh, Koichiro Nakamura, Noritaka Oyama, Fumio Kaneko, Yuichi Endo, Teizo Fujita, Tomomi Nishida, Nobuhisa Mizuki
    Abstract:

    Summary Background Genetic susceptibility to Behcet's disease (BD) is well documented for HLA-B51 positivity. However, BD is not a simple hereditary disease and it is exaggerated by exogenous stimuli such as microorganisms’ infections. Ficolin 2 is a lectin that binds to the surface of microbial cells and kills microbial cells through the activation of complement system. Novel single nucleotide polymorphisms (SNPs) of human Ficolin 2 gene (FCN2 gene) have been recently identified in Caucasian people. Objective The aim of the study was to elucidate the contribution of FCN2 gene in the pathogenesis of BD. Methods The frequencies of genotypes and alleles of FCN2 gene SNPs in the promoter regions (−987, −602, −557, −64, −4) and exon 8 (+6359, +6424) were examined in 83 patients with BD and 64 healthy controls by genotyping with a DNA sequencing method. Results There were no significant differences in genotype and allele frequencies of FCN2 gene SNPs between BD patients and healthy controls. No significant differences in genotype and allele frequencies of FCN2 gene SNPs were detected among different clinical subgroups in BD patients. Significant differences in allele frequencies of FCN gene SNPs at both −557 and −64 sites in the promoter regions were found between HLA-B51 positive groups and HLA-B51 negative groups of BD patients. Conclusion The significant differences in allele frequencies of FCN2 gene SNPs in the promoter lesions (−557 and −64 sites) among HLA-B51 positive BD patients may reveal the possibility that ficolin may contribute to the innate immunity of BD among HLA-B51 haplotypes in BD patients.

  • Analysis of microsatellite polymorphism around the HLA‐B locus in Iranian patients with Behçet's disease
    Tissue Antigens, 2002
    Co-Authors: Nobuhisa Mizuki, H. Ando, Fereydoun Davatchi, Kazuro Yabuki, Yoshihiko Katsuyama, Eiichi Nomura, K. Funakoshi, H. Chams, Behrooz Nikbin
    Abstract:

    : We have previously suggested that in a Japanese population the susceptible locus for Behcet's disease (BD) is HLA-B51 itself. To confirm this finding in another population, we performed HLA class I typing using the PCR-SSP method and analyzed eight polymorphic markers distributed within 1100 kb around the HLA-B gene using automated sequencer and subsequent automated fragment detection by fluorescent-based technology with the DNA samples of 84 Iranian patients with BD and 87 healthy ethnically matched controls. As a result, three microsatellite alleles (MICA-A6, MIB-348, C1-4-1-217) and HLA-B51 were found to be strongly associated with BD. Of these alleles HLA-B51 is the most strongly associated allele. There were no alleles that were increased in allele frequency at any microsatellite loci centromeric of MICA or telomeric of HLA-B51. Therefore, HLA-B51 was confirmed to be by far the most strongly associated gene with BD in an Iranian population.

  • The absence of disease-specific polymorphisms within the HLA-B51 gene that is the susceptible locus for Behcet's disease
    Tissue Antigens, 2001
    Co-Authors: Kazumi Sano, Nobuhisa Mizuki, Shigeaki Ohno, Kazuro Yabuki, Y. Imagawa, Takashi Shiina, Jerzy K. Kulski, Hidetoshi Inoko
    Abstract:

    Behcet's disease is known to be associated with HLA-B51 in many different populations. Genetic evidence supports that the susceptible gene for Behcet's disease is the HLA-B51 allele at the HLA-B locus. This study was aimed to determine the HLA-B51 nucleotide sequence variation in three Behcet's disease patients and three healthy controls in order to elucidate if any disease specific mutations or polymorphisms may exist in the HLA-B51 gene of patients. Long-range polymerase chain reaction (PCR) was first carried out to give a PCR-amplified product of 9.5 kb which was then used as a template for nested PCR to give a final amplified product of 4.2 kb. This final product containing the 1.3-kb promoter/enhancer region and the entire HLA-B gene except for a 363-bp 3′ terminal end segment encoding the 3′ untranslated region was subcloned by the BP cloning technique and sequenced. The sequencing results showed that all the patients possessed the HLA-B*51011 allele, and there were no differences in the exonic nucleotide sequences between the three Behcet's disease patients and the three healthy controls. The HLA-B*51011 intronic and promoter/enhancer nucleotide sequences from the three patients had 22 single nucleotide polymorphisms (SNPs), a single insertion of 6 bp and a single deletion of 2 bp. On the other hand, the three healthy controls had 24 SNPs in their intronic and promoter/enhancer regions. However, none of these polymorphisms in the patients were specific for the disease. Therefore, these results clearly demonstrate that the HLA-B exonic sequence that encodes the HLA-B51 allele is the real pathogenic factor in Behcet's disease.

  • Microsatellite mapping of a susceptible locus within the HLA region for Behçet's disease using Jordanian patients.
    Human Immunology, 2001
    Co-Authors: Nobuhisa Mizuki, H. Ando, Kazuro Yabuki, Yoshihiko Katsuyama, David Verity, Katsuhiro Onari, Kaori Goto, Yukari Imagawa, Wafa Mandanat
    Abstract:

    Abstract Behcet’s disease (BD) has been established to be associated with HLA-B51. However, it has not been revealed whether the HLA-B51 gene itself or another gene located near the HLA-B gene is directly involved in the pathogenesis of BD. Previously, using Japanese BD patients, our group has narrowed down a BD-causative gene to 46 kb between the MICA and HLA-B genes by means of fine mapping analysis with eight microsatellite markers distributed within a 1100 kb segment around the HLA-B gene. To know whether this mapping result is generally observed in BD of another population we have investigated repeat polymorphisms of the same microsatellite markers in Jordanian BD patients. Furthermore, we have evaluated these data by Mantel-Haenzel stratified analysis to find out a primarily associated locus for BD. As a result, HLA-B51 was found to be the most strongly and primarily associated marker. This result suggests that the pathogenic gene of BD is HLA-B51 itself, but unlikely to be other genes located in the vicinity of HLA-B.

Masafumi Takiguchi - One of the best experts on this subject based on the ideXlab platform.

  • Binding of nonamer peptides to three HLA-B51 molecules which differ by a single amino acid substitution in the A-pocket
    Immunogenetics, 1996
    Co-Authors: Akiko Kikuchi, Takashi Sakaguchi, Kiyoshi Miwa, Yuji Takamiya, Hans-georg Rammensee, Yutaro Kaneko, Masafumi Takiguchi
    Abstract:

    The interaction between 9-mer peptides and HLA-B51 molecules was investigated by quantitative peptide binding assay using RMA-S cell expressing human β2-microglobulin and HLA-B51 molecules. Of 147 chemically synthesized 9-mer peptides possessing two anchor residues corresponding to the motif of HLA-B^*5101 binding self-peptides, 27 paptides bound to HLA-B^*5101 molecules. Pro and Ala at position 2 as well as Ile at position 9 were confirmed to be main anchor residues, while Gly at position 2 as well as Val, Leu, and Met at position 9 were weak anchor residues for HLA-B^*5101. The A-pocket is suspected to have a critical role in peptide binding to MHC class I molecules because this pocket corresponds to the N-terminus of peptides and has a strong hydrogen bond formed by conserved Tyr residues. Further analysis of peptide binding to HLA-B^*5102 and B^*5103 molecules showed that a single amino acid substitution of Tyor for His at residue 171(B^*5102) and that of Gly for Trp at residue 167 (B^*5103) has a minimum effect in HLA-B51-peptide binding. Since previous studies showed that some HLA-B51 alloreactive CTL clones failed to kill the cells expressing HLA-B^*5102 or HLA-B^*5103, these results imply that the structural change of the A-pocket among HLA-B51 subtypes causes a critical conformational change of the epitope for TCR recognition rather than influences the interaction between peptides and MHC class I molecules.

  • Isolation of a human allo-peptide presented by HLA-B51 molecules
    International Immunology, 1995
    Co-Authors: Hiroko Tomiyama, Yuji Takamiya, Ann B. Hill, Vincenzo Cerundolo, Adrian Kelly, Kohji Egawa, John Trowsdale, Masafumi Takiguchi
    Abstract:

    Recent studies have demonstrated directly that alloreactive mouse CTL recognize peptides presented by MHC class I molecules. However, there is no direct evidence that human alloreactive CTL recognize peptides presented by HLA class I molecules. We have isolated an HLA-B51 alloreactive CTL clone, 2B3, that did not kill the TAP defective cell lines T2 and .174, whereas it killed the TAP-positive cell line T1 and .174 cells transfected with TAP genes. These findings suggested that this clone recognizes a TAP-dependent allo-peptide. We attempted to isolate the human allo-peptide recognized by the 2B3 clone from HLA-B51 molecules. A naturally occurring HLA-B*5101 binding peptide isolated from T1 cells was recognized by the 2B3 clone. The peptide was also isolated from HLA-B*5101 molecules purified from C1R-B*5101 cells. In the present study, we directly demonstrated that a human alloreactive CTL clone recognizes peptide presented by HLA class I molecules.

  • Excessive function of peripheral blood neutrophils from patients with behcet's disease and from hla‐b51 transgenic mice
    Arthritis & Rheumatism, 1995
    Co-Authors: Mitsuhiro Takeno, Masafumi Takiguchi, Ai Kariyone, N. Yamashita, Yutaka Mizushima, Hidetoshi Kaneoka, Tsuyoshi Sakane
    Abstract:

    Objective. To elucidate the role played by HLA-B51 in the neutrophil hyperfunction of Behcet's disease, we determined the superoxide production by purified peripheral blood neutrophils from Behcet's disease patients, from HLA-B51 positive healthy individuals, and from HLA-B51 transgenic mice. Methods. Neutrophil function was evaluated by flow cytometric analysis, detecting the conversion of 2′,7′-dichlorofluorescin diacetate into dichlorofluorescein, induced by superoxide in the neutrophils. Results. A significant correlation between the neutrophil hyperfunction and the possession of HLA-B51 phenotype, regardless of the presence of the disease, was observed in humans. FMLP-stimulated neutrophils (without in vitro priming) from HLA-B51 transgenic mice, but not those from HLA-B35 transgenic mice or from nontransgenic mice, produced substantial amounts of superoxide. Conclusion. The HLA-B51 molecule itself may be responsible, at least in part, for neutrophil hyper-function in Behcst's disease.

  • Behcet's Disease Associated With one of the HLA-B51 Subantigens, HLA-B* 5101
    American Journal of Ophthalmology, 1993
    Co-Authors: Nobuhisa Mizuki, Masafumi Takiguchi, Hidetoshi Inoko, H. Ando, Satoshi Nakamura, Kouichi Kashiwase, Tatsuya Akaza, Yujiro Fujino, Kanjiro Masuda, Shigeaki Ohno
    Abstract:

    The strong association of Behcet's disease with HLA-B51 in several ethnic groups is well known. Because the HLA-B51 antigen has been recently identified to comprise three alleles, HLA-B * 5101, HLA-B * 5102, and HLA-B * 5103, we sought to investigate whether there is any correlation of one particular allele among them with B51-positive patients with Behcet's disease. Forty-six Japanese patients with Behcet's disease and HLA-B51 were typed by using the alloantisera, which allowed the subdivision of B51 antigen by the microlymphocyte toxicity assay. All the patients were found to carry HLA-B * 5101. This result suggests that amino acid substitutions at residue 167 or 171 prevent the development of Behcet's disease, because HLA-B * 5101 differs from HLA-B * 5102 and HLA-B * 5103 by single amino acid substitution at residues 171 and 167, respectively, or that another non-HLA gene tightly linked to the HLA-B * 5101-associated haplotype around the HLA class I gene region is responsible for the susceptibility to Behcet's disease. This study provides insight into the molecular mechanism underlying an HLA association with Behcet's disease.

  • Different rates of HLA class I molecule assembly which are determined by amino acid sequence in the α2 domain
    Immunogenetics, 1993
    Co-Authors: Ann Hill, Masafumi Takiguchi, Andrew Mcmichael
    Abstract:

    Assembly of HLA class I molecules was studied using pulse-chase labeling of B-lymphoblastoid cell lines with ^35S-methionine, immunoprecipitation with antibodies detecting free or β_2-microglobulin-associated heavy chain and isoelectric focusing. Marked differences between the products of different class I alleles were noted. HLA-B51 assembled very inefficiently, with considerable free heavy chain still detected in an unsialated form after a four hour chase. The closely related molecule HLA-B35 was in contrast rapidly assembled, all newly synthesized heavy chain being detected in a β2m-associated, sialated form within 30 minutes. Analysis of naturally occurring variants related to HLA-B35 and HLA-B51 localized the region determining assembly efficency to the α2 domain, in which these molecules differ at eight amino acid residues. The effect was not due to a linked dominant gene, as both patterns of assembly were observed in a single cell line.

Shigeaki Ohno - One of the best experts on this subject based on the ideXlab platform.

  • The absence of disease-specific polymorphisms within the HLA-B51 gene that is the susceptible locus for Behcet's disease
    Tissue Antigens, 2001
    Co-Authors: Kazumi Sano, Nobuhisa Mizuki, Shigeaki Ohno, Kazuro Yabuki, Y. Imagawa, Takashi Shiina, Jerzy K. Kulski, Hidetoshi Inoko
    Abstract:

    Behcet's disease is known to be associated with HLA-B51 in many different populations. Genetic evidence supports that the susceptible gene for Behcet's disease is the HLA-B51 allele at the HLA-B locus. This study was aimed to determine the HLA-B51 nucleotide sequence variation in three Behcet's disease patients and three healthy controls in order to elucidate if any disease specific mutations or polymorphisms may exist in the HLA-B51 gene of patients. Long-range polymerase chain reaction (PCR) was first carried out to give a PCR-amplified product of 9.5 kb which was then used as a template for nested PCR to give a final amplified product of 4.2 kb. This final product containing the 1.3-kb promoter/enhancer region and the entire HLA-B gene except for a 363-bp 3′ terminal end segment encoding the 3′ untranslated region was subcloned by the BP cloning technique and sequenced. The sequencing results showed that all the patients possessed the HLA-B*51011 allele, and there were no differences in the exonic nucleotide sequences between the three Behcet's disease patients and the three healthy controls. The HLA-B*51011 intronic and promoter/enhancer nucleotide sequences from the three patients had 22 single nucleotide polymorphisms (SNPs), a single insertion of 6 bp and a single deletion of 2 bp. On the other hand, the three healthy controls had 24 SNPs in their intronic and promoter/enhancer regions. However, none of these polymorphisms in the patients were specific for the disease. Therefore, these results clearly demonstrate that the HLA-B exonic sequence that encodes the HLA-B51 allele is the real pathogenic factor in Behcet's disease.

  • Localization of the pathogenic gene of Behçet's disease by microsatellite analysis of three different populations.
    Investigative Ophthalmology & Visual Science, 2000
    Co-Authors: Nobuhisa Mizuki, H. Ando, Kazuro Yabuki, Yoshihiko Katsuyama, G. D. Palimeris, Evangelia Kaklamani, Massimo Accorinti, Paola Pivetti-pezzi, Shigeaki Ohno
    Abstract:

    PURPOSE. Behcet's disease (BD) is known to be associated with HLA-B51 in many ethnic groups. However, the pathogenic gene responsible for BD is as yet unknown. To localize the critical region of the pathogenic gene, microsatellite markers distributed around the HLA-B gene were investi- gated. The BD patients studied were of three ethnic origins: Japanese, Greek, or Italian. METHODS. The total group consisted of 172 BD patients, of whom were 95 Japanese, 55 Greek, and 22 Italian. Eight polymorphic microsatellite markers distributed within 1100 kb of the HLA-B gene were analyzed using PCR and subsequent automated fragment detection by fluorescent-based technology. RESULTS. Among the eight markers, allele 348 of the MIB microsatellite was remarkably common in all three BD populations ( Japanese, Pc 5 0.000014; Greek, Pc 5 0.00047; Italian, Pc 5 0.11). However, HLA-B51 was found to be the marker most strongly associated with BD in each population ( Japanese, Pc 5 0.000000000017; Greek, Pc 5 0.00000032; Italian, Pc 5 0.0074). In genotypic differentiation between the patients and controls, only HLA-B51 was found to be significantly associated with BD in all three populations. Stratification analysis suggested that significant associations of BD with MICA and other microsatellites resulted from a linkage disequi- librium with HLA-B51. CONCLUSIONS. These results suggest that the pathogenic gene of BD is HLA-B51 itself and not other genes located in the vicinity of HLA-B. (Invest Ophthalmol Vis Sci. 2000;41:3702-3708)

  • Behçet’s disease, the Silk Road and HLA‐B51: historical and geographical perspectives
    Tissue Antigens, 1999
    Co-Authors: David H. Verity, Shigeaki Ohno, J.e. Marr, Graham R. Wallace, Miles Stanford
    Abstract:

    Behcet’s disease (BD), also known as the Silk Road disease, is a blinding inflammatory disorder of young adults found predominantly between the Mediterranean basin and the Orient, and is strongly associated with the major histocompatibility complex (MHC) antigen HLA-B51. In this article we review the history of Behcet’s disease since its first description by Hippocrates, the development of the trading routes collectively known as the Silk Road and the effect of population movement on the distribution of HLA-B51. The global distribution of this antigen among healthy control populations bears a striking similarity both to the ancient trading routes and the distribution of Behcet’s disease, suggesting a genetic risk that migrated in parallel with population movement between the Mediterranean and Asia. However, certain indigenous Amerindian peoples have a high prevalence of HLA-B51 but no reported cases of BD. Furthermore, a clear genealogical relationship exists between eastern, but not central, Siberian populations with the Amerindians. Since a high level of recombination within the MHC is known to have occurred in these eastern populations before their migration into Beringia, we suggest that disruption of genetic loci in linkage disequilibria with HLA-B51 may be one reason for the absence of disease in these high HLA-B51-bearing populations. However, a contributory influence of environmental factors is not excluded by this data, and the wide variation that exists in relative risk of HLA-B51 even within Europe would support other non-genetic risk factors on the Silk Road which may be absent, or non-contributory to disease, in the Americas.

  • Microsatellite polymorphism within the MICB gene among japanese patients with behçet’s disease
    Human Immunology, 1998
    Co-Authors: Takahiro Kimura, Nobuhisa Mizuki, Hidetoshi Inoko, Kazuro Yabuki, Kaori Goto, Tamiya, Masahiro Sato, Minoru Kimura, Shigeaki Ohno
    Abstract:

    Abstract Behcet’s disease (BD) is known to be associated with HLA-B51. In order to investigate the influence of the MICB gene, located about 120 kb centromeric of the HLA-B gene, on the susceptibility to BD, (CA/TG) dinucleotide repeat microsatellite polymorphism in intron 1 of the MICB gene was investigated among 77 Japanese patients with BD, 60 randomly selected controls and 28 HLA-B51-positive unrelated healthy controls. There was no significant difference in the phenotype frequency of the microsatellite polymorphism between the BD patients and controls. This result suggests that the MICB gene itself is not responsible for the development of BD, and that the candidate gene(s) for BD is located between the MICA and HLA-C genes.

  • triplet repeat polymorphism in the transmembrane region of the mica gene a strong association of six gct repetitions with behcet disease
    Proceedings of the National Academy of Sciences of the United States of America, 1997
    Co-Authors: Nobuhisa Mizuki, H. Ando, Satoshi Nakamura, Shigeaki Ohno, Yoshihiko Katsuyama, Kaori Goto, Minoru Kimura, Masaaki Yamazaki, Koji Watanabe, Seiamak Bahram
    Abstract:

    A member of a novel family of the human major histocompatibility complex (MHC) class I genes termed MIC (MHC class I chain-related genes), MICA, has been recently identified near the HLA-B gene on the short arm of human chromosome 6. The predicted amino acid sequence of the MICA chain suggests that it folds similarly to typical class I chains and may have the capacity to bind peptides or other short ligands. Therefore, MICA is predicted to have a specialized function in antigen presentation or T cell recognition. During nucleotide sequence analyses of the MICA genomic clone, we found a triplet repeat microsatellite polymorphism of (GCT/AGC)n in the transmembrane (TM) region of the MICA gene. In 68 HLA homozygous B cell lines, 5 distinct alleles of this microsatellite sequence were detected. One of them contained an additional one base insertion that created a frameshift mutation resulting in a premature termination codon in the TM region. This particular allele may encode a soluble, secreted form of the MICA molecule. In addition, we have investigated this microsatellite polymorphism in 77 Japanese patients with Behcet disease, which is known to be associated with HLA-B51. The microsatellite allele consisting of 6 repetitions of GCT/AGC was present at significantly higher frequency in the patient group (Pc = 0.00055) than in a control population. Furthermore, the (GCT/AGC)6 allele was present in all B51 positive patients and in an additional 13 B51 negative patients. These results suggest the possibility of a primary association of Behcet disease with MICA rather than HLA-B.

Romano Krueger - One of the best experts on this subject based on the ideXlab platform.

  • a sensitive and rapid alternative to hla typing as a genetic screening test for abacavir hypersensitivity syndrome
    Pharmacogenetics and Genomics, 2006
    Co-Authors: A Martin, Romano Krueger, David Nolan, Coral Ann Almeida, Elizabeth J Phillips, Simon Mallal
    Abstract:

    Background: Abacavir hypersensitivity reaction (ABC HSR) is a potentially life-threatening adverse reaction that affects approximately 8% of patients that initiate this antiretroviral drug. Independent groups have shown a strong predictive association between ABC HSR and HLA-B*5701, indicating that exclusion of HLA-B*5701 positive individuals from abacavir treatment would largely prevent ABC HSR. However, the limited availability and relatively high cost of human leukocyte antigen (HLA) typing represent barriers to the widespread implementation of this pharmacogenetic approach to abacavir prescribing. To facilitate routine screening, we have developed a rapid flow cytometry method for HLA-B57 phenotyping using commercially available B17 monoclonal antibodies. Methods: Whole blood samples from 84 human immunodeficiency virus (HIV)+ patients were examined by standard flow cytometry methods, using a two-colour B17-specific immunofluorescence assay in the CD45+ lymphocyte population. Results: All eight HLA-B57 individuals examined tested positive, while HLA-B57/58 negative individuals (n=74) tested negative for this flow cytometry test. Two non-HLA-B57 individuals showed weak cross-reactivity. Conclusion: In our predominantly Caucasian population, B17/CD45 dual staining was sufficient to identify individuals carrying B17 cell surface antigens. This approach, utilizing flow cytometry methods that are widely available in HIV laboratories, therefore offers a sensitive, rapid and cost-effective screening assay prior to abacavir prescription. Following risk stratification with this assay, it would be anticipated that identification of HLA-B*5701 using molecular HLA typing methods would be required in <10% of the screened population.

  • A sensitive and rapid alternative to HLA typing as a genetic screening test for abacavir hypersensitivity syndrome
    Pharmacogenetics and Genomics, 2006
    Co-Authors: Annalise M. Martin, Romano Krueger, Elizabeth Phillips, David Nolan, Coral Ann Almeida, Simon Mallal
    Abstract:

    BACKGROUND: Abacavir hypersensitivity reaction (ABC HSR) is a potentially life-threatening adverse reaction that affects approximately 8% of patients that initiate this antiretroviral drug. Independent groups have shown a strong predictive association between ABC HSR and HLA-B*5701, indicating that exclusion of HLA-B*5701 positive individuals from abacavir treatment would largely prevent ABC HSR. However, the limited availability and relatively high cost of human leukocyte antigen (HLA) typing represent barriers to the widespread implementation of this pharmacogenetic approach to abacavir prescribing. To facilitate routine screening, we have developed a rapid flow cytometry method for HLA-B57 phenotyping using commercially available B17 monoclonal antibodies. METHODS: Whole blood samples from 84 human immunodeficiency virus (HIV) patients were examined by standard flow cytometry methods, using a two-colour B17-specific immunofluorescence assay in the CD45 lymphocyte population. RESULTS: All eight HLA-B57 individuals examined tested positive, while HLA-B57/58 negative individuals (n=74) tested negative for this flow cytometry test. Two non-HLA-B57 individuals showed weak cross-reactivity. CONCLUSION: In our predominantly Caucasian population, B17/CD45 dual staining was sufficient to identify individuals carrying B17 cell surface antigens. This approach, utilizing flow cytometry methods that are widely available in HIV laboratories, therefore offers a sensitive, rapid and cost-effective screening assay prior to abacavir prescription. Following risk stratification with this assay, it would be anticipated that identification of HLA-B*5701 using molecular HLA typing methods would be required in