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Edoardo Baglivo - One of the best experts on this subject based on the ideXlab platform.
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a shared hla drb1 epitope in the dr beta first domain is associated with vogt koyanagi harada syndrome in indian patients
Molecular Vision, 2010Co-Authors: Jeanmarie Tiercy, Sivakumar R Rathinam, Marianne Gexfabry, Edoardo BaglivoAbstract:PURPOSE: Vogt-Koyanagi-Harada (VKH) disease and sympathetic ophthalmia (SO) are two distinct entities that share common clinical and histopathological features; however, it remains unknown whether they have a common genetic susceptibility. Several studies have shown an association of human leukocyte antigen (HLA)-DR4 with VKH disease in patients of different ethnic backgrounds. We present in this paper the HLA-DRB1 genotyping analysis of a large cohort of VKH patients from southern India and compare these patients to patients with SO and to healthy individuals from the same geographic area. METHODS: VKH patients were diagnosed according to the revised criteria of the International Committee on VKH disease. Patients with granulomatous uveitis after ocular trauma or multiple eye surgeries were diagnosed as having SO. Genomic DNA was extracted from all patients and controls. Samples were analyzed for HLA-DRB1 alleles by reverse polymerase chain reaction (PCR) sequence-specific oligonucleotide (SSO) hybridization on microbeads, using the Luminex technology, and by PCR sequence-specific primers (SSP) typing for DRB1*04 allele determination. Strength of associations was estimated by odds ratios (OR) and 95% confidence intervals (CI) and frequencies were compared using the Fisher's exact test. RESULTS: HLA-DRB1 alleles were determined in 94 VKH patients, 39 SO patients, and 112 healthy controls. HLA-DRB1*04 frequency was higher in VKH patients (20.2% versus 10.3% in controls; OR=2.2, p=0.005, pc=0.067). This association was lower than the association of HLA-DRB1*04 frequency in cohorts of patients from different origins. No significant DR4 association with SO was detected. HLA-DRB1*0405 and HLA-DRB1*0410 alleles were significantly increased in VKH patients (8.5% versus 0.9% in controls; OR=10.3, 95% CI=2.34-45.5, p<0.001). These two alleles share the epitope S57-LLEQRRAA (67-74) in the third hypervariable region of the HLA-DR molecule. None of the DRB1 alleles was significantly associated with SO. CONCLUSIONS: Based on the association of HLA-DRB1*0405 and HLA-DRB1*0410 alleles with VKH disease, we propose that the epitope S57-LLEQRRAA (67-74) in the third hypervariable region of the HLA-DRbeta1 molecule is the relevant susceptibility epitope. This genetic component seems specific to VKH disease since no correlation could be identified in SO patients. The weaker association with HLA-DR4 in this VKH patient cohort compared to VKH patients from northern India is probably related to the lower frequency of HLA-DRB1*0405 in our study group. The HLA-DRB1 association with susceptibility to VKH syndrome seems weaker in Indian patients compared to Japanese or Hispanic patients, suggesting a different non-HLA immunogenetic background in Indian VKH patients.
Jeanmarie Tiercy - One of the best experts on this subject based on the ideXlab platform.
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a shared hla drb1 epitope in the dr beta first domain is associated with vogt koyanagi harada syndrome in indian patients
Molecular Vision, 2010Co-Authors: Jeanmarie Tiercy, Sivakumar R Rathinam, Marianne Gexfabry, Edoardo BaglivoAbstract:PURPOSE: Vogt-Koyanagi-Harada (VKH) disease and sympathetic ophthalmia (SO) are two distinct entities that share common clinical and histopathological features; however, it remains unknown whether they have a common genetic susceptibility. Several studies have shown an association of human leukocyte antigen (HLA)-DR4 with VKH disease in patients of different ethnic backgrounds. We present in this paper the HLA-DRB1 genotyping analysis of a large cohort of VKH patients from southern India and compare these patients to patients with SO and to healthy individuals from the same geographic area. METHODS: VKH patients were diagnosed according to the revised criteria of the International Committee on VKH disease. Patients with granulomatous uveitis after ocular trauma or multiple eye surgeries were diagnosed as having SO. Genomic DNA was extracted from all patients and controls. Samples were analyzed for HLA-DRB1 alleles by reverse polymerase chain reaction (PCR) sequence-specific oligonucleotide (SSO) hybridization on microbeads, using the Luminex technology, and by PCR sequence-specific primers (SSP) typing for DRB1*04 allele determination. Strength of associations was estimated by odds ratios (OR) and 95% confidence intervals (CI) and frequencies were compared using the Fisher's exact test. RESULTS: HLA-DRB1 alleles were determined in 94 VKH patients, 39 SO patients, and 112 healthy controls. HLA-DRB1*04 frequency was higher in VKH patients (20.2% versus 10.3% in controls; OR=2.2, p=0.005, pc=0.067). This association was lower than the association of HLA-DRB1*04 frequency in cohorts of patients from different origins. No significant DR4 association with SO was detected. HLA-DRB1*0405 and HLA-DRB1*0410 alleles were significantly increased in VKH patients (8.5% versus 0.9% in controls; OR=10.3, 95% CI=2.34-45.5, p<0.001). These two alleles share the epitope S57-LLEQRRAA (67-74) in the third hypervariable region of the HLA-DR molecule. None of the DRB1 alleles was significantly associated with SO. CONCLUSIONS: Based on the association of HLA-DRB1*0405 and HLA-DRB1*0410 alleles with VKH disease, we propose that the epitope S57-LLEQRRAA (67-74) in the third hypervariable region of the HLA-DRbeta1 molecule is the relevant susceptibility epitope. This genetic component seems specific to VKH disease since no correlation could be identified in SO patients. The weaker association with HLA-DR4 in this VKH patient cohort compared to VKH patients from northern India is probably related to the lower frequency of HLA-DRB1*0405 in our study group. The HLA-DRB1 association with susceptibility to VKH syndrome seems weaker in Indian patients compared to Japanese or Hispanic patients, suggesting a different non-HLA immunogenetic background in Indian VKH patients.
Peter Parham - One of the best experts on this subject based on the ideXlab platform.
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hla class i variation in iranian lur and kurd populations high haplotype and allotype diversity with an abundance of kir ligands
Human Immunology, 2016Co-Authors: Elham Ashouri, Lisbeth A Guethlein, Paul Norman, Alex S Han, Neda Nematgorgani, Steven Norberg, Abbas Ghaderi, Peter ParhamAbstract:HLA-A , -B and -C alleles of 285 individuals, representing three Iranian Lur populations and one Iranian Kurd population were sequenced completely, yielding HLA class I genotypes at high resolution and filling four fields of the official HLA nomenclature. Each population has 87–99 alleles, evenly distributed between the three HLA class I genes, 145 alleles being identified in total. These alleles were already known, named and deposited in the HLA database. The alleles form 316 different HLA A-B-C haplotypes, with each population having between 80 and 112 haplotypes. The four Iranian populations form a related group that is distinguished from other populations, including other Iranians. All four KIR ligands – the A3/11, Bw4, C1 and C2 epitopes – are well represented, particularly Bw4, which is carried by three high-frequency allotypes: HLA-A ∗ 24:02, HLA-A ∗ 32:01 and HLA-B ∗ 51:01. In the Lur and Kurd populations, between 82% and 94% of individuals have the Bw4 epitope, the ligand for KIR3DL1. HLA-B ∗ 51:01 is of Neandertal origin and associated with Behcet’s disease, also known as the Silk Road disease. The Lordegan Lur have the highest frequency of HLA-B ∗ 51:01 in the world. This allele is present on 46 Lur and Kurd haplotypes. Present at lower frequency is HLA-B ∗ 51:08 , which is also associated with Behcet’s disease. In the four Iranian populations, 31 haplotypes encode both Bw4 + HLA-A and Bw4 + HLA-B, a dual combination of Bw4 epitopes that is relatively rare in other populations, worldwide. This study both demonstrates and emphasizes the value of studying HLA class I polymorphism at highest resolution in anthropologically well-defined populations.
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serologic cross reactivities poorly reflect allelic relationships in the hla b12 and hla b21 groups dominant epitopes of the alpha 2 helix
Journal of Immunology, 1992Co-Authors: William H. Hildebrand, J A Madrigal, Monica P Belich, J Zemmour, F E Ward, R C Williams, Peter ParhamAbstract:Previous analysis has emphasized the correlation between primary structures of class I HLA molecules and their patterns of serologic cross-reactivity. Here we describe the structures of two serologic groups of HLA-B alleles for which this is not the case. HLA-B45, an allele associated with black populations, is serologically paired with B44 in the B12 group; its structure, however, is divergent from that of B44 but closely related to B50. The BN21 (B*4005) allele is associated with native Americans and is serologically grouped with B50 in the B21 group; its structure, however, is more closely related to alleles of the B40 group. The B44 and B45 serologically cross-reactive molecules differ at seven functional positions of the Ag recognition site; the B50 and BN21 molecules differ at four such residues. These differences are predicted to alter peptide presentation and be capable of eliciting strong alloreactive T cell responses. For these pairs of B12 and B21 Ag, serology appears dominated by epitopes formed by short sequences of the alpha 2 helix which have been shuffled by recombination between alleles. The implications of these results for HLA matching in transplantation are discussed.
Giuseppe Masucci - One of the best experts on this subject based on the ideXlab platform.
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swedish ovarian cancer patients are found with a high frequency of human leucocyte antigen hla a2 b7 b12 b15 b44 and drb1 4 haplotypes
Journal of Clinical Oncology, 2006Co-Authors: Kjell Bergfeldt, Z Gamzatova, B Tholander, M Bergdahl, B Nordstrom, E Hjerpe, Giuseppe MasucciAbstract:20100 Background: There is an increased interest on the association between HLA markers and prognostic outcome in several cancer forms. We have previously reported that the high prevalence of the A...
Ole Weis Bjerrum - One of the best experts on this subject based on the ideXlab platform.
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human neutrophil structure and function with special reference to cytochrome b559 and beta 2 microglobulin
Danish Medical Bulletin, 1993Co-Authors: Ole Weis BjerrumAbstract:: Neutrophil granulocytes are the most important white blood cells in the combat of non-viral infections. Circumstantial evidence indicates that neutrophils in addition modulate the inflammatory process. Production of neutrophils takes place in the bone marrow, and mature cells egress to the circulation. Neutrophils emigrate following activation from the vessels into the tissues (chemotaxis). During this process neutrophils generate reactive oxygen species (respiratory burst) and mobilize intracellular compartments (degranulation). By degranulation, neutrophils exercise influence on nearby cells or bacteria by extracellular release of intragranular proteins (exocytosis), and intensify plasma membrane-related processes, such as chemotaxis and respiratory burst, by translocation of membrane-bound proteins to the surface (upregulation). Ultimately, microorganisms may be killed intracellularly following engulfment (phagocytosis). The thesis presents results of protein-chemical analysis of human neutrophils, based on studies of intact cells and subcellular structures (subcellular fractionation). By fractionation, azurophil granules and specific granules can be disunited from each other and from plasma membrane and secretory vesicles. Only partial separation of plasma membrane and secretory vesicles can be obtained. Subcellular structures are identified by markers, e.g. vitamin B12 binding protein for specific granules, and latent alkaline phosphatase for secretory vesicles. The studies demonstrated tetranectin in neutrophils, localized exclusively in the secretory vesicles. Tetranectin was released by incubation of neutrophils in the presence of weak, inflammatory stimuli and paralleled the upregulation of alkaline phosphatase, but preceded degranulation of specific granules. Alkaline phosphatase has previously been employed as a plasma membrane marker. A novel ELISA for HLA class I antigen was introduced as a new plasma membrane marker. Results obtained by this assay showed upregulation of alkaline phosphatase occurring without a concurrent redistribution of HLA antigen. This indicates that the two proteins are localized in separate compartments. Upregulation of alkaline phosphatase induced by weak stimuli, however, paralleled the translocation of cytochrome b559, anticipated to be the terminal component in the respiratory burst, and known to be localized primarily in the specific granules. The present studies indicate that 15% of cytochrome b is localized in the secretory vesicles. An ELISA was established for quantitation of beta 2-microglobulin, the light chain of HLA class I antigens. The concentration of beta 2-microglobulin in plasma from patients with chronic myeloid leukaemia was found to correlate with the concentration of vitamin B12 binding protein.4+ Measurements in neutrophils demonstrated 65% of the total content of beta 2-microglobulin to be localized in the specific granules, and 20% to be present in secretory vesicles.(ABSTRACT TRUNCATED AT 400 WORDS)