Evidence of HLA-DQB1 Contribution to Susceptibility of Dengue Serotype 3 in Dengue Patients in Southern Brazil

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Daniela Maria Cardozo

2014-01-01

Full Text Available Dengue infection (DI transmitted by arthropod vectors is the viral disease with the highest incidence throughout the world, an estimated 300 million cases per year. In addition to environmental factors, genetic factors may also influence the manifestation of the disease; as even in endemic areas, only a small proportion of people develop the most serious form. Immune-response gene polymorphisms may be associated with the development of cases of DI. The aim of this study was to determine allele frequencies in the HLA-A, B, C, DRB1, DQA1, and DQB1 loci in a Southern Brazil population with dengue virus serotype 3, confirmed by the ELISA serological method, and a control group. The identification of the HLA alleles was carried out using the SSO genotyping PCR program (One Lambda, based on Luminex technology. In conclusion, this study suggests that DQB1*06:11 allele could act as susceptible factors to dengue virus serotype 3, while HLA-DRB1*11 and DQA1*05:01 could act as resistance factors.

Environmental toxins and risk of narcolepsy among people with HLA DQB1*0602

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Ton, Thanh G.N.; Longstreth, WT; Koepsell, Thomas D.

2010-01-01

One etiologic model for narcolepsy suggests that some environmental toxin selectively and irreversibly destroys hypocretin-producing cells in individuals with human leukocyte antigen (HLA) DQB1*0602. Between 2001-2005, the authors conducted a population-based case-control study in King County, Washington to examine narcolepsy risk in relation to toxins found in jobs, hobbies and other non-vocational activities. Sixty-seven cases and 95 controls were enrolled; all were between ages 18-50 and positive for HLA DQB1*0602. All were administered in-person interviews about jobs, hobbies or other non-vocational activities before age 21. All analyses were adjusted for African American race and income. Risk increased significantly for jobs involving heavy metals (odds ratio [OR]=4.7; 95% confidence interval [CI]: 1.5, 14.5) and for highest levels of exposure to woodwork (OR: 3.0; 95% CI: 1.0, 8.9), fertilizer (OR=3.1; 95% CI: 1.1, 9.1), and bug or weed killer (OR=4.5; 95% CI: 1.5, 13.4). Associations were of borderline significance for activities involving ceramics, pesticides, and painting projects. Significant dose-response relationships were evident for jobs involving metals (p<0.03), paints (p<0.03), and bug or weed killer (p<0.02). Additional studies are needed to replicate these findings and continue the search for specific toxins that could damage hypocretin neurons in genetically susceptible people. PMID:20519130

Different DRB1*03:01-DQB1*02:01 haplotypes confer different risk for celiac disease.

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Alshiekh, S; Zhao, L P; Lernmark, Å; Geraghty, D E; Naluai, Å T; Agardh, D

2017-08-01

Celiac disease is associated with the HLA-DR3-DQA1*05:01-DQB1*02:01 and DR4-DQA1*03:01-DQB1*03:02 haplotypes. In addition, there are currently over 40 non-HLA loci associated with celiac disease. This study extends previous analyses on different HLA haplotypes in celiac disease using next generation targeted sequencing. Included were 143 patients with celiac disease and 135 non-celiac disease controls investigated at median 9.8 years (1.4-18.3 years). PCR-based amplification of HLA and sequencing with Illumina MiSeq technology were used for extended sequencing of the HLA class II haplotypes HLA-DRB1, DRB3, DRB4, DRB5, DQA1 and DQB1, respectively. Odds ratios were computed marginally for every allele and haplotype as the ratio of allelic frequency in patients and controls as ratio of exposure rates (RR), when comparing a null reference with equal exposure rates in cases and controls. Among the extended HLA haplotypes, the strongest risk haplotype for celiac disease was shown for DRB3*01:01:02 in linkage with DQA1*05:01-DQB1*02:01 (RR = 6.34; P-value celiac disease among non-Scandinavians (RR = 7.94; P = .011). The data also revealed 2 distinct celiac disease risk DR3-DQA1*05:01-DQB*02:01 haplotypes distinguished by either the DRB3*01:01:02 or DRB3*02:02:01 alleles, indicating that different DRB1*03:01-DQB1*02:01 haplotypes confer different risk for celiac disease. The associated risk of celiac disease for DR3-DRB3*01:01:02-DQA1*05:01-DQB1*02:01 is predominant among patients of Scandinavian ethnicity. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Pharmacogenetic tests to predict the efficacy of aspirin desensitization in patients with aspirin-exacerbated respiratory diseases; HLA-DQB302.

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Esmaeilzadeh, Hossein; Nabavi, Mohammad; Aryan, Zahra; Amirzargar, Ali Akbar

2015-10-01

This study is aimed at investigating the association of HLA-DRB1, HLA-DQA1, and HLA-DQB1 variability with the response to aspirin desensitization (AD). A total of 16 patients with aspirin-exacerbated respiratory diseases (AERD, 81.3% were female) with median age of 29 ± 4.3 years were included in this study. Following 6 months, Sino-Nasal Outcome Test-22 (SNOT-22), medication, symptom scores, and forced expiratory volume in 1 s (FEV1) (all p < 0.001) improved significantly. However, only seven patients (43.7%) had clinically significant improvement in all of the medication and symptom scores and FEV1, who were considered responders to AD. Responders to AD had significantly higher symptom scores compared with non-responders at baseline (20 ± 1.18 vs 10 ± 1.27; p = 0.003). HLADQB1*0302 was significantly lower in non-responders than in responders to AD (0.12 [0.02-0.76]; p = 0.022). Sensitivity and specificity of HLA-DQB1*0302 to predict response to AD was 71.4% (95% CI: 35.8-91.7) and 81.8% (95% CI: 52.3-94.8). This study introduces HLA-DQB1*0302 as a genetic marker for favorable response to AD.

Allele variants of HLA II genes DRB1 and DQB1 regarding risk for type 1 diabetes mellitus in population of Bashkortostan

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Shamilevna Avzaletdinova

2012-09-01

Full Text Available Aims. To estimate significance of HLA II DRB1 and DRB2 allele variants for development of type 1 diabetes mellitus (T1DM in Bashkortostanpopulation (ethnical Russians, Tatar, Bashkir. Materials and methods. We analyzed DNA of 323 patients with T1DM and 683 healthy controls. DNA was derived from venous bloodsamples by phenol-chloroform extraction. DRB1 and DQB1 gene typing was performed by PCR method. Amplification products wereidentified with electrophoresis on a 1% agarose gel. Statistica for Windows v6.0 and MS Excel 98 software were applied for statisticalprocessing of acquired data. Results. Common markers of high risk for T1DM were found to be DRB1*04, DRB1*17, genotype DRB1*04/*17. On the contrary,lower risk was associated with DRB1*15 allele. In ethnical Russians lower risk of T1DM is also determined by DRB1*11 allele andDRB1*01 in Tatars. Predisposition by DQB1-alleles in Russians and Bashkir realizes only within DRB1*04/*17 genotype. However,in Tatar subpopulation DQB1*0302 is an independent risk marker of T1DM development. Conclusion. Common low risk markers for all three ethnic groups are DQB1*0301, DQB1*0602-08 alleles. Their presence negates riskof disease in all studied subpopulations even within DRB1*04/*17-genotype.

The DQB1 *03:02 HLA haplotype is associated with increased risk of chronic pain after inguinal hernia surgery and lumbar disc herniation.

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Dominguez, Cecilia A; Kalliomäki, Maija; Gunnarsson, Ulf; Moen, Aurora; Sandblom, Gabriel; Kockum, Ingrid; Lavant, Ewa; Olsson, Tomas; Nyberg, Fred; Rygh, Lars Jørgen; Røe, Cecilie; Gjerstad, Johannes; Gordh, Torsten; Piehl, Fredrik

2013-03-01

Neuropathic pain conditions are common after nerve injuries and are suggested to be regulated in part by genetic factors. We have previously demonstrated a strong genetic influence of the rat major histocompatibility complex on development of neuropathic pain behavior after peripheral nerve injury. In order to study if the corresponding human leukocyte antigen complex (HLA) also influences susceptibility to pain, we performed an association study in patients that had undergone surgery for inguinal hernia (n=189). One group had developed a chronic pain state following the surgical procedure, while the control group had undergone the same type of operation, without any persistent pain. HLA DRB1genotyping revealed a significantly increased proportion of patients in the pain group carrying DRB1*04 compared to patients in the pain-free group. Additional typing of the DQB1 gene further strengthened the association; carriers of the DQB1*03:02 allele together with DRB1*04 displayed an increased risk of postsurgery pain with an odds risk of 3.16 (1.61-6.22) compared to noncarriers. This finding was subsequently replicated in the clinical material of patients with lumbar disc herniation (n=258), where carriers of the DQB1*03:02 allele displayed a slower recovery and increased pain. In conclusion, we here for the first time demonstrate that there is an HLA-dependent risk of developing pain after surgery or lumbar disc herniation; mediated by the DRB1*04 - DQB1*03:02 haplotype. Further experimental and clinical studies are needed to fine-map the HLA effect and to address underlying mechanisms. Copyright © 2012 International Association for the Study of Pain. Published by Elsevier B.V. All rights reserved.

Molecular variation at the HLA-A, B, C, DRB1, DQA1, and DQB1 loci in full heritage American Indians in Arizona: private haplotypes and their evolution.

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Williams, R; Chen, Y-F; Endres, R; Middleton, D; Trucco, M; Williams, J Dunn; Knowler, W

2009-12-01

A sample of 492 full heritage, unrelated residents of the Gila River Indian Community (GRIC) of Arizona were characterized for their high-resolution DNA alleles at the HLA-A, B, C, DRB1, DQA1, and DQB1 loci. Only five allelic categories are found at HLA-A, 10 at HLA-B, 8 at HLA-C and HLA-DR, and 4 at DQA1 and DQB1. There is little evidence for population structure at the 6 loci. Two 'private' alleles, B*5102 and B*4005, which are found nearly exclusively in American Indian populations in the desert southwest and northern Mexico, are likely new mutations after the first inhabitation of the area, the evolution of which are reflected in the contemporary distribution of their respective haplotypes. DRB1*1402 has the highest reported frequency of any specificity at the DRB1 locus, 0.7461, and serves as a sensitive probe for locating related east Asian populations. The haplotypes in this population also exhibit a highly restricted distribution and strong genetic disequilibria, which has important implications for matching solid organ and bone marrow allografts. It is shown that, when one considers HLA-A-B-DRB1 homozygotes as allograft donors for all full heritage members of the GRIC, 50% of the community would find a non-mismatched organ within the homozygotes for the six most common haplotypes. This raises questions about transplantation policy and whether, in the presence of high-frequency private alleles and a restricted number of haplotypes, the full heritage American Indian community of the desert southwest should act as its own pool of donors for its affected members.

HLA-DRB and HLA-DQ genetic variability in patients with aspirin-exacerbated respiratory disease.

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Esmaeilzadeh, Hossein; Nabavi, Mohammad; Amirzargar, Ali Akbar; Aryan, Zahra; Arshi, Saba; Bemanian, Mohammad Hassan; Fallahpour, Morteza; Mortazavi, Negar; Rezaei, Nima

2015-01-01

Major histocompatibility complex (MHC) class II is involved in T-cell activation, cytokine secretion, and induction of immune responses. Cytokines, staphylococcus super antigens, and eosinophil activation are proposed to play important roles in aspirin-exacerbated respiratory disease (AERD). This study is aimed at investigating the association of HLA-DRB and DQ genetic variabilities in patients with AERD. A genetic association analysis in three different groups, including 33 patients with AERD, 17 patients with aspirin-tolerant asthma (ATA), and 100 healthy controls was performed. Oral aspirin challenge (OAC) test was performed to identify aspirin hypersensitivity. Pulmonary function test (PFT) was performed for all patients. Eosinophil percentage in nasal smear and peripheral blood and serum immunoglobin (Ig)E were investigated. HLA-DRB, HLA-DQA1, and HLA-DQB1 were genotyped using polymerase chain reaction. HLA-DQB1*0302 (OR, 5.49, 95% confidence interval [CI],(2.40-12.59)), HLA-DQA1*0301 (OR, 2.90, 95% CI, (1.49-5.67)), HLA-DRB4 (OR, 2.94, 95% CI, (1.61-5.36)), and HLA-DRB1*04 (OR, 3.19, 95% CI, (1.57-6.47)) were higher in patients with AERD compared with controls. In patients with AERD, HLA-DQB1*0301 (OR,0.22, 95% CI, (0.09-0.54)), HLA-DQA1*0501 (OR, 0.42, 95% CI, (0.21-0.81)), HLA-DRB1*11 (OR, 0.30, 95% CI, (0.12-0.73)), and HLA-DRB3 (OR, 0.38, 95% CI, (0.21-0.70)) were significantly lower compared with healthy controls. Patients with AERD had lower frequencies of HLA-DQB1*0301 (OR, 0.27, 95% CI, (0.08-0.86)), and HLA-DRB1*011 (OR, 0.27, 95% CI, (0.08-0.86)) compared with ATA. Haplotypes of HLA-DRB1*04/ DQA1*0301/ DQB1*0302 (OR, 4.25, 95% CI, (1.94-9.29)) and HLA-DRB1*07 /DQA1*0201/ DQB1*0201 (OR, 3.52, 95% CI, (1.54-8.06)) were higher in patients with AERD compared with controls (all p < 0.05). Results of this study suggest that HLA-DQB1*0302 and HLA-DRB1*04 and their related haplotypes are genes involved in predisposing patients to AERD, whereas HLA-DQB1

Human Leukocyte Antigen-A, B, C, DRB1, and DQB1 Allele and Haplotype Frequencies in a Subset of 237 Donors in the South African Bone Marrow Registry

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Mqondisi Tshabalala

2018-01-01

Full Text Available Human leukocyte antigen- (HLA- A, HLA-B, HLA-C, HLA-DRB1, and HLA-DQB1 allele and haplotype frequencies were studied in a subset of 237 volunteer bone marrow donors registered at the South African Bone Marrow Registry (SABMR. Hapl-o-Mat software was used to compute allele and haplotype frequencies from individuals typed at various resolutions, with some alleles in multiple allele code (MAC format. Four hundred and thirty-eight HLA-A, 235 HLA-B, 234 HLA-DRB1, 41 HLA-DQB1, and 29 HLA-C alleles are reported. The most frequent alleles were A∗02:02g (0.096, B∗07:02g (0.082, C∗07:02g (0.180, DQB1∗06:02 (0.157, and DRB1∗15:01 (0.072. The most common haplotype was A∗03:01g~B∗07:02g~C∗07:02g~DQB1∗06:02~DRB1∗15:01 (0.067, which has also been reported in other populations. Deviations from Hardy-Weinberg equilibrium were observed in A, B, and DRB1 loci, with C~DQB1 being the only locus pair in linkage disequilibrium. This study describes allele and haplotype frequencies from a subset of donors registered at SABMR, the only active bone marrow donor registry in Africa. Although the sample size was small, our results form a key resource for future population studies, disease association studies, and donor recruitment strategies.

Persistent HPV16/18 infection in Indian women with the A-allele (rs6457617) of HLA-DQB1 and T-allele (rs16944) of IL-1β -511 is associated with development of cervical carcinoma.

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Dutta, Sankhadeep; Chakraborty, Chandraditya; Mandal, Ranajit Kumar; Basu, Partha; Biswas, Jaydip; Roychoudhury, Susanta; Panda, Chinmay Kumar

2015-07-01

The aim of this study was to understand the association of human papillomavirus (HPV) type 16/18 infection and polymorphisms in the HLA-DQB1 (rs6457617) and IL-1β -511 (rs16944) loci with the development of uterine cervical cancer (CaCx). The distribution of HLA-DQB1 G > A and IL-1β -511 C/T polymorphisms was determined in HPV-negative cervical swabs from normal women (N = 111) and compared with cervical swabs of HPV-cleared normal women (once HPV infected followed by natural clearance of the infection, N = 86), HPV16/18-positive cervical intraepithelial neoplasia (CIN, N = 41) and CaCx biopsies (N = 107). The A-allele containing genotypes (i.e. G/A and A/A) of HLA-DQB1 was significantly associated with CaCx compared with HPV-negative [OR = 2.56(1.42-4.62), p = 0.001] or HPV-cleared [OR = 2.07(1.12-3.87), p = 0.01] normal women, whereas the T-allele containing genotypes (i.e. C/T and T/T) of IL-1β showed increased risk of CIN [OR = 3.68(0.97-16.35), p = 0.03; OR = 3.59(0.92-16.38), p = 0.03] and CaCx development [OR = 2.03(1.03-5.2), p = 0.02; OR = 2.25(0.96-5.31), p = 0.04] compared with HPV-negative or HPV-cleared normal women. Considering these two loci together, it was evident that the T- and A-alleles rendered significantly increased susceptibility for development of CIN and CaCx compared with HPV-negative and HPV-cleared normal women. Moreover, the T-allele of IL-1β showed increased susceptibility for CIN [OR = 3.62(0.85-17.95), p = 0.04] and CaCx [OR = 2.39(0.91-6.37), p = 0.05] development compared with the HPV-cleared women, even in the presence of the HLA-DQB1 G-allele. Thus, our data suggest that persistent HPV16/18 infection in the cervix due to the presence of the HLA-DQB1 A-allele and chronic inflammation due to the presence of the IL-1β -511 T-allele might predispose women to CaCx development.

HLA-DRB1*15:01-DQA1*01:02-DQB1*06:02 Haplotype Protects Autoantibody-Positive Relatives From Type 1 Diabetes Throughout the Stages of Disease Progression.

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Pugliese, Alberto; Boulware, David; Yu, Liping; Babu, Sunanda; Steck, Andrea K; Becker, Dorothy; Rodriguez, Henry; DiMeglio, Linda; Evans-Molina, Carmella; Harrison, Leonard C; Schatz, Desmond; Palmer, Jerry P; Greenbaum, Carla; Eisenbarth, George S; Sosenko, Jay M

2016-04-01

The HLA-DRB1*15:01-DQA1*01:02-DQB1*06:02 haplotype is linked to protection from the development of type 1 diabetes (T1D). However, it is not known at which stages in the natural history of T1D development this haplotype affords protection. We examined a cohort of 3,358 autoantibody-positive relatives of T1D patients in the Pathway to Prevention (PTP) Study of the Type 1 Diabetes TrialNet. The PTP study examines risk factors for T1D and disease progression in relatives. HLA typing revealed that 155 relatives carried this protective haplotype. A comparison with 60 autoantibody-negative relatives suggested protection from autoantibody development. Moreover, the relatives with DRB1*15:01-DQA1*01:02-DQB1*06:02 less frequently expressed autoantibodies associated with higher T1D risk, were less likely to have multiple autoantibodies at baseline, and rarely converted from single to multiple autoantibody positivity on follow-up. These relatives also had lower frequencies of metabolic abnormalities at baseline and exhibited no overall metabolic worsening on follow-up. Ultimately, they had a very low 5-year cumulative incidence of T1D. In conclusion, the protective influence of DRB1*15:01-DQA1*01:02-DQB1*06:02 spans from autoantibody development through all stages of progression, and relatives with this allele only rarely develop T1D. © 2016 by the American Diabetes Association. Readers may use this article as long as the work is properly cited, the use is educational and not for profit, and the work is not altered.

Polymorphism of HLA in the Romanian population.

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Reed, E; Ho, E; Lupu, F; McManus, P; Vasilescu, R; Foca-Rodi, A; Suciu-Foca, N

1992-01-01

We have investigated the HLA-class I and class II polymorphism in a population of 83 Romanians using conventional serology together with PCR amplification and oligonucleotide typing of HLA-class II genes. Romanians show a higher frequency of HLA-A11, B13, B18, B37, B39, B51 and DR2 than other European populations. HLA-DRB1*1501 and 1601 account for the high frequency of the serologic specificity DR2. In Romanians, HLA-DR2 is in linkage disequilibrium with HLA-B18 and HLA-Bw52 rather than with HLA-B7 as in the case in other Europeans. Unexpected HLA-DR2 haplotypes include HLA-DRB1*1502, DQA1*0102, DQB1*0601; HLA-DRB1*1602, DQA1*0102, DQB1*0502. Other unusual haplotypes include HLA-DRB1*0405, DQA1*03, DQB1*0302; HLA-DRB1*1305, DQA1*0103, DQB1*0603; and HLA-DRB1*1405, DQA1*0101, DQB1*05032. Analysis of the genetic distance between Romanians and other Europeans who have been studied serologically are consistent with the hypothesis that Romanians descend from Roman ancestors who colonized Dacia between the 1st century B.C. and 1st century A.D.

Human Leukocyte Antigen Class II Alleles (DQB1 and DRB1 as Predictors for Response to Interferon Therapy in HCV Genotype 4

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Olfat Shaker

2013-01-01

Full Text Available Human leukocyte antigens class II play an important role in immune response against HCV. We investigated whether HLA class II alleles influence susceptibility to HCV infection and response to interferon therapy. HLA-DRB1 and -DQB1 loci were genotyped using PCR-SSO Luminex technology. According to our regimen, 41 (66% of patients achieved sustained virological response to combined treatment of IFN and ribavirin. Frequencies of DQB1*0313 allele and DRB1*04-DRB1*11, DQB1*0204-DQB1*0313, DQB1*0309-DQB1*0313, and DQB1*0313-DQB1*0319 haplotypes were significantly more frequent in nonresponders than in responders. In contrast, DQB1*02, DQB1*06, DRB1*13, and DRB1*15 alleles were significantly more frequent in responders than in nonresponders. Similarly, DRB1*1301, DRB1*1361, and DRB1*1369 alleles and DRB1*1301-DRB1*1328, DRB1*1301-DRB1*1361, DRB1*1301-DRB1*1369, DRB1*1328-DRB1*1361, and DRB1*1328-DRB1*1369 haplotypes were significantly found only in responders. Some alleles and linkages showed significantly different distributions between patient and healthy groups. These alleles may be used as predictors for response to treatment or to susceptibility to HCV infection in the Egyptian population.

Absence of autoreactive CD4(+) T-cells targeting HLA-DQA1*01:02/DQB1*06:02 restricted hypocretin/orexin epitopes in narcolepsy type 1 when detected by EliSpot

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Kornum, Birgitte Rahbek; Burgdorf, Kristoffer Sølvsten; Holm, Anja

2017-01-01

Narcolepsy type 1, a neurological sleep disorder strongly associated with Human Leukocyte Antigen (HLA-)DQB1*06:02, is caused by the loss of hypothalamic neurons producing the wake-promoting neuropeptide hypocretin (hcrt, also known as orexin). This loss is believed to be caused by an autoimmune...... reaction. To test whether hcrt itself could be a possible target in the autoimmune attack, CD4(+) T-cell reactivity towards six different 15-mer peptides from prepro-hypocretin with high predicted affinity to the DQA1*01:02/DQB1*06:02 MHC class II dimer was tested using EliSpot in a cohort of 22 narcolepsy...

Absence of autoreactive CD4+ T-cells targeting HLA-DQA1*01:02/DQB1*06:02 restricted hypocretin/orexin epitopes in narcolepsy type 1 when detected by EliSpot.

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Kornum, Birgitte Rahbek; Burgdorf, Kristoffer Sølvsten; Holm, Anja; Ullum, Henrik; Jennum, Poul; Knudsen, Stine

2017-08-15

Narcolepsy type 1, a neurological sleep disorder strongly associated with Human Leukocyte Antigen (HLA-)DQB1*06:02, is caused by the loss of hypothalamic neurons producing the wake-promoting neuropeptide hypocretin (hcrt, also known as orexin). This loss is believed to be caused by an autoimmune reaction. To test whether hcrt itself could be a possible target in the autoimmune attack, CD4 + T-cell reactivity towards six different 15-mer peptides from prepro-hypocretin with high predicted affinity to the DQA1*01:02/DQB1*06:02 MHC class II dimer was tested using EliSpot in a cohort of 22 narcolepsy patients with low CSF hcrt levels, and 23 DQB1*06:02 positive healthy controls. Our ELISpot assay had a detection limit of 1:10,000 cells. We present data showing that autoreactive CD4 + T-cells targeting epitopes from the hcrt precursor in the context of MHC-DQA1*01:02/DQB1*06:02 are either not present or present in a frequency is <1:10,000 among peripheral CD4 + T-cells from narcolepsy type 1 patients. Copyright © 2017 Elsevier B.V. All rights reserved.

Determinação de autoanticorpos para antígenos da mielina no soro de pacientes HLA - DQB1*0602 com esclerose múltipla

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Carvalho Adriana

2003-01-01

Full Text Available Esclerose múltipla (EM é doença inflamatória desmielinizante do sistema nervoso central (SNC de natureza autoimune, mediada por linfócitos Th1. A produção de autoanticorpos séricos para proteína básica da mielina (MBP, proteolipídeo PLP e sequência da glicoproteína de oligodendrócito MOG 92-106, foi determinada em 54 indivíduos saudáveis e 26 pacientes com EM expressando ou não o alelo de suscetibilidade HLA-DQB1*0602. Independentemente da expressão do alelo DQB1*0602, todos os pacientes apresentaram produção marcante (p< 0,0001 de autoanticorpos isotipo IgG para MBP e MOG 92-106, e do isotipo IgA para PLP e MOG 92-106. Os resultados sugerem que outros alelos HLA da classe II exerçam influência na suscetibilidade à EM e no reconhecimento imunológico dos antígenos encefalitogênicos, determinando o padrão de resposta autoimune e contribuindo na manutenção e/ou controle da inflamação no SNC.

Strain-based HLA association analysis identified HLA-DRB1*09:01 associated with modern strain tuberculosis.

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Toyo-Oka, L; Mahasirimongkol, S; Yanai, H; Mushiroda, T; Wattanapokayakit, S; Wichukchinda, N; Yamada, N; Smittipat, N; Juthayothin, T; Palittapongarnpim, P; Nedsuwan, S; Kantipong, P; Takahashi, A; Kubo, M; Sawanpanyalert, P; Tokunaga, K

2017-09-01

Tuberculosis (TB) occurs as a result of complex interactions between the host immune system and pathogen virulence factors. Human leukocyte antigen (HLA) class II molecules play an important role in the host immune system. However, no study has assessed the association between HLA class II genes and susceptibility to TB caused by specific strains. This study investigated the possible association of HLA class II genes with TB caused by modern and ancient Mycobacterium tuberculosis (MTB). The study included 682 patients with TB and 836 control subjects who were typed for HLA-DRB1 and HLA-DQB1 alleles. MTB strains were classified using a large sequence polymorphism typing method. Association analysis was performed using common HLA alleles and haplotypes in different MTB strains. HLA association analysis of patients infected with modern MTB strains showed significant association for HLA-DRB1*09:01 (odds ratio [OR] = 1.82; P-value = 9.88 × 10 -4 ) and HLA-DQB1*03:03 alleles (OR = 1.76; P-value = 1.31 × 10 -3 ) with susceptibility to TB. Haplotype analysis confirmed that these alleles were in strong linkage disequilibrium and did not exert an interactive effect. Thus, the results of this study showed an association between HLA class II genes and susceptibility to TB caused by modern MTB strains, suggesting the importance of strain-specific analysis to determine susceptibility genes associated with TB. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

HLA class II alleles as markers of tuberculosis susceptibility and resistance

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R. Duarte

2011-01-01

Full Text Available Background: Not every individual exposed to Mycobacterium tuberculosis becomes infected. One host genetic factor, involved in modulating the immune response that has been studied in many ethnic groups is the association of human leukocyte antigens (HLA with susceptibility to tuberculosis (TB. Objective: To investigate the association between TB, HLA-DRB1 and HLA-DQB1 alleles in a Portuguese population. Methods: HLA-DRB1 and HLA-DQB1 gene polymorphisms were analyzed by PCR-SSP in 92 TB patients, and 82 healthcare professionals without TB but exposed on a daily basis to infectious patients for more than two years (healthy exposed - HE. Tuberculin skin test reaction (TST, was positive in 69 individuals (all over 15 mm in the HE group (HE+ and negative in thirteen (HE−. Results: HLA-DRB1*14 frequency is higher in the TB patients group (7 % vs. 0; p = 0.038 than in HE+. Conclusions: No genetic marker clearly indicative of disease susceptibility or resistance was identified in this study. However, HLA-DRB1*14 was more frequent in TB patients suggesting that it may be involved in the evolution infection towards active TB in our population. Resumo: Introdução: Nem todos os indivíduos expostos ao Mycobacterium tuberculosis ficam infectados. Um dos factores genéticos envolvidos na modulação da resposta imune e estudado em muitos grupos étnicos é a associação entre moléculas HLA (human leukocyte antigens e a susceptibilidade à tuberculose (TB. Objectivo: Investigar a relação entre TB e os alelos HLA-DRB1, DQB1 numa população Portuguesa.Métodos: Os polimorfismos dos genes HLA-DRB1 e HLA-DQB1 foram analisados por PCR-SSP em 92 doentes com TB e 82 profissionais de saúde saudáveis, expostos diariamente a doentes baciliferos por um período superior a 2 anos (expostos saudáveis: ES. Neste grupo de ES, o teste tuberculínico foi positivo (TST = 10 mm em 69 indivíduos (todos

HLA-DPB1 and HLA class I confer risk of and protection from narcolepsy

DEFF Research Database (Denmark)

Ollila, Hanna M; Ravel, Jean-Marie; Han, Fang

2015-01-01

Type 1 narcolepsy, a disorder caused by a lack of hypocretin (orexin), is so strongly associated with human leukocyte antigen (HLA) class II HLA-DQA1(∗)01:02-DQB1(∗)06:02 (DQ0602) that very few non-DQ0602 cases have been reported. A known triggering factor for narcolepsy is pandemic 2009 influenza......-class-II-independent associations with HLA-A(∗)11:01 (OR = 1.32 [1.13-1.54], p = 4.92 × 10(-4)), HLA-B(∗)35:03 (OR = 1.96 [1.41-2.70], p = 5.14 × 10(-5)), and HLA-B(∗)51:01 (OR = 1.49 [1.25-1.78], p = 1.09 × 10(-5)) were also seen across ethnic groups in the HLA class I region. These effects might reflect modulation...... of autoimmunity or indirect effects of HLA class I and HLA-DP alleles on response to viral infections such as that of influenza....

Using high-resolution human leukocyte antigen typing of 11,423 randomized unrelated individuals to determine allelic varieties, deduce probable human leukocyte antigen haplotypes, and observe linkage disequilibria between human leukocyte antigen-B and-C and human leukocyte antigen-DRB1 and-DQB1 alleles in the Taiwanese Chinese population

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Kuo-Liang Yang

2017-01-01

Full Text Available Objective: We report here the human leukocyte antigen (HLA allelic variety and haplotype composition in a cohort of the Taiwanese Chinese population and their patterns of linkage disequilibria on HLA-B: HLA-C alleles and HLA-DRB1: HLA-DQB1 alleles at a high-resolution level. Materials and Methods: Peripheral whole blood from 11,423 Taiwanese Chinese unrelated individuals was collected in acid citrate dextrose. Genomic DNA was extracted using the QIAamp DNA Blood Mini Kit. The DNA material was subjected to HLA genotyping for HLA-A,-B,-C,-DRB1, and-DQB1 loci using a commercial polymerase chain reaction-sequence-based typing (PCR-SBT kit, the SeCore® A/B/C/DRB1/DQB1 Locus Sequencing kit. High-resolution allelic sequencing was performed as previously described. Results: The number of individual HLA-B alleles detected was greater than the number of alleles recognized in the both the HLA-A and-DRB1 loci. Several novel alleles were discovered as a result of employing the SBT method and the high number of donors tested. In addition, we observed a genetic polymorphic feature of association between HLA-A and-B, HLA-B and-C, and HLA-DRB1 and-DQB1 alleles. Further, the homozygous haplotype frequencies of HLA-A and-B; HLA-A,-C, and-B; HLA-A,-C,-B, and-DRB1; and HLA-A,-C,-B,-DRB1, and-DQB1 in Taiwanese Chinese population are presented. Conclusion: As increasing number of HLA alleles are being discovered, periodic HLA profile investigation in a given population is essential to recognize the HLA complexity in that population. Population study can also provide an up-to-date strategic plan for future needs in terms of compatibility measurement for HLA matching between transplant donors and patients.

Class II HLA interactions modulate genetic risk for multiple sclerosis

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Dilthey, Alexander T; Xifara, Dionysia K; Ban, Maria; Shah, Tejas S; Patsopoulos, Nikolaos A; Alfredsson, Lars; Anderson, Carl A; Attfield, Katherine E; Baranzini, Sergio E; Barrett, Jeffrey; Binder, Thomas M C; Booth, David; Buck, Dorothea; Celius, Elisabeth G; Cotsapas, Chris; D’Alfonso, Sandra; Dendrou, Calliope A; Donnelly, Peter; Dubois, Bénédicte; Fontaine, Bertrand; Fugger, Lars; Goris, An; Gourraud, Pierre-Antoine; Graetz, Christiane; Hemmer, Bernhard; Hillert, Jan; Kockum, Ingrid; Leslie, Stephen; Lill, Christina M; Martinelli-Boneschi, Filippo; Oksenberg, Jorge R; Olsson, Tomas; Oturai, Annette; Saarela, Janna; Søndergaard, Helle Bach; Spurkland, Anne; Taylor, Bruce; Winkelmann, Juliane; Zipp, Frauke; Haines, Jonathan L; Pericak-Vance, Margaret A; Spencer, Chris C A; Stewart, Graeme; Hafler, David A; Ivinson, Adrian J; Harbo, Hanne F; Hauser, Stephen L; De Jager, Philip L; Compston, Alastair; McCauley, Jacob L; Sawcer, Stephen; McVean, Gil

2016-01-01

Association studies have greatly refined the understanding of how variation within the human leukocyte antigen (HLA) genes influences risk of multiple sclerosis. However, the extent to which major effects are modulated by interactions is poorly characterized. We analyzed high-density SNP data on 17,465 cases and 30,385 controls from 11 cohorts of European ancestry, in combination with imputation of classical HLA alleles, to build a high-resolution map of HLA genetic risk and assess the evidence for interactions involving classical HLA alleles. Among new and previously identified class II risk alleles (HLA-DRB1*15:01, HLA-DRB1*13:03, HLA-DRB1*03:01, HLA-DRB1*08:01 and HLA-DQB1*03:02) and class I protective alleles (HLA-A*02:01, HLA-B*44:02, HLA-B*38:01 and HLA-B*55:01), we find evidence for two interactions involving pairs of class II alleles: HLA-DQA1*01:01–HLA-DRB1*15:01 and HLA-DQB1*03:01–HLA-DQB1*03:02. We find no evidence for interactions between classical HLA alleles and non-HLA risk-associated variants and estimate a minimal effect of polygenic epistasis in modulating major risk alleles. PMID:26343388

DQB1*06:02 allele-specific expression varies by allelic dosage, not narcolepsy status

DEFF Research Database (Denmark)

Weiner Lachmi, Karin; Lin, Ling; Kornum, Birgitte Rahbek

2012-01-01

The association of narcolepsy-cataplexy, a sleep disorder caused by the loss of hypocretin/orexin neurons in the hypothalamus, with DQA1*01:02-DQB1*06:02 is one of the tightest known single-allele human leukocyte antigen (HLA) associations. In this study, we explored genome-wide expression...

Distribution of HLA-DRB1/DQB1 alleles and DRB1-DQB1 ...

African Journals Online (AJOL)

Marwa Chaouali

2017-03-17

Mar 17, 2017 ... Background: Autoimmune hepatitis (AIH) is a chronic inflammatory disease characterized by necrotic inflammation leading to hepatocyte destruction. The association of human leukocyte antigens (HLA) with. AIH development and onset is not fully elucidated especially in the Tunisian population. Objectives: ...

Association between diabetes type 1 and DQB1 alleles in a case-control study conducted in Montevideo, Uruguay.

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Mimbacas, Adriana; Pérez-Bravo, Francisco; Hidalgo, Pedro C; Javiel, Gerardo; Pisciottano, Carmen; Grignola, Rosario; Jorge, Ana María; Gallino, Juan Pablo; Gasagoite, Jackeline; Cardoso, Horacio

2003-03-31

We studied HLA DQB1 allele frequencies and the relative risk (RR) of various genotypes in 72 type 1 diabetic patients and 40 control individuals in Uruguay. This is a tri-racial (Caucasian, Black and Indo-American) mixed population. The products of the polymerase chain reaction amplifications were hybridized with oligonucleotides by allele-specific oligonucleotide reverse or dot blot methods. Significant differences between these two groups were observed only for allele DQB1*0302 (35%, RR = 7.34, P<0.001). The frequency of the alleles carrying a non-aspartic acid residue at position 57 was significantly higher in the diabetic patients (85 vs 53%, P<0.001). In contrast, the frequency of Asp alleles was negatively associated with type 1 diabetes (RR = 0.20, P<0.001). The genotype DQB1*0302/DQB1*0201 (33%, RR = 5.41, P<0.05) was positively associated with this disease. The genotype frequencies associated with type 1 diabetes in our population were significantly different from what is known for Caucasian and Black populations as well as compared with another admixed population, from Chile.

Associations of anti-beta2-glycoprotein I autoantibodies with HLA class II alleles in three ethnic groups.

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Arnett, F C; Thiagarajan, P; Ahn, C; Reveille, J D

1999-02-01

To determine any HLA associations with anti-beta2-glycoprotein I (anti-beta2GPI) antibodies in a large, retrospectively studied, multiethnic group of 262 patients with primary antiphospholipid antibody syndrome (APS), systemic lupus erythematosus (SLE), or another connective tissue disease. Anti-beta2GPI antibodies were detected in sera using an enzyme-linked immunosorbent assay. HLA class II alleles (DRB1, DQA1, and DQB1) were determined by DNA oligotyping. The HLA-DQB1*0302 (DQ8) allele, typically carried on HLA-DR4 haplotypes, was associated with anti-beta2GPI when compared with both anti-beta2GPI-negative SLE patients and ethnically matched normal controls, especially in Mexican Americans and, to a lesser extent, in whites. Similarly, when ethnic groups were combined, HLA-DQB1*0302, as well as HLA-DQB1*03 alleles overall (DQB1*0301, *0302, and *0303), were strongly correlated with anti-beta2GPI antibodies. The HLA-DR6 (DR13) haplotype DRB1*1302; DQB1*0604/5 was also significantly increased, primarily in blacks. HLA-DR7 was not significantly increased in any of these 3 ethnic groups, and HLA-DR53 (DRB4*0101) was increased in Mexican Americans only. Certain HLA class II haplotypes genetically influence the expression of antibodies to beta2GPI, an important autoimmune response in the APS, but there are variations in HLA associations among different ethnic groups.

HLA Class II Allele, Haplotype, and Genotype Associations with Type 1 Diabetes in Benin: A Pilot Study

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Kaossarath A. Fagbemi

2017-01-01

Full Text Available Background. Several studies have reported the implication of HLA-DR/DQ loci in the susceptibility to type 1 diabetes (T1D. Since no such study has yet been performed in Benin, this pilot one aimed at assessing HLA class II allele, haplotype, and genotype associations with T1D. Material and Methods. Class II HLA genotyping was performed in 51 patients with T1D and 51 healthy unrelated controls by means of the PCR-SSP method. The diagnosis of T1D was set up according to American Diabetes Association criteria. Odds ratio (OR and its 95% confidence interval (95% CI were calculated to assess the associations between T1D and HLA alleles, haplotypes, and genotypes. Results. Participants were aged 1–24 years. T1D was significantly associated with DR3, DQA1∗05:01, DQB1∗02:01, and DR3-DR4. No significant associations were observed with DR4, DQB1∗03:02, and DQB1∗06:02. Conclusion. Certain HLA class II alleles, haplotypes, and genotypes were related to T1D and may be used as genetic susceptibility markers to T1D in Benin.

HLA genetic profile of Mapuche (Araucanian) Amerindians from Chile.

Science.gov (United States)

Rey, Diego; Parga-Lozano, Carlos; Moscoso, Juan; Areces, Cristina; Enriquez-de-Salamanca, Mercedes; Fernández-Honrado, Mercedes; Abd-El-Fatah-Khalil, Sedeka; Alonso-Rubio, Javier; Arnaiz-Villena, Antonio

2013-07-01

Amerindian Mapuche (Araucanians) are now living in Chile and Argentina at both sides of Andean Mountains. They are anthropologically and genetically different from southernmost South America Patagonian Amerindians. Most of the HLA alleles found in our Mapuche sample are frequent or very frequent in North and South America Amerindians: (1) Class I: A*02:01, A*03:01, A*68:01, B*39:09, B*51:01, (2) Class II: DRB1*03:01, DRB1*04:03, DRB1*07:01, DRB1*08:02, DRB1*14:02, DRB1*16:02. One of the nine most frequent extended haplotypes seems to be from European origin, suggesting the existence of a degree of admixture with Europeans in our Mapuche sample. It has been calculated of about 11 % admixture. Three of the extended haplotypes are also found in other Amerindians and five of them are newly found in Mapuche Amerindians: A*68:01-B*39:09-DRB1*08:02-DQB1*04:02; A*68:01-B*51:01-DRB1*04:03-DQB1*03:02; A*29:01-B*08:01-DRB1*03:01-DQB1*02:01; A*02:01-B*15:01-DRB1*04:03-DQB1*03:02; A*33:01-B*14:02-DRB1*07:01-DQB1*03:03. The medical importance of calculating HLA profile is discussed on the diagnostic (HLA and disease) and therapeutical bases of HLA pharmacogenomics and on the construction of a virtual transplantation HLA list profile. Also, anthropological conclusions are drawn.

Autoimmunity predominates in a large South African cohort with Addison's disease of mainly European descent despite long-standing disease and is associated with HLA DQB*0201.

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Ross, Ian; Boulle, Andrew; Soule, Steven; Levitt, Naomi; Pirie, Fraser; Karlsson, Anders; Mienie, Japie; Yang, Ping; Wang, Hongjie; She, Jin-Xiong; Winter, William; Schatz, Desmond

2010-09-01

We sought to determine whether autoimmunity is the predominant cause of Addison's disease in South Africa and whether human leucocyte antigen (HLA) DQ association exists. We compiled a national registry of patients from primary care, referral centres and private practices. A total of 144 patients, 94 of European descent, 34 Mixed Ancestry, 5 Asian and 11 Black Africans (mean age 45.9 years, range 2.7-88 years; mean duration of disease 13.1 years, range 0-50 years) and controls were matched for gender and ethnicity. All potential causes were investigated. Fifty one per cent of cases (74 patients) were autoimmune in aetiology. Either 21-hydroxylase autoantibodies (72 patients, 50% of entire patient group) or adrenocortical autoantibodies (35 patients, 24%) were present, while 23% of patients had both. None of the Asian (n = 5) or Black (n = 11) patients had evidence of autoimmune disease. Overall 8% of patients had tuberculosis, 4% adrenoleucodystrophy, 1% adrenocorticotrophic hormone resistance syndrome and 6% X-linked adrenal hypoplasia. In those with autoimmune disease primary hypothyroidism (47%), premature ovarian failure (8%) and type 1 diabetes (7%) were the most prevalent accompanying autoimmune conditions. HLA DQB1*0201 alleles predominated in the autoimmune group (DQB1*0201: 65%vs 43% of controls P = 0.017) with the *0201/*0302 heterozygous genotype being the most prevalent (28%vs 8%P = 0.02). While autoimmunity accounts for at least half of patients with Addison's disease in South Africa and is associated with HLA DQB1*0201, none of the Black Africans or Asians in this cohort had adrenal autoantibodies. Moreover, 21-hydroxylase autoantibodies were detectable in a higher proportion than adrenocortical autoantibodies, especially in those patients with a long history after disease onset.

Distinct HLA associations of LGI1 and CASPR2-antibody diseases.

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Binks, Sophie; Varley, James; Lee, Wanseon; Makuch, Mateusz; Elliott, Katherine; Gelfand, Jeffrey M; Jacob, Saiju; Leite, M Isabel; Maddison, Paul; Chen, Mian; Geschwind, Michael D; Grant, Eleanor; Sen, Arjune; Waters, Patrick; McCormack, Mark; Cavalleri, Gianpiero L; Barnardo, Martin; Knight, Julian C; Irani, Sarosh R

2018-05-18

The recent biochemical distinction between antibodies against leucine-rich, glioma-inactivated-1 (LGI1), contactin-associated protein-2 (CASPR2) and intracellular epitopes of voltage-gated potassium-channels (VGKCs) demands aetiological explanations. Given established associations between human leucocyte antigen (HLA) alleles and adverse drug reactions, and our clinical observation of frequent adverse drugs reactions in patients with LGI1 antibodies, we compared HLA alleles between healthy controls (n = 5553) and 111 Caucasian patients with VGKC-complex autoantibodies. In patients with LGI1 antibodies (n = 68), HLA-DRB1*07:01 was strongly represented [odds ratio = 27.6 (95% confidence interval 12.9-72.2), P = 4.1 × 10-26]. In contrast, patients with CASPR2 antibodies (n = 31) showed over-representation of HLA-DRB1*11:01 [odds ratio = 9.4 (95% confidence interval 4.6-19.3), P = 5.7 × 10-6]. Other allelic associations for patients with LGI1 antibodies reflected linkage, and significant haplotypic associations included HLA-DRB1*07:01-DQA1*02:01-DQB1*02:02, by comparison to DRB1*11:01-DQA1*05:01-DQB1*03:01 in CASPR2-antibody patients. Conditional analysis in LGI1-antibody patients resolved further independent class I and II associations. By comparison, patients with both LGI1 and CASPR2 antibodies (n = 3) carried yet another complement of HLA variants, and patients with intracellular VGKC antibodies (n = 9) lacked significant HLA associations. Within LGI1- or CASPR2-antibody patients, HLA associations did not correlate with clinical features. In silico predictions identified unique CASPR2- and LGI1-derived peptides potentially presented by the respective over-represented HLA molecules. These highly significant HLA associations dichotomize the underlying immunology in patients with LGI1 or CASPR2 antibodies, and inform T cell specificities and cellular interactions at disease initiation.

HLA-DQBl*0402 alleles polymorphisms detected in Javanese HIV patients with positive anti-Toxoplasma gondii IgM

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Sari, Yulia; Haryati, Sri; Prasetyo, Afiono Agung; Hartono, Adnan, Zainal Arifin

2017-02-01

The human leukocyte antigen (HLA)-DQB1 gene polymorphisms may associated with the infection risk of Toxoplasma gondii in HIV patients. The HLA-DQB1*0402 in HIV-1-positive patients could be considered risk factors for developing neurological opportunistic infections, mainly Toxoplasma encephalitis. However, the HLA-DQB1*0402 gene polymorphisms status in the Javanese HIV patients is unknown. This study evaluated the prevalence of HLA-DQB*0402 alleles polymorphisms in Javanese HIV patients with positive anti-Toxoplasma gondii IgM status. Since 2009 our research group performing a molecular epidemiology of blood borne viruses in Central Java Indonesia, by collecting the epidemiological and clinical data from the high risk communities. All blood samples were screened for blood borne pathogens by serological and molecular assays including for HIV and Toxoplasma gondii. The genomic DNA was isolated from the whole blood samples. Genetic polymorphisms of HLA-DQB1*0402 alleles were detected with polymerase chain reaction-sequence-specific primers (PCR-SSPs) technique. The genotypes were defined according to generated fragment patterns in the agarose gel electrophoresis analysis of PCR products. All of the samples were tested at least in duplicate. HLA-DQB1*0402 alleles were detected in 20.8% (16/77) patients and not detected in all HIV positive samples with negative anti-Toxoplasma gondii IgM status (n= 200). The HLA-DQB1*0402 alleles polymorphisms were detected in Javanese HIV patients with positive anti-Toxoplasma gondii IgM. The polymorphisms found may have association with the infection risk of Toxoplasma gondii in HIV patients.

HLA class II polymorphism and IDDM susceptibility in the Greek population.

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Khalil, I; Spyropoulou, M; Mallet, C; Loste, M N; Douay, C; Laperrière, J; Bartzokas, C; Lepage, V; Charron, D; Stavropoulos, C

1993-06-01

The frequencies of HLA-DQA1, DQB1 and DRB1 alleles were compared between 50 Insulin-Dependent Diabetes Melitus (IDDM) patients and 49 healthy controls in the Greek population. Statistically significant difference in the frequencies of HLA-DQA1*0501-DQB1*0201 (P = 10(-4)), DQA1*0301-DQB1*0201 (P = 0.01) and DQA1*0301-DQB1*0302 (P = 0.001) were observed. The DRB1*0405-DQA1*0301-DQB1*0201 was the only DR, DQ combination significantly associated with the disease. The unexpected increase of DRB1*0405 observed in the Greek IDDM may suggest as reported in Chinese and Japanese IDDM a contribution of DR beta and DQ alpha in susceptibility. Moreover, in contrast to the Asians, in the Greek, the DR beta, DQ alpha are found with the usual DQ beta 57-ve.

Multiple Sclerosis Risk Variant HLA-DRB1*1501 Associates with High Expression of DRB1 Gene in Different Human Populations

Science.gov (United States)

Abad-Grau, María del Mar; Fedetz, María; Izquierdo, Guillermo; Lucas, Miguel; Fernández, Óscar; Ndagire, Dorothy; Catalá-Rabasa, Antonio; Ruiz, Agustín; Gayán, Javier; Delgado, Concepción; Arnal, Carmen

2012-01-01

The human leukocyte antigen (HLA) DRB1*1501 has been consistently associated with multiple sclerosis (MS) in nearly all populations tested. This points to a specific antigen presentation as the pathogenic mechanism though this does not fully explain the disease association. The identification of expression quantitative trait loci (eQTL) for genes in the HLA locus poses the question of the role of gene expression in MS susceptibility. We analyzed the eQTLs in the HLA region with respect to MS-associated HLA-variants obtained from genome-wide association studies (GWAS). We found that the Tag of DRB1*1501, rs3135388 A allele, correlated with high expression of DRB1, DRB5 and DQB1 genes in a Caucasian population. In quantitative terms, the MS-risk AA genotype carriers of rs3135388 were associated with 15.7-, 5.2- and 8.3-fold higher expression of DQB1, DRB5 and DRB1, respectively, than the non-risk GG carriers. The haplotype analysis of expression-associated variants in a Spanish MS cohort revealed that high expression of DRB1 and DQB1 alone did not contribute to the disease. However, in Caucasian, Asian and African American populations, the DRB1*1501 allele was always highly expressed. In other immune related diseases such as type 1 diabetes, inflammatory bowel disease, ulcerative colitis, asthma and IgA deficiency, the best GWAS-associated HLA SNPs were also eQTLs for different HLA Class II genes. Our data suggest that the DR/DQ expression levels, together with specific structural properties of alleles, seem to be the causal effect in MS and in other immunopathologies rather than specific antigen presentation alone. PMID:22253788

HLA similarities indicate shared genetic risk in 21-hydroxylase autoantibody positive South African and United States Addison's disease.

Science.gov (United States)

Ross, I L; Babu, S; Armstrong, T; Zhang, L; Schatz, D; Pugliese, A; Eisenbarth, G; Baker Ii, P

2014-10-01

Genetic similarities between patients from the United States and South African (SA) Addison's Disease (AD) strengthen evidence for genetic association. SA-AD (n = 73), SA healthy controls (N = 78), and US-AD patients (N = 83) were genotyped for DQA1, DQB1, DRB1, and HLA-B alleles. Serum was tested for the quantity of 21OH-AA and IFNα-AA at the Barbara Davis Center. Although not as profound as in US-AD, in SA-AD 21OH-AA + subjects the predominantly associated risk haplotypes were DRB1*0301-DQB1*0201 (DR3), DRB1*04xx-DQB1*0302 (DR4), and the combined DR3/4 genotype. DQB1*0302 associated DRB1*04xx haplotypes conferred higher risk than those DRB1*04xx haplotypes associated with other DQB1 alleles. We found negative association in 21OH-AA + SA-AD for DQA1*0201-DQB1*0202 and DQA1*0101-DQB1*0501 vs SA controls, and positive association for DQA1*0401-DQB1*0402 vs US-AD. Apart from the class II DR3 haplotype, HLA-B8 did not have an independent effect; however together DR3 and HLA-B8 conferred the highest risk vs 21OH-AA negative SA-AD and SA-controls. HLA-B7 (often with DR4) conferred novel risk in 21OH-AA + SA-AD vs controls. This study represents the first comparison between South African and United States AD populations utilizing genotyping and serology performed at the same center. SA-AD and US-AD 21OH-AA + patients share common HLA risk haplotypes including DR4 (with HLA-B7) and DR3 (with HLA-B8), strengthening previously described HLA associations and implicating similar genetic etiology. © 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Association of gliadin antibodies, HLA alleles, and schizophrenia in Cuban population patients

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José A. Galván

2016-05-01

Full Text Available Introduction: Several lines of evidence have suggested an interesting link between gluten ingestion and schizophrenia. For example, increased levels of gliadin and transglutaminase antibodies have been observed in patients with schizophrenia. Methods: To verify these observations we compared the prevalence of gliadin and transglutaminse antibodies, as well as the presence of the HLA alleles, HLA DQA1*0501-DQB1*02 (DQ2 and HLA-DQA1*0301-DQB1*0302 (DQ8, among patients with schizophrenia and healthy controls. A total of 108 patients with schizophrenia and 60 healthy controls were evaluated. Gliadin antibodies were determined by a visual semiquantitative assay and tissue transglutaminase antibodies were determined both by one-step immunochromatografic assay and ELISA. HLA typing was performed by PCR amplification using sequence-specific primers for each allele. Results: We found a strong association between the presence of gliadin antibodies and schizophrenia (OR 3.488; 95% CI, 1.43-8.44. However, tissue transglutaminase antibodies were not detected in either group neither by immunochromatograpic or ELISA. No significant association was found for the DQ2 or DQ8 heterodimer and the disease, but a significant positive association between schizophrenia and HLA alleles DQA1*0301 and DQB1*02 was present (OR = 2.80; 95% CI, 1.27-6.17, and OR = 2.37, 95% CI, 1.24-4.53, respectively. Conclusions: The present study showed that the presence of gliadin antibodies was not correlated with the presence of HLA DQA1*0301 or DQB1*02 alleles within the group of patients with schizophrenia. Our study replicates the findings that anti-gliadin antibodies are associated with schizophrenia but also suggests that the presence of these antibodies and the HLA alleles DQB1*02 and DQA1*0301 are independently associated with susceptibility to schizophrenia.

Multiple sclerosis risk variant HLA-DRB1*1501 associates with high expression of DRB1 gene in different human populations.

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Antonio Alcina

Full Text Available The human leukocyte antigen (HLA DRB1*1501 has been consistently associated with multiple sclerosis (MS in nearly all populations tested. This points to a specific antigen presentation as the pathogenic mechanism though this does not fully explain the disease association. The identification of expression quantitative trait loci (eQTL for genes in the HLA locus poses the question of the role of gene expression in MS susceptibility. We analyzed the eQTLs in the HLA region with respect to MS-associated HLA-variants obtained from genome-wide association studies (GWAS. We found that the Tag of DRB1*1501, rs3135388 A allele, correlated with high expression of DRB1, DRB5 and DQB1 genes in a Caucasian population. In quantitative terms, the MS-risk AA genotype carriers of rs3135388 were associated with 15.7-, 5.2- and 8.3-fold higher expression of DQB1, DRB5 and DRB1, respectively, than the non-risk GG carriers. The haplotype analysis of expression-associated variants in a Spanish MS cohort revealed that high expression of DRB1 and DQB1 alone did not contribute to the disease. However, in Caucasian, Asian and African American populations, the DRB1*1501 allele was always highly expressed. In other immune related diseases such as type 1 diabetes, inflammatory bowel disease, ulcerative colitis, asthma and IgA deficiency, the best GWAS-associated HLA SNPs were also eQTLs for different HLA Class II genes. Our data suggest that the DR/DQ expression levels, together with specific structural properties of alleles, seem to be the causal effect in MS and in other immunopathologies rather than specific antigen presentation alone.

Allorecognition of HLA-C mismatches by CD8+ T cells in hematopoietic stem cell transplantation is a complex interplay between mismatched peptide binding region residues, HLA-C expression and HLA-DPB1 disparities

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Florence Bettens

2016-12-01

Full Text Available HLA-C locus mismatches are the most frequent class I disparities in unrelated hematopoietic stem cell transplantation (HSCT and have a detrimental impact on clinical outcome. Recently, a few retrospective clinical studies have reported some variability in the immunogenicity of HLA-C incompatibilities. To get better insight into presumably permissive HLA-C mismatches we have developed a one-way in vitro mixed lymphocyte reaction (MLR assay allowing to quantify activated CD56-CD137+CD8+ lymphocytes in HLA-C incompatible combinations. T cell-mediated alloresponses were correlated with genetic markers such as HLA-C mRNA expression and the number of amino acid mismatches in the α1/α2 domains (peptide binding region. Because of the high rate of HLA-DPB1 incompatibilities in HLA-A, B, C, DRB1 and DQB1 matched unrelated HSCT patient/donor pairs, the impact of HLA-DPB1 mismatching, a potential bystander of CD4+ T cell activation, was also considered. Heterogeneous alloresponses were measured in 63 HLA-C mismatched pairs with a positive assay in 52% of the combinations (2.3-18.6% activated CTLs, representing 24 different HLA-A~B~DRB1~DQB1 haplotypes. There was no correlation between measured alloresponses and mRNA expression of the mismatched HLA-C alleles. The HLA-C*03:03/03:04 mismatch did not induce any positive alloresponse in 5 MLRs. We also identified HLA-C*02:02 and HLA-C*06:02 as mismatched alleles with lower immunogenicity, and HLA-C*14:02 as a more immunogenic mismatch. A difference of at least 10 amino acid residues known to impact peptide/TCR binding and a bystander HLA-DPB1 incompatibility had a significant impact on CTL alloreactivity (p=0.021. The same HLA-C mismatch, when recognized by two different responders with the same HLA haplotypes, was recognized differently, emphasizing the role of the T-cell repertoire of responding cells. In conclusion, mismatched HLA-C alleles differing by10 or more amino acids in the peptide/TCR binding

The immunogenetics of multiple sclerosis. The frequency of HLA-alleles class 1 and 2 is lower in Southern Brazil than in the European population.

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Werneck, Lineu Cesar; Lorenzoni, Paulo José; Arndt, Raquel Cristina; Kay, Cláudia Suemi Kamoi; Scola, Rosana Herminia

2016-08-01

To study the HLA of class 1and 2 in a multiple sclerosis (MS) population to verify the susceptibility for the disease in the Southern Brazil. We analyzed patients with MS and controls, by direct sequencing of the genes related to HLA DRB1, DQB1, DPB1, A, B and C alleles with high resolution techniques. We found a lower frequency of all HLA alleles class 1 and 2 in MS and controls comparing to the European population. Several alleles had statistical correlation, but after Bonferroni correction, the only allele with significance was the HLA-DQB1*02:03, which has a positive association with MS. Our data have different frequency of HLA-alleles than the previous published papers in the Southeast Brazil and European population, possible due to several ethnic backgrounds.

A polymorphism in the HLA-DPB1 gene is associated with susceptibility to multiple sclerosis.

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Judith Field

2010-10-01

Full Text Available We conducted an association study across the human leukocyte antigen (HLA complex to identify loci associated with multiple sclerosis (MS. Comparing 1927 SNPs in 1618 MS cases and 3413 controls of European ancestry, we identified seven SNPs that were independently associated with MS conditional on the others (each P ≤ 4 x 10(-6. All associations were significant in an independent replication cohort of 2212 cases and 2251 controls (P ≤ 0.001 and were highly significant in the combined dataset (P ≤ 6 x 10(-8. The associated SNPs included proxies for HLA-DRB1*15:01 and HLA-DRB1*03:01, and SNPs in moderate linkage disequilibrium (LD with HLA-A*02:01, HLA-DRB1*04:01 and HLA-DRB1*13:03. We also found a strong association with rs9277535 in the class II gene HLA-DPB1 (discovery set P = 9 x 10(-9, replication set P = 7 x 10(-4, combined P = 2 x 10(-10. HLA-DPB1 is located centromeric of the more commonly typed class II genes HLA-DRB1, -DQA1 and -DQB1. It is separated from these genes by a recombination hotspot, and the association is not affected by conditioning on genotypes at DRB1, DQA1 and DQB1. Hence rs9277535 represents an independent MS-susceptibility locus of genome-wide significance. It is correlated with the HLA-DPB1*03:01 allele, which has been implicated previously in MS in smaller studies. Further genotyping in large datasets is required to confirm and resolve this association.

HLA alleles and HLA-B27 haplotypes associated with susceptibility and severity of ankylosing spondylitis in a Portuguese population.

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Pimentel-Santos, F M; Matos, M; Ligeiro, D; Mourão, A F; Ribeiro, C; Costa, J; Santos, H; Barcelos, A; Pinto, P; Cruz, M; Sousa, E; Santos, R A; Fonseca, J E; Trindade, H; Guedes-Pinto, H; Branco, J C

2013-12-01

Human leukocyte antigen (HLA)-B27 is the mostly known major histocompatibility complex (MHC) gene associated with ankylosing spondylitis (AS). Nonetheless, there is substantial evidence that other MHC genes appear to be associated with the disease, although it has not yet been established whether these associations are driven by direct associations or by linkage disequilibrium (LD) mechanisms. We aimed to investigate the contributions of HLA class I and II alleles and B27-haplotypes for AS in a case-control study. A total of 188 HLA-B27 AS cases and 189 HLA-B27 healthy controls were selected and typed for HLA class I and II by the Luminex polymerase chain reaction-sequence specific oligonucleotide probe (PCR-SSOP) method. Allelic and haplotypic distributions were estimated by maximum likelihood method using Arlequin v3.11 and statistical analysis were performed by Stata10.1. No associations were found between non-HLA-B27 loci and AS susceptibility, but several associations were observed for phenotypic features of the disease. DRB1*08 was identified as a risk factor for uveitis and DQB1*04 seems to provide protection for AS severity (functional, metrological and radiological indexes). A*02/B27/C*02/DRB1*01/DQB1*05 [P<0.0001; odds ratio (OR) = 39.06; 95% confidence interval (CI) (2.34-651)] is the only haplotype that seems to confer susceptibility to AS. Moreover, the haplotype A*02/B27/C*01/DRB1*08/DQB1*04 seems to provide protection for disease functional and radiological repercussions. Our findings are compatible with the hypothesis that other genes within the HLA region besides HLA-B27 might play some role in AS susceptibility and severity. © 2013 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Gradiente de riesgo genético HLA-DQ para diabetes tipo 1 y enfermedad celíaca en el noroeste de México

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Mejía-León, M.E.; Ruiz-Dyck, K.M.; Calderón de la Barca, A.M.

2015-01-01

Antecedentes: La diabetes tipo 1 (DT1) y la enfermedad celíaca (EC) son 2 enfermedades autoinmunes frecuentes en la infancia y comparten su predisposición genética (HLA-DQ2 y DQ8). La prevalencia de ambas se ha incrementado en el mundo. En el estado de Sonora (15 habitantes/km2), se desconoce información sobre su riesgo genético o la distribución de los alelos asociados en la población general. Objetivo: Comparar la frecuencia alélica HLA-DQ de una muestra representativa de recién nacidos ...

The Clinical Course of Patients with Preschool Manifestation of Type 1 Diabetes Is Independent of the HLA DR-DQ Genotype

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Christina Reinauer

2017-05-01

Full Text Available Introduction: Major histocompatibility complex class II genes are considered major genetic risk factors for autoimmune diabetes. We analysed Human Leukocyte Antigen (HLA DR and DQ haplotypes in a cohort with early-onset (age < 5 years, long term type 1 diabetes (T1D and explored their influence on clinical and laboratory parameters. Methods: Intermediate resolution HLA-DRB1, DQA1 and DQB1 typing was performed in 233 samples from the German Paediatric Diabetes Biobank and compared with a local control cohort of 19,544 cases. Clinical follow-up data of 195 patients (diabetes duration 14.2 ± 2.9 years and residual C-peptide levels were compared between three HLA risk groups using multiple linear regression analysis. Results: Genetic variability was low, 44.6% (104/233 of early-onset T1D patients carried the highest-risk genotype HLA-DRB1*03:01-DQA1*05:01-DQB1*02:01/DRB1*04-DQA1*03:01-DQB1*03:02 (HLA-DRB1*04 denoting 04:01/02/04/05, and 231 of 233 individuals carried at least one of six risk haplotypes. Comparing clinical data between the highest (n = 83, moderate (n = 106 and low risk (n = 6 genotypes, we found no difference in age at diagnosis (mean age 2.8 ± 1.1 vs. 2.8 ± 1.2 vs. 3.2 ± 1.5 years, metabolic control, or frequency of associated autoimmune diseases between HLA risk groups (each p > 0.05. Residual C-peptide was detectable in 23.5% and C-peptide levels in the highest-risk group were comparable to levels in moderate to high risk genotypes. Conclusion: In this study, we saw no evidence for a different clinical course of early-onset T1D based on the HLA genotype within the first ten years after manifestation.

Comparison of allele frequency for HLA-DR and HLA-DQ between patients with ECC and caries-free children

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Bagherian A

2008-03-01

Full Text Available Background: Early childhood caries (ECC is one of the most common diseases of childhood. The etiology of ECC is multifactorial and both genetic and environmental factors play important roles in the pathogenesis of the disease. Genetic variations in the hosts may contribute to changes in the risk for dental caries. Genetic factors such as human leukocyte antigen (HLA have recently been suggested as a predisposing factor. Aim: The aim of this study was to look for an association between HLA-DRB1 and HLA-DQB1 with ECC for developing new strategies for the diagnosis as well as the prevention of the disease. Design: In this study, we extracted the genomic DNAs from whole blood samples of 44 patients with ECC and 35 caries-free children by the salting-out method. We amplified the genomic DNA by PCR-SSP and then HLA-typing was performed for all alleles. Results: The results revealed a significant increase in the frequency of HLA-DRB1FNx0104 in the patient group (P = 0.019. The odds ratio for this allele was detected to be 10. The frequency of HLA-DQB1 alleles was not significantly different between the two groups. Conclusion: The above results suggest that HLA-DRB1FNx0104 is associated with the susceptibility to ECC. Thus HLA-DRB1FNx0104 detection as a molecular marker for early diagnosis of ECC may be recommended.

Influence of the HLA class II polymorphism in chronic Chagas' disease.

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Fernandez-Mestre, M T; Layrisse, Z; Montagnani, S; Acquatella, H; Catalioti, F; Matos, M; Balbas, O; Makhatadze, N; Dominguez, E; Herrera, F; Madrigal, A

1998-04-01

Chagas' disease or American trypanosomiasis due to Trypanosoma cruzi has existed at least since the time of the Inca empire and contributes significantly to cardiovascular morbidity and mortality in several countries of this continent. Due to the fundamental role of human class II molecules polymorphic residues in the control of the immune response, a study was designed to define by DNA typing HLA class II alleles in a sample of 67 serologically positive individuals with and without cardiomyopathy and in 156 healthy controls of similar ethnic origin. Genomic DNA extraction, PCR amplification of the HLA-DRB1 and DQB1 second exon regions and hybridization to labelled specific probes were carried out following the 11th International Histocompatibility Workshop reference protocol. Comparison of DRB1 and DQB1 allele frequencies among the patients and control subjects showed a decreased frequency of DRB1*14 and DQB1*0303 in the patients, suggesting independent protective effects to the chronic infection in this population. Allele frequencies comparison between patients with and without cardiomyopathy showed a higher frequency of DRB1*01, DRB1*08 and DQB1*0501 and a decreased frequency of DRB1*1501 in the patients with arrhythmia and congestive heart failure. The results suggest that HLA Class II genes may be associated with the development of a chronic infection and with heart damage in Chagas' disease.

Molecular typing of HLA class II antigens in a São Paulo population

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Goldberg A.C.

1998-01-01

Full Text Available In the present paper we show data obtained from a normal population with a racially mixed profile typical of the city of São Paulo, State of São Paulo. Data were generated with polymerase chain reaction using sequence specific primers (PCR-SSP for HLA-DRB and polymerase chain reaction followed by hybridization with sequence specific oligonucleotide probes (PCR-SSO for HLA-DQA1 and HLA-DQB1 loci. HLA-DRB, DQA1, DQB1 and haplotype frequencies as well as common linkage disequilibria were found. This population was also shown to be in genetic equilibrium according to the Hardy-Weinberg law. HLA-DR typing of a normal sample from the city of Porto Velho, State of Rondonia, highlighted the importance of different sets of HLA profiles found in other regions of the country. This database provides essential information for screening studies of disease associations, forensic analyses and transplants.

HLA Class I and Class II Alleles and Haplotypes Confirm the Berber Origin of the Present Day Tunisian Population.

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Abdelhafidh Hajjej

Full Text Available In view of its distinct geographical location and relatively small area, Tunisia witnessed the presence of many civilizations and ethnic groups throughout history, thereby questioning the origin of present-day Tunisian population. We investigated HLA class I and class II gene profiles in Tunisians, and compared this profile with those of Mediterranean and Sub-Sahara African populations. A total of 376 unrelated Tunisian individuals of both genders were genotyped for HLA class I (A, B and class II (DRB1, DQB1, using reverse dot-blot hybridization (PCR-SSO method. Statistical analysis was performed using Arlequin software. Phylogenetic trees were constructed by DISPAN software, and correspondence analysis was carried out by VISTA software. One hundred fifty-three HLA alleles were identified in the studied sample, which comprised 41, 50, 40 and 22 alleles at HLA-A,-B,-DRB1 and -DQB1 loci, respectively. The most frequent alleles were HLA-A*02:01 (16.76%, HLA-B*44:02/03 (17.82%, HLA-DRB1*07:01 (19.02%, and HLA-DQB1*03:01 (17.95%. Four-locus haplotype analysis identified HLA-A*02:01-B*50:01-DRB1*07:01-DQB1*02:02 (2.2% as the common haplotype in Tunisians. Compared to other nearby populations, Tunisians appear to be genetically related to Western Mediterranean population, in particular North Africans and Berbers. In conclusion, HLA genotype results indicate that Tunisians are related to present-day North Africans, Berbers and to Iberians, but not to Eastern Arabs (Palestinians, Jordanians and Lebanese. This suggests that the genetic contribution of Arab invasion of 7th-11th century A.D. had little impact of the North African gene pool.

Association of HLA-DQ trans-heterodimers with prevalence of type 1 diabetes mellitus in Buryat ethnic group

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Olga Nikolaevna Ivanova

2012-09-01

Full Text Available Aims. Search for the most pronounced HLA II markers of type 1 diabetes mellitus (T1DM in Buryat ethnic group and analysis ofHLA-DQ trans-heterodimers. Materials and methods. Case control design was applied for assessment of 74 patients with T1DM and 61 healthy individuals. Alleleidentification was performed with multi-primer allele-specific PCR technique. Association of genetic markers with pathology wasevaluated according to odds ratio (OR index. All calculations were performed with StatSoft and STATISTICA 6 software applications. Results. We show that regarding race-specific highly diabetogenic HLA class II haplotypes Buryat ethnic group holds intermediateposition between Mongoloids and Caucasians and none of those haplotypes are associated with T1DM. We revealed a statisticallysignificant association of T1DM with DQA1*0301+DQB1*0201+ phenotype represented by trans-coding alleles in 77% of cases. Onpopulation level DQA1*0301+DQB1*0302+ or *0201+ phenotype is found to be the most sensitive marker. It was registered in 43%of patients with T1DM against 11.5% of controls (OR 5.9; рс=0.0094. DQA1*0301+/DQВ1*0201 and DQВ1*0302 phenotype is themost specific marker, registered in 16% of patients, but not found in controls (OR 11.8; рс=0.047.Conclusions. HLA-mediated risk for development of T1DM in Buryat ethnic group is determined by HLA-DQ trans-heterodimers.

HLA Alleles are Genetic Markers for Susceptibility and Resistance towards Leprosy in a Mexican Mestizo Population.

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Aguilar-Medina, Maribel; Escamilla-Tilch, Monica; Frías-Castro, Luis Octavio; Romero-Quintana, Geovanni; Estrada-García, Iris; Estrada-Parra, Sergio; Granados, Julio; Arambula Meraz, Eliakym; Sánchez-Schmitz, Guzman; Khader, Shabaana Abdul; Rangel-Moreno, Javier; Ramos-Payán, Rosalío

2017-01-01

Despite the use of multidrug therapy, leprosy remains endemic in some countries. The association of several human leucocyte antigen (HLA) alleles and gene polymorphisms with leprosy has been demonstrated in many populations, but the major immune contributors associated to the spectrum of leprosy have not been defined yet. In this study, genotyping of HLA-A, -B, -DR, and -DQ alleles was performed in leprosy patients (n = 113) and control subjects (n = 117) from the region with the highest incidence for the disease in México. The odds of developing leprosy and lepromatous subtype were 2.12- and 2.74-fold higher in carriers of HLA-A*28, and 2.48- and 4.14-fold higher for leprosy and dimorphic subtype in carriers of DQB1*06. Interestingly, DQB1*07 was overrepresented in healthy individuals, compared to patients with leprosy (OR = 0.08) and the lepromatous subtype (OR = 0.06). These results suggest that HLA-A*28 is a marker for predisposition to leprosy and the lepromatous subtype and DQB1*06 to leprosy and the dimorphic subtype, while DQB1*07 might be a resistance marker in this Mestizo population. © 2016 John Wiley & Sons Ltd/University College London.

Genetic factors and multiple sclerosis in the Moroccan population: a role for HLA class II.

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Ouadghiri, S; El Alaoui Toussi, K; Brick, C; Ait Benhaddou, E H; Benseffaj, N; Benomar, A; El Yahyaoui, M; Essakalli, M

2013-12-01

Multiple sclerosis (MS) is an autoimmune inflammatory demyelinating disease of the central nervous system that mainly affects young adults. The association between susceptibility to MS and HLA class II genes, in particular the DRB1*15 allele, has been reported in diverse ethnic groups. The aim of our study was to investigate the distribution of HLA-DRB1* and -DQB1* alleles in Moroccan population and their implication in the susceptibility to the disease. Fifty-seven MS patients were compared to 172 healthy controls unrelated to one another and matched by age, sex and ethnic origin. HLA class II (DRB1* and DQB1*) typing was performed by PCR-SSP and/or Luminex (PCR-SSO). Allelic and haplotypic frequencies, P-values, odds ratio (OR) and 95% confidence interval (CI) were calculated using the software SPSS. A significant increase of DRB1*15 allele frequency (17.6% vs 8.4%, OR=2.67, 95% CI=1.36-5.23, P=0.004) and HLA-DRB1*15-DQB1*06 haplotype (8.8% vs 4.08%, OR=2.78, 95% CI=1.41-5.48, P=0.002) were observed in Moroccan MS patients. No association of the DR15 allele with sex or age at onset was appreciated. Concerning HLA-DQB1* alleles, no significant difference between patients and controls was found. Our results reveal a role for HLA-DRB1*15 allele molecules in the predisposition of Moroccan patients to MS. Although this study should be confirmed on a larger sample size, it analyzes for the first time the possible role of a genetic marker for susceptibility to MS in Moroccan population. Copyright © 2013 Elsevier Masson SAS. All rights reserved.

Association of HLA Genotype and Fulminant Type 1 Diabetes in Koreans

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Soo Heon Kwak

2015-12-01

Full Text Available Fulminant type 1 diabetes (T1DM is a distinct subtype of T1DM that is characterized by rapid onset hyperglycemia, ketoacidosis, absolute insulin deficiency, and near normal levels of glycated hemoglobin at initial presentation. Although it has been reported that class II human leukocyte antigen (HLA genotype is associated with fulminant T1DM, the genetic predisposition is not fully understood. In this study we investigated the HLA genotype and haplotype in 11 Korean cases of fulminant T1DM using imputation of whole exome sequencing data and compared its frequencies with 413 participants of the Korean Reference Panel. The HLA-DRB1*04:05–HLA-DQB1*04:01 haplotype was significantly associated with increased risk of fulminant T1DM in Fisher's exact test (odds ratio [OR], 4.11; 95% confidence interval [CI], 1.56 to 10.86; p = 0.009. A histidine residue at HLA-DRβ1 position 13 was marginally associated with increased risk of fulminant T1DM (OR, 2.45; 95% CI ,1.01 to 5.94; p = 0.054. Although we had limited statistical power, we provide evidence that HLA haplotype and amino acid change can be a genetic risk factor of fulminant T1DM in Koreans. Further large-scale research is required to confirm these findings.

Linkage disequilibrium between human leukocyte antigen (HLA) class II and HLA-G--possible implications for human reproduction and autoimmune disease

DEFF Research Database (Denmark)

Hviid, Thomas Vauvert F; Christiansen, Ole B

2005-01-01

). We found a significant linkage disequilibrium between HLA-DR3 and HLA-G*010102 in both the RSA and control populations. For all four studied HLA loci, the alleles in the haplotype HLA-DRB1*03.DQA1*05.DQB1*02.G*010102 was in clear linkage disequilibrium. This HLA haplotype has repeatedly been...... associated with different autoimmune diseases but also with RSA. The G*010102 allele includes a 14-bp sequence polymorphism in the 3' untranslated region of the gene, which has been associated with differences in HLA-G mRNA alternative splicing and stability. This 14-bp polymorphism has also been associated...... with RSA, pre-eclampsia, and outcome of in vitro fertilization. Implications of HLA polymorphism--and other polymorphic genes in the MHC for pregnancy outcome--and for autoimmune diseases during pregnancy are discussed....

[HLA genetic markers and auto-antibody profile in a Mapuche family with a case affected of type 1 diabetes].

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Asenjo, Sylvia; Gleisner, Andrea; Pérez, Francisco

2004-01-01

Type 1 diabetes (DM1) is caused by an autoimmune process that destroys beta cells of pancreas. Not all carriers of susceptible HLA genes and positive for autoantibodies develop the disease. Environmental factors play a role in triggering the autoimmune process. To analyze an exceptional case of DM1 in a Mapuche family in the context of genetic, immunological and environmental factors. A study of a family with an affected female child was carried out in a Mapuche community in Southern Chile (VIII region). This is an unique and sporadic DM1 case with Mapuche heritage. Nutritional and viral infections data were collected by interview and clinical records. A genetic analysis by PCR was done to detect class I and II HLA genes by reverse dot blot. The proband, her mother and sister had positive islet cell antibodies (ICA). Her father and brother were negative. All thefamily was positive for anti glutamic decarboxylase antibodies (GAD65). All subjects had HLA-DRB1 0407/0407 and HLA-DQB1 0302/0302 alleles. The index case and her father were homozygotes for the HLA-A1:A*68012/A*68012 allele. Mean breastfeeding lapse was 18 months in all children. No evidences for viral infections such as rubella, mumps or measles were found in this family. There was an altered profile of autoantibodies in the family of the index case. All genotypes were comparable with the European population where the diabetogenic combination DR4/DQB1*0302 is the most prevalent. No environmental factors could be incriminated as triggers of the disease.

Frecuencia de alelos HLA de clase I y II en una cohorte de pacientes

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Eliana Patricia Velásquez

2012-03-01

Conclusión. Los alelos HLA-B27, HLA-DRB4*01 y HLA-DQB1*0501 fueron frecuentes en los diferentes subtipos de espondiloartritis y en las manifestaciones clínicas axiales, periféricas y extraarticulares específicas, además de la sacroiliítis radiológica.   DOI: http://dx.doi.org/10.7705/biomedica.v32i1.569

Immunogenetics of rheumatoid arthritis and primary Sjögren's syndrome: DNA polymorphism of HLA class II genes

DEFF Research Database (Denmark)

Morling, Niels; Andersen, V; Fugger, L

1992-01-01

. The frequencies of DNA fragments associated with the following HLA class II genes were increased in RA when compared to normal controls: DRB1*04 (DR4) (relative risk, RR = 7.4, P less than 10(-3), DRB4*0101 (DRw53) (RR = 9.6, P less than 10(-3), DQA1*0301 (RR = 9.6, P less than 10(-3), DQB1*0301 (DQw7) (RR = 2.......8, P less than 0.05, 'corrected' P greater than 0.05), and DQB1*0302 (DQw8) (RR = 4.5, P less than 10(-2). Negative associations were found between RA and DRB1*1501 (DR2/DRw15) (RR = 0.2, P less than 10(-2) and DQB1*0602 (DQw6) (RR = 0.2, P less than 10(-2), 'corrected' P greater than 0.......05). The frequencies in RA of other HLA class II associated DNA fragments including DPA and DPB and the antigens DPw1-w6 defined by primed lymphocyte stimulation, did not differ significantly from those in controls. In primary SS, the frequency of HLA-B8 was significantly increased (RR = 9.0, P less than 10...

DNA polymorphism of HLA class II genes in primary biliary cirrhosis

DEFF Research Database (Denmark)

Morling, Niels; Dalhoff, K; Fugger, L

1992-01-01

We investigated the DNA restriction fragment length polymorphism of the major histocompatibility complex class II genes: HLA-DRB, -DQA, -DQB, DPA, -DPB, the serologically defined HLA-A, B, C, DR antigens, and the primed lymphocyte typing defined HLA-DP antigens in 23 Danish patients with primary...... than 0.05, 'corrected' P greater than 0.05). No DNA fragments specific for DRB1*0301 (DR3) could be identified. The frequencies in PBC of other genetic markers including DRw8, DRB1*08, HLA-DP antigens, DPA, and DPB genes did not differ significantly from those in controls. The associations between PBC...

The peopling of Madeira Archipelago (Portugal) according to HLA genes.

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Arnaiz-Villena, A; Reguera, R; Ferri, A; Barbolla, L; Abd-El-Fatah-Khalil, S; Bakhtiyarova, N; Millan, P; Moscoso, J; Mafalda, A; Serrano-Vela, J I

2009-02-01

The Madeira-Porto Santo Archipelago was officially colonized in 1420 by Portuguese settlers. Its importance in Columbus' information for the American discovery and for slave traffic across the Atlantic is unquestionable. Thus, a complex peopling may have given rise to a present-day high admixture of ethnicities according to HLA genes. A sample of 173 healthy unrelated Madeirans was analysed and compared with 6986 HLA chromosomes from other worldwide populations. Genetic distances, neighbour-joining dendrograms and correspondence analyses were used for comparisons. Southern European, North African (including Canary Islands), Jewish and Mediterranean typical HLA alleles were found and genetic distances from Madeirans to these populations were the closest ones. In addition A*24-B*65-DRB1*0102-DQB1*0501 and A*68-B*08-DRB1*0301-DQB1*0201 haplotypes were newly found in Madeira and not found in any other population. Jewish-Armenian-Middle East haplotype (A*33-B*65-DRB1*0102-DQB1*0501) is one of the most common haplotypes; this haplotype is also present in Spaniards and North Africans. Quantitatively, Portuguese, North Africans (Algerians), Spaniards and Canary Islanders (in this order) are the most important parental populations to Madeirans. Results are discussed on the basis of the recorded historical peopling which does not show a noticeable African gene input in present-day Madeiran population according to our data; one of the closest related populations found is the Canary Islanders, suggesting that Guanche (Canary Islands first inhabitants) slaves gene flow is still noticed at present, both in Madeira and in Canary Islands populations.

Sequence-based HLA-A, B, C, DP, DQ, and DR typing of 100 Luo infants from the Boro area of Nyanza Province, Kenya.

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Arlehamn, Cecilia S Lindestam; Copin, Richard; Leary, Shay; Mack, Steven J; Phillips, Elizabeth; Mallal, Simon; Sette, Alessandro; Blatner, Gretta; Siefers, Heather; Ernst, Joel D

2017-04-01

One hundred healthy infants enrolled as controls in a tuberculosis vaccine study in Nyanza Province, Kenya provided anonymized samples for DNA sequence-based typing at the HLA-A, -B, -C, -DPB1, -DQA1, -DQB1, -DRB1, and -DRB3/4/5 loci. The purpose of the study was to characterize allele frequencies in the local population, to support studies of T cell immunity against pathogens, including Mycobacterium tuberculosis. There are no detectable deviations from Hardy Weinberg proportions for the HLA-B, -C, -DRB1, -DPB1, -DQA1 and -DQB1 loci. A minor deviation was detected at the HLA-A locus due to an excess of HLA-A*02:02, 29:02, 30:02, and 68:02 homozygotes. The genotype data are available in the Allele Frequencies Net Database under identifier 3393. Copyright © 2017. Published by Elsevier Inc.

The Familial Risk and HLA Susceptibility among Narcolepsy Patients in Hong Kong Chinese

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Chen, Lei; Fong, S.Y.Y.; Lam, Ching W.; Tang, Nelson L.S.; Ng, Margaret H. L.; Li, Albert M.; Ho, C.K.W.; Cheng, Suk-Hang; Lau, Kin-Mang; Wing, Yun Kwok

2007-01-01

Study Objectives: To explore the familial aggregation and HLA susceptibility of narcolepsy in Hong Kong Chinese by objective sleep measurements and HLA typing. Design: Case control design Participants: Twelve narcoleptic probands, 34 first-degree relatives, and 30 healthy controls. Interventions: N/A Measurements and Results: Each subject underwent a standardized nocturnal polysomnogram (PSG), followed by a daytime multiple sleep latency test (MSLT). HLA typing was performed for all subjects. One relative (2.9%) was diagnosed as suffering from narcolepsy with cataplexy. Nearly 30% of the relatives fulfilled the criteria of narcolepsy spectrum disorder (shortened mean sleep latency [MSL] and/or the presence of sleep onset REM periods [SOREMPs]). When using the population data for comparison, the relative risk of narcolepsy in first-degree relatives was 85.3. The odds ratio of narcolepsy spectrum disorder in first-degree relatives was 5.8 (95% CI: 1.2 – 29.3) when compared to healthy controls. There existed 6 multiplex families, in which all 10 relatives with narcolepsy spectrum disorders, including all 3 relatives with multiple SOREMPs, were positive for HLA DQB1*0602. Conclusions: Our study demonstrated a definitive familial aggregation of narcolepsy, narcolepsy spectrum disorders, and possibly cataplexy in Hong Kong Chinese. This familial aggregation supported an inherited basis for narcolepsy spectrum. The tight co-segregation of HLA DQB1*0602 and narcolepsy spectrum disorders might suggest that HLA typing, especially DQB1*0602, at least partly confer the familial risk of narcolepsy. In addition, our study suggested that the subjective questionnaire measurements including Ullanlinna Narcolepsy Scale and Epworth Sleepiness Scale were unable to detect the presence of narcolepsy spectrum disorders among the relatives. A stringent objective measurement-based design for family studies is suggested for future study. Further studies are indicated for the determination

Comparing HLA shared epitopes in French Caucasian patients with scleroderma.

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Doua F Azzouz

Full Text Available Although many studies have analyzed HLA allele frequencies in several ethnic groups in patients with scleroderma (SSc, none has been done in French Caucasian patients and none has evaluated which one of the common amino acid sequences, (67FLEDR(71, shared by HLA-DRB susceptibility alleles, or (71TRAELDT(77, shared by HLA-DQB1 susceptibility alleles in SSc, was the most important to develop the disease. HLA-DRB and DQB typing was performed for a total of 468 healthy controls and 282 patients with SSc allowing FLEDR and TRAELDT analyses. Results were stratified according to patient's clinical subtypes and autoantibody status. Moreover, standardized HLA-DRß1 and DRß5 reverse transcriptase Taqman PCR assays were developed to quantify ß1 and ß5 mRNA in 20 subjects with HLA-DRB1*15 and/or DRB1*11 haplotypes. FLEDR motif is highly associated with diffuse SSc (χ(2 = 28.4, p<10-6 and with anti-topoisomerase antibody (ATA production (χ(2 = 43.9, p<10-9 whereas TRAELDT association is weaker in both subgroups (χ(2 = 7.2, p = 0.027 and χ(2 = 14.6, p = 0.0007 respectively. Moreover, FLEDR motif- association among patients with diffuse SSc remains significant only in ATA subgroup. The risk to develop ATA positive SSc is higher with double dose FLEDR than single dose with respectively, adjusted standardised residuals of 5.1 and 2.6. The increase in FLEDR motif is mostly due to the higher frequency of HLA-DRB1*11 and DRB1*15 haplotypes. Furthermore, FLEDR is always carried by the most abundantly expressed ß chain: ß1 in HLA DRB1*11 haplotypes and ß5 in HLA-DRB1*15 haplotypes.In French Caucasian patients with SSc, FLEDR is the main presenting motif influencing ATA production in dcSSc. These results open a new field of potential therapeutic applications to interact with the FLEDR peptide binding groove and prevent ATA production, a hallmark of severity in SSc.

PREVALENCE OF CELIAC DISEASE PREDISPOSING GENOTYPES, INCLUDING HLA-DQ2.2 VARIANT, IN BRAZILIAN CHILDREN.

Science.gov (United States)

Selleski, Nicole; Almeida, Lucas Malta; Almeida, Fernanda Coutinho de; Pratesi, Claudia Beatriz; Nóbrega, Yanna Karla de Medeiros; Gandolfi, Lenora

2018-01-01

Celiac disease is an autoimmune enteropathy triggered by the ingestion of gluten in genetically susceptible individuals. Almost all celiac patients carry immune recognition genes coding for HLA-DQ2.5 and DQ8 heterodimers. Over the last few years, great importance has been given to HLA-DQ2.2 as probable predisposing variant, although controversies still exist regarding its relevance. The aim of our study was to determine the possible existence of an association between HLA-DQ2.2 and celiac disease in Brazilian children by analyzing the prevalence of the predisposing variants for celiac disease in a representative group of children of a population in which this determination is still missing. HLA-DQ typing was performed in samples from a group of celiac (n=100) and non-celiac children (n=110). All samples were tested for the presence of the following variants: DQA1*05-DQB1*02 (DQ2.5), DQA1*03-DQB1*03:02 (DQ8) and DQA1*02:01-DQB1*02:02 (DQ2.2). Fisher`s exact test was used for statistical analysis. In the group of 100 celiac children, 78 (78%) were positive for DQ2, 13 (13 %) were DQ2/DQ8 and 6 (6%) were DQ8 positives. The HLA-DQ pattern in the 110 non-celiac children was as follows: positive for DQ2 in 33 (29.9%) samples, in 2 (1.8 %) was positive for DQ2/DQ8 and in 15 (13.6%) was positive for DQ8. We found significant differences between the distribution of some but not all of the analyzed alleles when comparing celiac and non-celiac children. The genotyping of celiac disease HLA-DQ predisposing alleles showed similarities with HLA-DQ patterns found in both European and non-European populations, which may be a reflection of the miscegenation, which gave origin to the current Brazilian population. No significant association was found between DQ2.2 variant and celiac disease in the studied population.

PREVALENCE OF CELIAC DISEASE PREDISPOSING GENOTYPES, INCLUDING HLA-DQ2.2 VARIANT, IN BRAZILIAN CHILDREN

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Nicole SELLESKI

Full Text Available ABSTRACT BACKGROUND: Celiac disease is an autoimmune enteropathy triggered by the ingestion of gluten in genetically susceptible individuals. Almost all celiac patients carry immune recognition genes coding for HLA-DQ2.5 and DQ8 heterodimers. Over the last few years, great importance has been given to HLA-DQ2.2 as probable predisposing variant, although controversies still exist regarding its relevance. OBJECTIVE: The aim of our study was to determine the possible existence of an association between HLA-DQ2.2 and celiac disease in Brazilian children by analyzing the prevalence of the predisposing variants for celiac disease in a representative group of children of a population in which this determination is still missing. METHODS: HLA-DQ typing was performed in samples from a group of celiac (n=100 and non-celiac children (n=110. All samples were tested for the presence of the following variants: DQA1*05-DQB1*02 (DQ2.5, DQA1*03-DQB1*03:02 (DQ8 and DQA1*02:01-DQB1*02:02 (DQ2.2. Fisher`s exact test was used for statistical analysis. RESULTS: In the group of 100 celiac children, 78 (78% were positive for DQ2, 13 (13 % were DQ2/DQ8 and 6 (6% were DQ8 positives. The HLA-DQ pattern in the 110 non-celiac children was as follows: positive for DQ2 in 33 (29.9% samples, in 2 (1.8 % was positive for DQ2/DQ8 and in 15 (13.6% was positive for DQ8. We found significant differences between the distribution of some but not all of the analyzed alleles when comparing celiac and non-celiac children. CONCLUSION: The genotyping of celiac disease HLA-DQ predisposing alleles showed similarities with HLA-DQ patterns found in both European and non-European populations, which may be a reflection of the miscegenation, which gave origin to the current Brazilian population. No significant association was found between DQ2.2 variant and celiac disease in the studied population.

HLA genes in Chimila Amerindians (Colombia), the Peopling of ...

African Journals Online (AJOL)

Our aim is to study the HLA-A, -B, -C, -DRB1 and -DQB1 gene frequencies in the Chimila Amerindian (Colombia) ethnic group. Results are compared with other World populations in order to obtain information about Chimila and Amerindian Health promotion, Amerindian origins and America peopling. Written consent was ...

DNA typing of HLA class II genes in native inhabitants of Chukotka

Energy Technology Data Exchange (ETDEWEB)

Krylov, M.Yu.; Erdesz, S.; Alexeeva, L.I. [Institute of Rheumatology, Moscow (Russian Federation)

1995-06-01

Polymorphism of HLA class II genes was studied in native Chukotka inhabitants with the use of DNA oligotyping. The characteristics of the distribution of allelic variants of the loci HLA-DRB1, -DQA1, -DQB1, and -DPB1 were revealed; they were similar to those of other Subarctic Mongoloid populations and different from those for comparable populations of other climatic and geographic zones. Our data suggest that the specific features found for the distributions of some alleles of the loci examined are related to the geographic variation in the HLA gene system studied. 20 refs., 4 tabs.

1 RESEARCH ARTICLE Genetic diversity of Cahi DRB and DQB ...

Indian Academy of Sciences (India)

DADA

is a scarcity of research database for allelic association of DRB and DQB alleles .... typed for genotype of DRB or DQB1. μ = the intercept; Cj = cohort effect; ... amino acid occurs divided by the total number of protein examined. .... Alleles in low ranking genotypes and high ranking genotypes were exclusive to .... Health Prod.

Origin of Aymaras from Bolivia and their relationship with other Amerindians according to HLA genes.

Science.gov (United States)

Arnaiz-Villena, A; Siles, N; Moscoso, J; Zamora, J; Serrano-Vela, J I; Gomez-Casado, E; Castro, M J; Martinez-Laso, J

2005-04-01

Aymara Amerindians from the Titicaca Lake Andean highlands are studied for HLA-A, HLA-B, HLA-DRB1 and HLA-DQB1 gene frequencies. Genetic distances, neighbour-joining and correspondence analyses are performed by using other Amerindian and worldwide populations (15384 chromosomes are studied). The HLA genetic profile of Aymaras is different from neighbouring and language-related Quechuas (Incas). Both Quechuas and Aymaras seem to present an HLA-DRB1*0901 high frequency, which is present in a very low frequency or absent in Mesoamericans (Mazatecans, Mayans) and most studied Amerindians. Moreover, it is observed a closer relatedness of Aymaras with Amerindians from the Amazon Basin and Chaco lowlands, compared to Quechuans.

Una aproximación al significado biológico del polimorfismo del Complejo Mayor de Histocompatibilidad. El modelo de la asociación HLA y ARJ

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Gloria Garavito

2002-01-01

Full Text Available Objetivos. Llevar a cabo una actualización del estado del arte acerca del significado biológico del polimorfismo del sistema genético Complejo Mayor de Histocompatibilidad (CMH. Revisar la literatura relacionada con la asociación de los antígenos de histocompatibilidad en el humano (HLA y la susceptibilidad o resistencia al desarrollo de la artritis reumatoidea juvenil (ARJ. Presentar un modelo hipotético para la comprensión de la susceptibilidad genética a desarrollar ARJ. Fuente de datos. Las referencia bibliográficas que soportan este artículo se obtuvieron a través de búsquedas en las siguientes bases de datos: Pubmed, Ovid, Ebsco. Inicialmente se encontraron 139 artículos, de los cuales se seleccionaron 75. Se incluyó también información del desarrollo de un proyecto de investigación de nuestro grupo, «Polimorfismo molecular de los antígenos HLA en ARJ» (cod. Colciencias 1215-04-280-96. Resultados. L artritis reumatoidea juvenil (ARJ es la enfermedad más común en la práctica reumatológica pediátrica y la menos estudiada inmunogenéticamente. A diferencia de la artritis reumatoide (AR del adulto, la ARJ tiene ciertas variantes clínicas, lo que la hace más interesante desde el punto de vista genético (fenotipos. En su etiopatogenia se han identificado varios factores que en su conjunto explicarían el inicio y la perpetuación de la respuesta inflamatoria que afecta las articulaciones y tejidos vecinos, y que de no ser controlados llegan a destruirlos, tal como sucede en otras enfermedades autoinmunes. La patogénesis de la enfermedad puede determinarse por alteraciones a nivel de complejo trimolecular, constituido por un antígeno putativo, el receptor de linfocitos T y el Complejo Mayor de Histocompatibilidad (CMH. Nuestro grupo durante los últimos 4 años ha estado estudiando la asociación entre ARJ y el polimorfismo de los alelos HLA DRB1* y DQB1* en niños mestizos de nuestro país. Los resultados son

HLA-DQ genetic risk gradient for type 1 diabetes and celiac disease in northwestern Mexico.

Science.gov (United States)

Mejía-León, M E; Ruiz-Dyck, K M; Calderón de la Barca, A M

2015-01-01

Type 1 diabetes (T1D) and celiac disease (CD) are the 2 most common autoimmune childhood diseases that share their HLA-DQ2 and DQ8 genetic origin. There has currently been an increase in both diseases worldwide. In children from the low-population State of Sonora (15 inhabitants/km(2)) in north-western Mexico, there is no information on their genetic risk or the distribution of the related alleles in the general population. To compare the HLA-DQ allele frequency in a representative sample of newborns from Sonora with that of T1D and CD patients to determine the risk gradient, and to identify the presence of celiac autoimmunity in the T1D group. The study included 397 Sonoran newborns, with 44 cases of T1D, and 25 CD cases. The CD and T1D cases were clinically diagnosed by specialists at the Hospital Infantil del Estado de Sonora, and the autoantibodies were determined by ELISA. Whole blood was collected, gDNA was extracted, and HLA-DQ2 and DQ8 were typed by PCR-SSP. The risk gradient was calculated by comparing the allele frequencies of the cases with those of the newborns. The Sonoran HLA-DQ risk heterodimer proportion was 16.1% for HLA-DQ2 and 13.6% for HLA-DQ8, with an HLA-DQ2:HLA-DQ8 ratio of 1.2:1. The DQ8/DQ2 genotype represented a 1:14 risk for T1D, whereas the DQ8/DQB1*0201 combination showed a 1:6 risk for CD. The prevalence of CD autoimmunity in T1D children was 7%. The Sonoran population has a distinctive HLA-DQ allele distribution due to its ancestry. The HLA-DQ8 combinations with DQ2 or one of its alleles conferred the highest risk for both diseases, and T1D and CD frequently appear together. Copyright © 2015 Asociación Mexicana de Gastroenterología. Published by Masson Doyma México S.A. All rights reserved.

DNA polymorphism of HLA class II genes in alopecia areata

DEFF Research Database (Denmark)

Morling, N; Frentz, G; Fugger, L

1992-01-01

fragment was increased to 65.0 per cent compared to 23.2 per cent in controls (RR = 6.1; p less than 10(-3)) suggesting that the previously reported associations between AA and both DR4 and DR5 is secondary to an association between AA and DQB1*0301, which codes for the beta-chain of the HLA-DQ molecule...

Frecuencias alélicas, genotípicas y haplotípicas HLA-A, HLA-B, HLA-DRB1 en donantes fallecidos, Medellín, Colombia

OpenAIRE

Libia M. Rodríguez; Mabel C. Giraldo; Natalia García; Laura Velásquez; Sara C. París; Cristiam M. Álvarez; Luis F. García

2007-01-01

Introducción. La caracterización genética del sistema HLA es de gran utilidad en estudios antropogenéticos, en la comprensión de mecanismos asociados a susceptibilidad o resistencia a diversas enfermedades, en los fenómenos inmunológicos durante el embarazo y en la selección de donantes/receptores en trasplantes de órganos. Objetivo. Determinar las frecuencias alélicas, genotípicas y haplotípicas HLA-A, -B, -DRB1 en donantes fallecidos en Medellín. Materiales y métodos. Se incluyeron 92...

Frecuencias alélicas, genotípicas y haplotípicas HLA-A, HLA-B, HLA-DRB1 en donantes fallecidos, Medellín, Colombia

OpenAIRE

Rodríguez, Libia M; Giraldo, Mabel C; García, Natalia; Velásquez, Laura; París, Sara C; Álvarez, Cristiam M; García, Luis F

2007-01-01

Introducción. La caracterización genética del sistema HLA es de gran utilidad en estudios antropogenéticos, en la comprensión de mecanismos asociados a susceptibilidad o resistencia a diversas enfermedades, en los fenómenos inmunológicos durante el embarazo y en la selección de donantes/receptores en trasplantes de órganos. Objetivo. Determinar las frecuencias alélicas, genotípicas y haplotípicas HLA-A, -B, -DRB1 en donantes fallecidos en Medellín. Materiales y métodos. Se incluyeron 926 dona...

Effect of T-cell-epitope matching at HLA-DPB1 in recipients of unrelated-donor haemopoietic-cell transplantation: a retrospective study

Science.gov (United States)

Fleischhauer, Katharina; Gooley, Theodore; Malkki, Mari; Bardy, Peter; Bignon, Jean-Denis; Dubois, Valérie; Horowitz, Mary M; Madrigal, J Alejandro; Morishima, Yasuo; Oudshoorn, Machteld; Ringden, Olle; Spellman, Stephen; Velardi, Andrea; Zino, Elisabetta; Petersdorf, Effie W

2013-01-01

Summary Background The risks after unrelated-donor haemopoietic-cell transplantation with matched HLA-A, HLA-B, HLA-C, HLA-DRB1, HLA-DQB1 alleles between donor and recipient (10/10 matched) can be decreased by selection of unrelated donors who also match for HLA-DPB1; however, such donors are difficult to find. Classification of HLA-DPB1 mismatches based on T-cell-epitope groups could identify mismatches that might be tolerated (permissive) and those that would increase risks (non-permissive) after transplantation. We did a retrospective study to compare outcomes between permissive and non-permissive HLA-DPB1 mismatches in unrelated-donor haemopoietic-cell transplantation. Methods HLA and clinical data for unrelated-donor transplantations submitted to the International Histocompatibility Working Group in haemopoietic-cell transplantation were analysed retrospectively. HLA-DPB1 T-cell-epitope groups were assigned according to a functional algorithm based on alloreactive T-cell crossreactivity patterns. Recipients and unrelated donors matching status were classified as HLA-DPB1 match, non-permissive HLA-DPB1 mismatch (those with mismatched T-cell-epitope groups), or permissive HLA-DPB1 mismatch (those with matched T-cell-epitope groups). The clinical outcomes assessed were overall mortality, non-relapse mortality, relapse, and severe (grade 3–4) acute graft-versus-host disease (aGvHD). Findings Of 8539 transplantations, 5428 (64%) were matched for ten of ten HLA alleles (HLA 10/10 matched) and 3111 (36%) for nine of ten alleles (HLA 9/10 matched). Of the group overall, 1719 (20%) were HLA-DPB1 matches, 2670 (31%) non-permissive HLA-DPB1 mismatches, and 4150 (49%) permissive HLA-DPB1 mismatches. In HLA 10/10-matched transplantations, non-permissive mismatches were associated with a significantly increased risk of overall mortality (hazard ratio [HR] 1·15, 95% CI 1·05–1·25; p=0·002), non-relapse mortality (1·28, 1·14–1·42; pKarolinska Institutet; and

Discovery of the rare HLA-B*39:77 allele in an unrelated Taiwanese bone marrow stem cell donor using the sequence-based typing method.

Science.gov (United States)

Yang, K L; Lee, S K; Lin, P Y

2013-08-01

We detected a rare HLA-B locus allele, B*39:77, in a Taiwanese unrelated marrow stem cell donor in our routine HLA sequence-based typing (SBT) exercise for a possible haematopoietic stem cell donation. In exons 2, 3 and 4, the DNA sequence of B*39:77 is identical to the sequence of B*39:01:01:01 except one nucleotide at nucleotide position 733 (G->A) in exon 4. The nucleotide variation caused one amino acid alteration at residue 221 (Gly->Ser). B*39:77 was probably derived from a nucleotide substitution event involving B*39:01:01:01. The probable HLA-A, -B, -C, -DRB1 and -DQB1 haplotype in association with B*39:77 may be deduced as A*02:01-B*39:77-C*07:02-DRB1*08:03-DQB1*06:01. Our discovery of B*39:77 in Taiwanese adds further polymorphism of B*39 variants in Taiwanese population. © 2013 John Wiley & Sons Ltd.

Epitopes recognized by CBV4 responding T cells: effect of type 1 diabetes and associated HLA-DR-DQ haplotypes

International Nuclear Information System (INIS)

Marttila, Jane; Hyoety, Heikki; Naentoe-Salonen, Kirsti; Simell, Olli; Ilonen, Jorma

2004-01-01

The present study aimed at characterizing the epitopes recognized by coxsackievirus B4 (CBV4)-specific T-cell lines established from 23 children with type 1 diabetes (T1D) and 29 healthy children with T1D risk-associated HLA genotypes. Responsiveness to VP1 region was dependent on the specific infection history as 55% of the T-cell lines from donors with neutralizing antibodies to CBV serotypes responded to VP1 peptides compared to none of the T-cell lines from other donors (P = 0.01). The pattern of recognized peptides was dependent of the HLA genotype. Forty-two percent of the T-cell lines from donors carrying the HLA-(DR4)-DQB1*0302 haplotype responded to VP1 peptides 71-80 compared to none of the T-cell lines from donors without this haplotype (P = 0.02). No evidence for the existence of diabetes-specific epitopes was found. Only few epitopes were exclusive recognized by T cells from diabetic children, and in each case only one or two T-cell lines were responding

HLA Typing and Celiac Disease in Moroccans

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Daniela Piancatelli

2017-01-01

Full Text Available Genetic and environmental factors are responsible for differences in the prevalence of some diseases across countries. Human leukocyte antigen (HLA allele frequencies in North African populations show some differences in their distribution compared to Europeans, Mediterraneans, and sub-Saharans, and some specific alleles and haplotypes could be clinically relevant. Celiac disease (CD has been fast increasing in prevalence in North Africa; but few immunogenetic data are available for this area, in which a high prevalence of the disease has been described. In this report, we assess and discuss results of HLA class II (HLA-DQA1/DQB1/DRB1 typing in Moroccan patients with CD and compare them with a control population from Morocco—genetically well characterized—and with other North African, Mediterranean, and European populations. The classical HLA-DQ associations were confirmed in Moroccans with CD. The high frequency of DQ2.5 homozygosity (45.2% found in Moroccans with CD was noteworthy as compared with other populations (23%–32%. The genetic risk gradient for CD, identified by previous studies, has been confirmed in Moroccans with some differences, mainly concerning DQ8 genotypes. This study provides the immunogenetic framework of CD in Moroccans and confirms the need to learn more about associations with additional HLA and non-HLA genetic factors.

Determinación de HLA en pacientes con Síndrome de Parry Romberg atendidos en el Servicio de Cirugía Plástica y Reconstructiva del Hospital General "Dr. Manuel Gea González"

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Damián Palafox

disminución del HLA DR7 (2% en SPR vs 11% en sujetos sanos. p=0.03, OR: 0.17, IC 95% 0.02-1.2 Además, que el HLA DR16 es parte de los haplotipos HLA- DRB1*16, DQB1*0301, en combinación con los alelos HLA-B*39, B*15, y B*35. En población sana el alelo de DQ es DQB0502. Conclusiones. A nuestro conocimiento, nunca antes se había realizado un estudio a esta escala y de ésta naturaleza en Parry Romberg a nivel mundial. Los datos sugieren que el haplotipo de riesgo para Parry Romberg es HLA-DRB1*16- DQB1*0301. Dado que este haplotipo es de origen indígena, sugiere que el mestizo mexicano que padece el síndrome está influido por el fondo genético amerindio, y puesto que los alelos de riesgo (DR11, DR1 y DR3 para las enfermedades típicamente relacionadas al síndrome estuvieron disminuidos, sugiere que el Síndrome de Parry Romberg es una entidad clínica independiente, única y extraordinaria.

HLA allele associations in idiopathic recurrent spontaneous abortion patients from India

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U Shankarkumar

2008-01-01

Full Text Available Background : Rejection of semiallogenic foetus in recurrent spontaneous abortion (RSA has been postulated to be a consequence of genetic and immunological phenomena. Aim: To evaluate the role of human leukocyte antigen (HLA alleles in RSA in Indian couples. Settings and Design : A case-control study. Materials and Methods : Eighty-one randomly selected couples with unexplained three or more RSAs and a control group of 97 couples with live birth belonging to the same ethnic background, referred to the Gynaecology Department, KEM Hospital were included in the case-control study. Serological HLA A and B typing was done followed by molecular subtypes, defined using PCR-SSOP technique for HLA A, B, and C in 40 couples and DRB1FNx01 and DQB1FNx01 in 28 couples which were then compared with appropriate case 46 and 88 controls. Results : Serologically A3 (15.43% vs . 4.43%; odds ratio (OR = 4.34; P = 0.0002 and B17 (25.3% vs . 11.34%; OR = 3.49; P = 0.0001 were increased. Haplotype A1-B17 was significantly increased. Molecular subtyping revealed that AFNx01030102 (11.25% vs . 4.34%; OR = 3.00; P = 0.07, BFNx015701 (11.25% vs . 1.08%; OR = 13.10; P = 0.003, CwFNx01120201 (25% vs . 4.34%; OR = 10.50; P = 2.05E-05, HLA DRB1FNx01030101 (17.85% vs . 3.40%; OR = 7.6; P = 0.0001, DRB1FNx01150101 (32.14% vs . 13.63%; OR = 4.8; P = 0.0003, and DQB1FNx01060101 (35.71% vs . 29.34%; OR = 2.3; P = 0.004 were significantly increased in patients. A differential association was noticed when compared with reported world RSA patients. Conclusion: The HLA alleles AFNx01030101, BFNx015701, CwFNx01120201, DRB1FNx01030101, and DRB1FNx01150101 as well as their associated ancestral haplotype may play a significant role in development of RSA in India.

Human leucocyte antigens class II allele and haplotype association with Type 1 Diabetes in Madeira Island (Portugal).

Science.gov (United States)

Spínola, H; Lemos, A; Couto, A R; Parreira, B; Soares, M; Dutra, I; Bruges-Armas, J; Brehm, A; Abreu, S

2017-12-01

This study confirms for Madeira Island (Portugal) population the Type 1 Diabetes (T1D) susceptible and protective Human leucocyte antigens (HLA) markers previously reported in other populations and adds some local specificities. Among the strongest T1D HLA associations, stands out, as susceptible, the alleles DRB1*04:05 (OR = 7.3), DQB1*03:02 (OR = 6.1) and DQA1*03:03 (OR = 4.5), as well as the haplotypes DRB1*04:05-DQA1*03:03-DQB1*03:02 (OR = 100.9) and DRB1*04:04-DQA1*03:01-DQB1*03:02 (OR = 22.1), and DQB1*06:02 (OR = 0.07) and DRB1*15:01-DQA1*01:02-DQB1*06:02 (OR = 0.04) as protective. HLA-DQA1 positive for Arginine at position 52 (Arg52) (OR = 15.2) and HLA-DQB1 negative for Aspartic acid at the position 57 (Asp57) (OR = 9.0) alleles appear to be important genetic markers for T1D susceptibility, with higher odds ratio values than any single allele and than most of the haplotypes. Genotypes generated by the association of markers Arg52 DQA1 positive and Asp57 DQB1 negative increase T1D susceptibility much more than one would expected by a simple additive effect of those markers separately (OR = 26.9). This study also confirms an increased risk for DRB1*04/DRB1*03 heterozygote genotypes (OR = 16.8) and also a DRB1*04-DQA1*03:01-DQB1*03:02 haplotype susceptibility dependent on the DRB1*04 allele (DRB1*04:01, OR = 7.9; DRB1*04:02, OR = 3.2; DRB1*04:04, OR = 22.1). © 2017 John Wiley & Sons Ltd.

Maternal HY-restricting HLA class II alleles are associated with poor long-term outcome in recurrent pregnancy loss after a boy

DEFF Research Database (Denmark)

Kolte, Astrid Marie; Steffensen, Rudi; Christiansen, Ole Bjarne

2016-01-01

PROBLEM: Women with secondary recurrent pregnancy loss (RPL) after a boy have a reduced chance of live birth in the first pregnancy after referral if they carry HY-restricting HLA class II alleles, but long-term chance of live birth is unknown. METHODS OF STUDY: Live birth was compared for 540...... women with unexplained secondary RPL according to firstborn's sex and maternal carriage of HLA-DRB3*03:01, HLA-DQB1*05:01/02, HLA-DRB1*15, and HLA-DRB1*07. The groups were compared by Cox proportional hazard ratios. RESULTS: For women with at firstborn boy, maternal carriage of HY-restricting HLA class...... of HY-restricting HLA class II alleles decreases long-term chance of live birth in women with RPL after a boy....

High-sensitivity HLA typing by Saturated Tiling Capture Sequencing (STC-Seq).

Science.gov (United States)

Jiao, Yang; Li, Ran; Wu, Chao; Ding, Yibin; Liu, Yanning; Jia, Danmei; Wang, Lifeng; Xu, Xiang; Zhu, Jing; Zheng, Min; Jia, Junling

2018-01-15

Highly polymorphic human leukocyte antigen (HLA) genes are responsible for fine-tuning the adaptive immune system. High-resolution HLA typing is important for the treatment of autoimmune and infectious diseases. Additionally, it is routinely performed for identifying matched donors in transplantation medicine. Although many HLA typing approaches have been developed, the complexity, low-efficiency and high-cost of current HLA-typing assays limit their application in population-based high-throughput HLA typing for donors, which is required for creating large-scale databases for transplantation and precision medicine. Here, we present a cost-efficient Saturated Tiling Capture Sequencing (STC-Seq) approach to capturing 14 HLA class I and II genes. The highly efficient capture (an approximately 23,000-fold enrichment) of these genes allows for simplified allele calling. Tests on five genes (HLA-A/B/C/DRB1/DQB1) from 31 human samples and 351 datasets using STC-Seq showed results that were 98% consistent with the known two sets of digitals (field1 and field2) genotypes. Additionally, STC can capture genomic DNA fragments longer than 3 kb from HLA loci, making the library compatible with the third-generation sequencing. STC-Seq is a highly accurate and cost-efficient method for HLA typing which can be used to facilitate the establishment of population-based HLA databases for the precision and transplantation medicine.

Replication of genome wide association studies on hepatocellular carcinoma susceptibility loci of STAT4 and HLA-DQ in a Korean population.

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Kim, Lyoung Hyo; Cheong, Hyun Sub; Namgoong, Suhg; Kim, Ji On; Kim, Jeong-Hyun; Park, Byung Lae; Cho, Sung Won; Park, Neung Hwa; Cheong, Jae Youn; Koh, InSong; Shin, Hyoung Doo; Kim, Yoon-Jun

2015-07-01

A recent genome-wide association study (GWAS) for hepatitis B virus (HBV)-related hepatocellular carcinoma (HCC) identified two loci (rs7574865 in STAT4 and rs9275319 in HLA-DQ) in a Chinese population. We attempted to replicate the associations between the two SNP loci and the risk of HCC in a Korean population. The rs7574865 in STAT4 and rs9275319 in HLA-DQ were genotyped in a total of 3838 Korean subjects composed of 287 HBV-related hepatocellular carcinoma patients, 671 chronic hepatitis B virus (CHB) patients, and 2880 population controls using TaqMan genotyping assay. Gene expression was measured by microarray. A logistic regression analysis revealed that rs7574865 in STAT4 and rs9275319 in HLA-DQ were associated with the risk of CHB (OR = 1.25, P = 0.0002 and OR = 1.57, P= 1.44 × 10(-10), respectively). However, these loci were no association with the risk of HBV-related HCC among CHB patients. In the gene expression analyses, although no significant differences in mRNA expression of nearby genes according to genotypes were detected, a significantly decreased mRNA expression in HCC subjects was observed in STAT4, HLA-DQA1, and HLA-DQB1. Although the genetic effects of two HCC susceptibility loci were not replicated, the two loci were found to exert susceptibility effects on the risk of CHB in a Korean population. In addition, the decreased mRNA expression of STAT4, HLA-DQA1, and HLA-DQB1 in HCC tissue might provide a clue to understanding their role in the progression to HCC. Copyright © 2015 Elsevier B.V. All rights reserved.

Genetic affinities of north and northeastern populations of India: inference from HLA-based study.

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Agrawal, S; Srivastava, S K; Borkar, M; Chaudhuri, T K

2008-08-01

India is like a microcosm of the world in terms of its diversity; religion, climate and ethnicity which leads to genetic variations in the populations. As a highly polymorphic marker, the human leukocyte antigen (HLA) system plays an important role in the genetic differentiation studies. To assess the genetic diversity of HLA class II loci, we studied a total of 1336 individuals from north India using DNA-based techniques. The study included four endogamous castes (Kayastha, Mathurs, Rastogies and Vaishyas), two inbreeding Muslim populations (Shias and Sunnis) from north India and three northeast Indian populations (Lachung, Mech and Rajbanshi). A total of 36 alleles were observed at DRB1 locus in both Hindu castes and Muslims from north, while 21 alleles were seen in northeast Indians. At the DQA1 locus, the number of alleles ranged from 11 to 17 in the studied populations. The total number of alleles at DQB1 was 19, 12 and 20 in the studied castes, Muslims and northeastern populations, respectively. The most frequent haplotypes observed in all the studied populations were DRB1*0701-DQA1*0201-DQB1*0201 and DRB1*1501-DQA1*0103-DQB1*0601. Upon comparing our results with other world populations, we observed the presence of Caucasoid element in north Indian population. However, differential admixturing among Sunnis and Shias with the other north Indians was evident. Northeastern populations showed genetic affinity with Mongoloids from southeast Asia. When genetic distances were calculated, we found the north Indians and northeastern populations to be markedly unrelated.

HLA diversity in the 1000 genomes dataset.

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Pierre-Antoine Gourraud

Full Text Available The 1000 Genomes Project aims to provide a deep characterization of human genome sequence variation by sequencing at a level that should allow the genome-wide detection of most variants with frequencies as low as 1%. However, in the major histocompatibility complex (MHC, only the top 10 most frequent haplotypes are in the 1% frequency range whereas thousands of haplotypes are present at lower frequencies. Given the limitation of both the coverage and the read length of the sequences generated by the 1000 Genomes Project, the highly variable positions that define HLA alleles may be difficult to identify. We used classical Sanger sequencing techniques to type the HLA-A, HLA-B, HLA-C, HLA-DRB1 and HLA-DQB1 genes in the available 1000 Genomes samples and combined the results with the 103,310 variants in the MHC region genotyped by the 1000 Genomes Project. Using pairwise identity-by-descent distances between individuals and principal component analysis, we established the relationship between ancestry and genetic diversity in the MHC region. As expected, both the MHC variants and the HLA phenotype can identify the major ancestry lineage, informed mainly by the most frequent HLA haplotypes. To some extent, regions of the genome with similar genetic or similar recombination rate have similar properties. An MHC-centric analysis underlines departures between the ancestral background of the MHC and the genome-wide picture. Our analysis of linkage disequilibrium (LD decay in these samples suggests that overestimation of pairwise LD occurs due to a limited sampling of the MHC diversity. This collection of HLA-specific MHC variants, available on the dbMHC portal, is a valuable resource for future analyses of the role of MHC in population and disease studies.

[The impact of HLA haplotype and alleles mismatches of donor-recipient pairs on outcome of haploidentical hematopoietic stem cell transplantation with a third part cord blood unit].

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Zhu, W J; He, J; Bao, X J; Yuan, X N; Li, Y; Xue, S L; Pan, Z J; Chen, J; Wu, D P

2016-07-01

To analyze allele mismatches of HLA- A, - B, - C, - DRB1, - DQB1 and haplotype mismatch of donor- recipient pairs on the outcome of haploidentical transplantation combined with a third part cord blood unit. 230 pairs of donor-recipient were performed HLA-A, B, C, DRB1, DQB1 typing using SBT and SSOP methods from January 2012 to December 2014. Pairs were divided into HLA- 5/10、6/10、7/10 and ≥8/10 groups according to HLA- A, B, C and DRB1 highresolution typing and matched degrees, the 3-year probability of overall survival (OS) for each group were 48.7%, 59.3%, 71.1%, 38.3% (P=0.068) respectively. HLA-6/10 matched group associated with significant favorable effect on OS compared with HLA- 5/10 matched one (P=0.041).When the HLA class I antigen matched on the recipient and donor, improved OS and event free survival (EFS) in HLA- 6/10 matched group than in HLA-5/10 matched one (P=0.017,P=0.088), especially in single HLA-A loci allele matched one (P=0.013,P=0.013), were observed. As to the third part cord blood unit, sharing the same haplotype with the recipient-donor pairs produced better platelet recovery than the misfit one (95.3%vs 86.2%,P= 0.007), similar result was found in terms of neutrophil recovery (98.8%vs 96.1% ,P=0.022). HLA locus mismatch and haplotype mismatch of the donor and recipient should be useful for selection of the most optimum donor. Co- infused of an unrelated cord blood unit sharing the same haplotype with the recipient-donor pairs could improve hematopoietic recovery.

HLA variants rs9271366 and rs9275328 are associated with systemic lupus erythematosus susceptibility in Malays and Chinese.

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Chai, H C; Phipps, M E; Othman, I; Tan, L P; Chua, K H

2013-02-01

Human leukocyte antigen (HLA) antigens and genes have long been reported associated with systemic lupus erythematosus (SLE) susceptibility in many populations. With the advance in technologies such as genome-wide association studies, many newly discovered SLE-associated single-nucleotide polymorphisms (SNPs) have been reported in recent years. These include HLA-DRB1/HLA-DQA1 rs9271366 and HLA-DQB1/HLA-DQA2 rs9275328. Our aim was to investigate these SNPs in a Malaysian SLE cohort. SNPs rs9271366 and rs9275328 were screened across 790 Malaysian citizens from three ethnic groups (360 patients and 430 healthy volunteers) by Taqman SNP genotyping assays. Allele and genotyping frequencies, Hardy-Weinberg equilibrium, Fisher's exact test and odds ratio were calculated for each SNP and ethnic group. Linkage disequilibrium and interaction between the two SNPs were also evaluated. The minor allele G and its homozygous genotype GG of HLA-DRB1/HLA-DQA1 rs9271366 significantly increased the SLE susceptibility in Malaysian patients, including those of Malay and Chinese ethnicity (odds ratio (OR) > 1, p < 0.05). As for HLA-DQB1/HLA-DQA2 rs9275328, the minor allele T and the heterozygous genotype CT conferred protective effect to SLE in Malaysians, as well as in Malays and Chinese, by having OR < 1 and p value <0.05. Both SNPs did not show associations to SLE in Indians. D' and r (2) values for the two SNPs in LD analysis were 0.941 and 0.065, respectively, with haplotype GC and AT being significantly associated with SLE (p < 5.0 × 10(-4)) after 10,000 permutations were performed. The MDR test clustered the genotype combinations of GG and CC, and AG and CC of rs9271366 and rs9275328, accordingly, as high-risk group, and the two SNPs interacted redundantly by removing 1.96% of the entropy. Our findings suggest that in addition to some classical HLA variants, rs9271366 and rs9275328 are additional polymorphisms worth considering in the Malaysian and possibly in

DNA polymorphism of HLA class II genes in systemic lupus erythematosus

DEFF Research Database (Denmark)

Cowland, J B; Andersen, V; Halberg, P

1994-01-01

We investigated the DNA restriction fragment length polymorphism (RFLP) of the major histocompatibility complex (MHC) genes: HLA-DRB, -DQA, -DQB, -DPB in 24 Danish patients with systemic lupus erythematosus (SLE) and in 102 healthy Danes. A highly significant increase of the frequency of the DR3...

HLA class II association with Type I allergy to house dust mite and Japanese cedar pollen in Japanese subjects

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Yasuaki Sadanaga

1998-01-01

Full Text Available We evaluated the incidence of the association of HLA class II phenotype and specific IgE responsiveness against house dust mite (HDM and/or Japanese cedar pollen (Jc in 176 patients with allergic rhinitis, with or without bronchial asthma, and 107 nonallergic subjects. Specific IgE antibody titration against the purified allergens Der f1 and Der f2 from HDM, and against Cry J1 and Cry J2 from Jc, was performed by using enzyme-linked immunosorbent assay (ELISA and radioimmunoassay (RIA in sera from all subjects. HLA class II oligotyping was performed by the polymerase chain reaction sequence specific oligonucleotide (PCR-SSO method on the DRB1*, DQA1*, DQB1* and DPB1* alleles using peripheral blood cells. The high IgE responders ≥ class 4 to the purified allergens were identified by using the IgE antibody reference concentration obtained by ELISA, RIA and routine IgE CAP RAST. Compared to the controls, the patients with both rhinitis and asthma showed significantly higher frequencies of DRB1* 0901, DQB1* 0303, and DPB1* 0401 alleles. High IgE responsiveness to HDM was associated with DRB1* 1101, 0901, DQB1* 0303, and DPB1*0401 alleles. The patients with anti-Der f1 IgE antibody concentration exceeding 72.2 ng/mL showed significantly elevated frequencies for DQB1*0401 and DPB1*0401 alleles, and those with anti Der f2 IgE antibody concentration exceeding 46.2 ng/mL showed significantly elevated frequencies for DPB1*0401 and 0901 alleles. High IgE responsiveness to Jc with Cry j1 and Cryj2was associated with the DRB1* 1201 alleles.

MHC-DQB1 Variation and Its Association with Resistance or Susceptibility to Cystic Echinococcosis in Chinese Merino Sheep

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Wenqiao Hui

2012-12-01

Full Text Available Cystic echinococcosis (CE, one of the world’s most geographically widespread diseases, still represents a considerable economic and public health significance, although a variety of methods has been used to control the disease. It has been demonstrated that genetic factors, especially variations in MHC loci, can influence the outcome of CE infection in the human population. The study described here was designed to determine whether variation in MHC-DQB1 was associated with susceptibility or resistance to CE in sheep. If so, it would lay a theoretical foundation for breeding disease resistance sheep in future. This study was carried out on 204 Chinese Merino sheep, including 101 CE sheep and 103 healthy controls. The polymorphism of MHC-DQB1 exon 2 was detected by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP method, and x2 test was used to compare genotype frequencies between CE sheep and healthy controls. A total of 22 alleles and 42 genotypes were identified in DQB1 exon 2 in Chinese Merino sheep. In addition, x2 test showed that frequencies of DQB1-TaqIaa and DQB1-HaeIIInn genotypes were significantly higher in the healthy group (82.5% and 57.3%, respectively than that in the CE group (57.4% and 28.9%, respectively (both p values = 0, OR = 0.286, 0.303, respectively, suggesting that these genotypes appeared to be associated with resistance to CE. Whereas, frequencies of DQB1-TaqIab and DQB1-HaeIIImn genotypes were significantly higher in the CE group (36.9% and 32.0%, respectively, as compared with the healthy group (16.5% and 11.15%, respectively (p = 0.001, 0.001 and OR = 2.963, 3.629, respectively, indicating that these genotypes might be associated with susceptibility to CE. It is concluded that the genetic polymorphism within MHC-DQB1 might influence immune responses to pathogens, thus leading to the development of CE or protection against CE in Chinese Merino sheep, which would pave the way for breeding

DNA polymorphism of HLA class II genes in pauciarticular juvenile rheumatoid arthritis

DEFF Research Database (Denmark)

Morling, N; Friis, J; Fugger, L

1991-01-01

We investigated the DNA restriction fragment length polymorphism (RFLP) of the major histocompatibility complex (MHC) class II genes: HLA-DRB, -DQA, -DQB, DPA, and -DPB in 54 patients with pauciarticular juvenile rheumatoid arthritis (PJRA) and in healthy Danes. The frequencies of DNA fragments a...

Association of HLA Class I and Class II genes with bcr-abl transcripts in leukemia patients with t(9;22) (q34;q11)

International Nuclear Information System (INIS)

Mundhada, Shailendra; Luthra, Rajyalakshmi; Cano, Pedro

2004-01-01

Based on the site of breakpoint in t(9;22) (q34;q11), bcr-abl fusion in leukemia patients is associated with different types of transcript proteins. In this study we have seen the association of HLA genes with different types of bcr-abl transcripts. The association could predict the bcr-abl peptide presentation by particular HLA molecules. The study included a total of 189 patients of mixed ethnicity with chronic myelogenous leukemia and acute lymphocytic leukemia who were being considered for bone marrow transplantation. Typing of bcr-abl transcripts was done by reverse transcriptase PCR method. HLA typing was performed by molecular methods. The bcr-abl and HLA association was studied by calculating the relative risks and chi-square test. Significant negative associations (p < 0.05) were observed with HLA-A*02 (b2a2, e1a2), -A*68 (b2a2, b3a2, e1a2), -B*14 (b2a2, b3a2, e1a2), -B*15 (b2a2, b3a2), -B*40 (b2a2), -DQB1*0303 (b2a2, b3a2), -DQB1*0603 (b2a2), -DRB1*0401 (e1a2), -DRB1*0701 (b3a2), and -DRB1*1101 (b2a2). The negative associations of a particular bcr-abl transcript with specific HLA alleles suggests that these alleles play a critical role in presenting peptides derived from the chimeric proteins and eliciting a successful T-cell cytotoxic response. Knowledge of differential associations between HLA phenotypes and bcr-abl fusion transcript types would help in developing better strategies for immunization with the bcr-abl peptides against t(9;22) (q34;q11)-positive leukemia

HLA class II influences humoral autoimmunity in patients with type 2 autoimmune hepatitis.

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Djilali-Saiah, Idriss; Fakhfakh, Amin; Louafi, Hamida; Caillat-Zucman, Sophie; Debray, Dominique; Alvarez, Fernando

2006-12-01

Type 2 autoimmune hepatitis (AIH) is characterized by the presence of anti-liver kidney microsome (anti-LKM-1) and/or anti-liver cytosol type 1 (anti-LC1) autoantibodies. However, the correlation between these autoantibodies and the genetic background has not been studied. Frequencies of HLA class II alleles were compared between the 60 Caucasian children with type 2 AIH and 313 control subjects. The anti-LKM1 antibody reactivity directed against antigenic sites of CYP2D6 was analysed by ELISA. HLA-DQB1 *0201 allele was found to be the primary genetic determinant of susceptibility to type 2 AIH by conferring the highest odd-ratio (OR = 6.4). HLA-DRB1 *03 allele was significantly increased (P LKM1 and anti-LC1 autoantibodies as well as in those with only anti-LC1(+) compared to those with anti-LKM1(+) alone. In contrast, HLA-DRB1 *07 allele was significantly associated (P LKM1(+) alone compared to groups with both anti-LKM and anti-LC1 or with LC1+ alone. Children with the DRB1 *07 allele develop anti-LKM1 autoantibodies having a more restricted specificity (2 epitopes) than to those having HLA-DRB1 *03 allele (5 epitopes). The HLA-DR locus is involved in autoantibody expression, while the DQ locus appears to be a critical determinant for the development of type 2 AIH.

Increased occurrence of anti-AQP4 seropositivity and unique HLA Class II associations with neuromyelitis optica (NMO), among Muslim Arabs in Israel.

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Brill, Livnat; Mandel, Micha; Karussis, Dimitrios; Petrou, Panayiota; Miller, Keren; Ben-Hur, Tamir; Karni, Arnon; Paltiel, Ora; Israel, Shoshana; Vaknin-Dembinsky, Adi

2016-04-15

Previous studies have revealed different human leukocyte antigen (HLA) associations in multiple sclerosis (MS) and neuromyelitis optica (NMO), further discriminating these two demyelinating pathological conditions. In worldwide analyses, NMO and opticospinal MS are represented at higher proportions among demyelinating conditions in African, East-Asian and Latin American populations. There are currently no data regarding the prevalence of NMO in Middle East Muslims. The population in Israel is diverse in many ways, and includes subpopulations, based on religion and ethnicity; some exhibit genetic homogeneity. In Israel, the incidence of MS is lower in the Muslim population than the Jewish population and Muslims carry different allele frequency distribution of HLA haplotypes. To evaluate the occurrence of anti-AQP4 seropositivity in the Israeli Muslim population among patients with central nervous system (CNS) demyelinating conditions; and to identify the HLA DR and DQ profiles of Muslim Arab Israeli patients with NMO spectrum of diseases (NMOSD). The prevalence of anti-AQP4 seropositivity was analyzed in 342 samples, obtained from patients with various CNS demyelinating conditions and in a validation set of 310 samples. HLA class II alleles (HLA-DRB1 and DQB1) were examined in DNA samples from 35 Israeli Muslim Arabs NMO patients and compared to available data from 74 Israeli Muslim controls. Our data reveal a significantly increased prevalence of anti-AQP4 seropositivity, indicative of NMOSD, in Muslim Arab Israeli patients with initial diagnosis of a CNS demyelinating syndrome. In this population, there was a positive association with the HLA-DRB1*04:04 and HLA-DRB1*10:01 alleles (p=0.03), and a strong negative association with the HLA-DRB1*07 and HLA-DQB1*02:02 alleles (p=0.003, p=0.002). Our findings indicate a possibly increased prevalence of NMOSD in Muslim Arabs in Israel with distinct (positive and negative) HLA associations. Further studies in patients with

Searching for Celiac Disease Screening-detected celiac disease in an HLA-genotyped birth cohort

OpenAIRE

Björck, Sara

2015-01-01

Objectives: Celiac disease is a common immune mediated enteropathy strongly associated with HLA-DQB1*02 (DQ2), *0302 (DQ8), or both and the presence of tissue transglutaminase autoantibodies (tTGA). Prevalence studies have revealed that most affected individuals go undetected because of subclinical signs or being asymptomatic rendering screening a method for identification. However, less is known about subclinical manifestations of screening-detected celiac disease during childhood and if the...

HLA in Brazilian Ashkenazic Jews with chronic dermatophytosis caused by Trichophyton rubrum Antígenos Leucocitários Humanos (HLA em Judeus Ashkenazitas Brasileiros portadores de dermatofitose crônica causada por Trichophyton rubrum

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Aya Sadahiro

2004-06-01

Full Text Available The frequency of HLA (Human Leucocyte Antigens was analyzed in 25 non-consanguineous Brazilian Ashkenazic Jews, resident in the city of São Paulo, Brazil, suffering from chronic dermatophytosis caused by T. rubrum, and in 25 non-infected individuals belonging to the same ethnic group. Statistically significant values (pA freqüência dos HLA foi analisada em 25 Judeus Ashkenazitas, não consangüíneos, residentes em São Paulo, Brasil, com dermatofitose crônica causada por T. rubrum e em 25 indivíduos sadios, pertencentes ao mesmo grupo étnico dos pacientes. Observou-se valor estatisticamente significante (p<0,05 para HLA-B14 associado a resistência à dermatofitose crônica enquanto HLA-DQB1*06 (p=0,05 possivelmente relacionado a susceptibilidade. Estes achados indicam que o desenvolvimento da dermatofitose crônica pode ser influenciado por genes localizados no cromossomo 6, na região do complexo principal de histocompatibilidade.

Association of HY-restricting HLA class II alleles with pregnancy outcome in patients with recurrent miscarriage subsequent to a firstborn boy

DEFF Research Database (Denmark)

Nielsen, Henriette Svarre; Steffensen, Rudi; Varming, Kim

2009-01-01

and in 203 of their children born prior to the miscarriages. The subsequent live birth in women with boys prior to the miscarriages compared with girls is lower in women with HY-restricting HLA class II alleles [odds ratio (OR): 0.17 (0.1-0.4), P = 0.0001]. One HY-restricting HLA class II allele in women...... with firstborn boys significantly reduces the chances of a live birth [OR: 0.46 (0.2-0.9), P = 0.02]. Two HY-restricting HLA class II alleles further reduced this chance [OR: 0.21 (0.1-0.7), P = 0.02]. HY-restricting HLA class II did not reduce the chances of a live birth in SRM women with firstborn girls. HY-restricting...... birth. This study explores the putative impact of known HY-presenting HLA alleles on future pregnancy outcome in women with at least three consecutive miscarriages following a birth [secondary recurrent miscarriage (SRM)]. HLA-A, -B, -DRB1, DRB3-5 and DQB1 genotyping was performed in 358 SRM patients...

HLA-DRB1*03:01 and HLA-DRB1*04:01 modify the presentation and outcome in autoimmune hepatitis type-1.

Science.gov (United States)

van Gerven, N M F; de Boer, Y S; Zwiers, A; Verwer, B J; Drenth, J P H; van Hoek, B; van Erpecum, K J; Beuers, U; van Buuren, H R; den Ouden, J W; Verdonk, R C; Koek, G H; Brouwer, J T; Guichelaar, M M J; Vrolijk, J M; Coenraad, M J; Kraal, G; Mulder, C J J; van Nieuwkerk, C M J; Bloemena, E; Verspaget, H W; Kumar, V; Zhernakova, A; Wijmenga, C; Franke, L; Bouma, G

2015-06-01

The classical human leukocyte antigen (HLA)-DRB1*03:01 and HLA-DRB1*04:01 alleles are established autoimmune hepatitis (AIH) risk alleles. To study the immune-modifying effect of these alleles, we imputed the genotypes from genome-wide association data in 649 Dutch AIH type-1 patients. We therefore compared the international AIH group (IAIHG) diagnostic scores as well as the underlying clinical characteristics between patients positive and negative for these HLA alleles. Seventy-five percent of the AIH patients were HLA-DRB1*03:01/HLA-DRB1*04:01 positive. HLA-DRB1*03:01/HLA-DRB1*04:01-positive patients had a higher median IAIHG score than HLA-DRB1*03:01/HLA-DRB1*04:01-negative patients (P<0.001). We did not observe associations between HLA alleles and alanine transaminase levels (HLA-DRB1*03:01: P=0.2; HLA-DRB1*04:01; P=0.5); however, HLA-DRB1*03:01 was independently associated with higher immunoglobulin G levels (P=0.04). The HLA-DRB1*04:01 allele was independently associated with presentation at older age (P=0.03) and a female predominance (P=0.04). HLA-DRB1*03:01-positive patients received immunosuppressive medication and liver transplantation. In conclusion, the HLA-DRB1*03:01 and HLA-DRB1*04:01 alleles are both independently associated with the aggregate diagnostic IAIHG score in type-1 AIH patients, but are not essential for AIH development. HLA-DRB1*03:01 is the strongest genetic modifier of disease severity in AIH.

Influence of HLA class I, HLA class II and KIRs on vertical transmission and chronicity of hepatitis C virus in children.

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A Ruiz-Extremera

Full Text Available There is evidence that maternal viral load of HCV during delivery influences the risk for Mother-to-child transmission (MTCT, but this does not explain all cases. We study the role of the immunogenetic profile (HLA, KIRs and KIR-ligand binding of mothers and children in HCV-MTCT and in chronicity in the children.79 HCV-RNA (+ mothers and their 98 children were included. 24 children were infected, becoming chronic in 8 cases and clearing in 16. HLA-class-I and II and KIRs were determined by Luminex.MTCT study: The presence of HLA-C1-ligand in mothers and/or their children reduces the risk of transmission (mothers: Pc = 0.011, children: P = 0.033, whereas the presence of HLA-C2C2-ligand in mothers increases it (Pc = 0.011. In children KIR2DL3-HLA-C1 is a protector factor (Pc = 0.011. Chronicity in children study: Maternal DQA1*01 allele (Pc = 0.027, KIR2DS1 (Pc = 0.011 or KIR3DS1 (Pc = 0.011 favours chronicity in the child. The presence of the DQB1*03 allele (Pc = 0.027 and KIR2DS3 (P = 0.056 in the child and homozygosity for KIR3DL1/3DL1 (Pc = 0.011 and for the HLA-Bw4/Bw4 ligand (P = 0.027 is associated with viral clearance, whereas the presence of HLA-Bw6 ligand (P = 0.027, the binding of KIR3DS1-HLA-Bw4 (P = 0.037 and heterozygosity for KIR3DL1/3DS1 (Pc = 0.011 favour viral chronicity. Mother/child allele matching: In the joint HLA analysis, matching was greater between mothers and children with chronic infection vs those who had cleared the virus (67%±4.1 vs 57%±1.2, P = 0.003.The HLA-C1 ligand in the mother is related to MTCT, while several genetic factors of the mother or child are involved in the chronification or clearance of infection in the child. Matching allelic data is considered to be an indicator of HCV chronicity in the child and can be used as a potential prognostic test. This implies that NK cells may play a previously undocumented role in protecting against MTCT and that both NK cell immunity and adaptive T-cell responses may

The HLA-net GENE[RATE] pipeline for effective HLA data analysis and its application to 145 population samples from Europe and neighbouring areas.

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Nunes, J M; Buhler, S; Roessli, D; Sanchez-Mazas, A

2014-05-01

In this review, we present for the first time an integrated version of the Gene[rate] computer tools which have been developed during the last 5 years to analyse human leukocyte antigen (HLA) data in human populations, as well as the results of their application to a large dataset of 145 HLA-typed population samples from Europe and its two neighbouring areas, North Africa and West Asia, now forming part of the Gene[va] database. All these computer tools and genetic data are, from now, publicly available through a newly designed bioinformatics platform, HLA-net, here presented as a main achievement of the HLA-NET scientific programme. The Gene[rate] pipeline offers user-friendly computer tools to estimate allele and haplotype frequencies, to test Hardy-Weinberg equilibrium (HWE), selective neutrality and linkage disequilibrium, to recode HLA data, to convert file formats, to display population frequencies of chosen alleles and haplotypes in selected geographic regions, and to perform genetic comparisons among chosen sets of population samples, including new data provided by the user. Both numerical and graphical outputs are generated, the latter being highly explicit and of publication quality. All these analyses can be performed on the pipeline after scrupulous validation of the population sample's characterisation and HLA typing reporting according to HLA-NET recommendations. The Gene[va] database offers direct access to the HLA-A, -B, -C, -DQA1, -DQB1, -DRB1 and -DPB1 frequencies and summary statistics of 145 population samples having successfully passed these HLA-NET 'filters', and representing three European subregions (South-East, North-East and Central-West Europe) and two neighbouring areas (North Africa, as far as Sudan, and West Asia, as far as South India). The analysis of these data, summarized in this review, shows a substantial genetic variation at the regional level in this continental area. These results have main implications for population genetics

Maternal HY-restricting HLA class II alleles are associated with poor long-term outcome in recurrent pregnancy loss after a boy.

Science.gov (United States)

Kolte, Astrid Marie; Steffensen, Rudi; Christiansen, Ole Bjarne; Nielsen, Henriette Svarre

2016-11-01

Women with secondary recurrent pregnancy loss (RPL) after a boy have a reduced chance of live birth in the first pregnancy after referral if they carry HY-restricting HLA class II alleles, but long-term chance of live birth is unknown. Live birth was compared for 540 women with unexplained secondary RPL according to firstborn's sex and maternal carriage of HLA-DRB3*03:01, HLA-DQB1*05:01/02, HLA-DRB1*15, and HLA-DRB1*07. The groups were compared by Cox proportional hazard ratios. For women with at firstborn boy, maternal carriage of HY-restricting HLA class II alleles decreased chance of live birth: 0 vs 1: hazard ratio 0.75 (95% CI 0.55-1.02); 0 vs 2: HR 0.62 (0.40-0.94). Carriage of HY-restricting HLA class II alleles decreased chance of live birth only if the firstborn was a boy: boy vs girl: HR 0.72 (95% CI 0.55-0.98). Maternal carriage of HY-restricting HLA class II alleles decreases long-term chance of live birth in women with RPL after a boy. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

The HLA Dictionary 2001: A Summary of HLA-A, -B, -C, -DRB1/3/4/5, -DQB1 Alleles and Their Association with Serologically Defined HLA-A, -B, -C, -DR and -DQ Antigens

National Research Council Canada - National Science Library

Schreuder, G

2001-01-01

...) the National Marrow Donor Program (NMDP) and individual laboratories. In addition a listing is provided of alleles which are expressed as antigens with serologic reaction patterns that differ from the well-established HLA specificities...

Shared HLA Class II in Six Autoimmune Diseases in Latin America: A Meta-Analysis

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Paola Cruz-Tapias

2012-01-01

Full Text Available The prevalence and genetic susceptibility of autoimmune diseases (ADs may vary depending on latitudinal gradient and ethnicity. The aims of this study were to identify common human leukocyte antigen (HLA class II alleles that contribute to susceptibility to six ADs in Latin Americans through a meta-analysis and to review additional clinical, immunological, and genetic characteristics of those ADs sharing HLA alleles. DRB1∗03:01 (OR: 4.04; 95%CI: 1.41–11.53 was found to be a risk factor for systemic lupus erythematosus (SLE, Sjögren's syndrome (SS, and type 1 diabetes mellitus (T1D. DRB1∗04:05 (OR: 4.64; 95%CI: 2.14–10.05 influences autoimmune hepatitis (AIH, rheumatoid arthritis (RA, and T1D; DRB1∗04:01 (OR: 3.86; 95%CI: 2.32–6.42 is a susceptibility factor for RA and T1D. Opposite associations were found between multiple sclerosis (MS and T1D. DQB1∗06:02 and DRB1∗15 alleles were risk factors for MS but protective factors for T1D. Likewise, DQB1∗06:03 allele was a risk factor for AIH but a protective one for T1D. Several common autoantibodies and clinical associations as well as additional shared genes have been reported in these ADs, which are reviewed herein. These results indicate that in Latin Americans ADs share major loci and immune characteristics.

HLA typing using genome wide data reveals susceptibility types for infections in a psychiatric disease enriched sample.

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Parks, Samuel; Avramopoulos, Dimitrios; Mulle, Jennifer; McGrath, John; Wang, Ruihua; Goes, Fernando S; Conneely, Karen; Ruczinski, Ingo; Yolken, Robert; Pulver, Ann E; Pearce, Brad D

2018-05-01

The infections Toxoplasma gondii (T. gondii), cytomegalovirus, and Herpes Simplex Virus Type 1 (HSV1) are common persistent infections that have been associated with schizophrenia and bipolar disorder. The major histocompatibility complex (MHC, termed HLA in humans) region has been implicated in these infections and these mental illnesses. The interplay of MHC genetics, mental illness, and infection has not been systematically examined in previous research. In a cohort of 1636 individuals, we used genome-wide association data to impute 7 HLA types (A, B, C, DRB1, DQA1, DQB1, DPB1), and combined this data with serology data for these infections. We used regression analysis to assess the association between HLA alleles, infections (individually and collectively), and mental disorder status (schizophrenia, bipolar disorder, controls). After Bonferroni correction for multiple comparisons, HLA C∗07:01 was associated with increased HSV1 infection among mentally healthy controls (OR 3.4, p = 0.0007) but not in the schizophrenia or bipolar groups (P > 0.05). For the multiple infection outcome, HLA B∗ 38:01 and HLA C∗12:03 were protective in the healthy controls (OR ≈ 0.4) but did not have a statistically-significant effect in the schizophrenia or bipolar groups. T. gondii had several nominally-significant positive associations, including the haplotypes HLA DRB∗03:01 ∼ HLA DQA∗05:01 ∼ HLA DQB∗02:01 and HLA B∗08:01 ∼ HLA C∗07:01. We identified HLA types that showed strong and significant associations with neurotropic infections. Since some of these associations depended on mental illness status, the engagement of HLA-related pathways may be altered in schizophrenia due to immunogenetic differences or exposure history. Copyright © 2018 Elsevier Inc. All rights reserved.

Seleção de doador de medula óssea ou sangue periférico Bone marrow or peripheral blood donor selection

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Noemi F. Pereira

2010-05-01

Full Text Available A compatibilidade HLA é o fator mais valorizado na escolha do doador de medula óssea voluntário, preconizando-se a realização de HLA de alta resolução nos locos HLA-A,B,C, DRB1 e DQB1. Tem sido dado preferência para o doador com consanguinidade alélica 8x8 (A,B,C, DRB1. Na presença de incompatibilidade na classe-I sugere-se a busca de doador com compatibilidade DQB1 (9x10. Já as incompatibilidades dos locos DPB1 não constituem critério de exclusão de doador, exceto quando existir presença de anticorpo contra o loco HLA-DP do doador.The HLA system is considered the most important factor in choosing a volunteer bone marrow donor with the recommendation of performing high resolution HLA tests for the HLA-A, B, C, DRB1 and DQB1 loci. A preference has been given for donor 8x8 (A, B, C, DRB1 allele matching. In the presence of class-I incompatibility a search for DQB1 (9x10 donor compatibility is suggested. The incompatibility of the DPB1 locus does not constitute exclusion of the donor, except when there is the presence of antibodies against the HLA-DP locus of the donor.

Association of HLA class II markers with autoantibody-negative ketosis-prone atypical diabetes compared to type 2 diabetes in a population of sub-Saharan African patients.

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Balti, Eric V; Ngo-Nemb, Marinette C; Lontchi-Yimagou, Eric; Atogho-Tiedeu, Barbara; Effoe, Valery S; Akwo, Elvis A; Dehayem, Mesmin Y; Mbanya, Jean-Claude; Gautier, Jean-François; Sobngwi, Eugene

2015-01-01

We investigated the association of HLA DRB1 and DQB1 alleles, haplotypes and genotypes with unprovoked antibody-negative ketosis-prone atypical diabetes (A(-) KPD) in comparison to type 2 diabetes (T2D). A(-) KPD and T2D sub-Saharan African patients aged 19-63 years were consecutively recruited. Patients positive for cytoplasmic islet cell, insulin, glutamic acid decarboxylase or islet antigen-2 autoantibodies were excluded. Odds ratios were obtained via logistic regression after considering alleles with a minimum frequency of 5% in the study population. Bonferroni correction was used in the case of multiple comparisons. Among the 130 participants, 35 (27%) were women and 57 (44%) were A(-) KPD. DRB1 and DQB1 allele frequencies were similar for both A(-) KPD and T2D patients; they did not confer any substantial risk even after considering type 1 diabetes susceptibility and resistance alleles. We found no association between A(-) KPD and the derived DRB1*07-DQB1*02:02 (OR: 0.55 [95%CI: 0.17-1.85], P=0.336); DRB1*11-DQB1*03:01 (OR: 2.42 [95%CI: 0.79-7.42], P=0.123); DRB1*15-DQB1*06:02 (OR: 0.87 [95%CI: 0.39-1.95], P=0.731) and DRB1*03:01-DQB1*02:01 (OR: 1.48 [95%CI: 0.55-3.96], P=0.437) haplotypes. Overall, we did not find any evidence of susceptibility to ketosis associated with DRB1 and DQB1 genotypes (all P>0.05) in A(-) KPD compared to T2D. Similar results were obtained after adjusting the analysis for age and sex. Factors other than DRB1 and DQB1 genotype could explain the propensity to ketosis in A(-) KPD. These results need to be confirmed in a larger population with the perspective of improving the classification and understanding of the pathophysiology of A(-) KPD. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

HLA-A, HLA-B, and HLA-DRB1 Allele and Haplotype Frequencies in Renal Transplant Candidates in a Population in Southern Brazil.

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Saito, Patrícia Keiko; Yamakawa, Roger Haruki; Noguti, Erika Noda; Bedendo, Gustavo Borelli; Júnior, Waldir Veríssimo da Silva; Yamada, Sérgio Seiji; Borelli, Sueli Donizete

2016-05-01

Very few studies have examined the diversity of human leukocyte antigens (HLA) in the Brazilian renal transplant candidates. The frequencies of the HLA-A, HLA-B, and HLA-DRB1 alleles, haplotypes and phenotypes were studied in 522 patients with chronic renal failure, renal transplant candidates, registered at the Transplant Centers in north/northwestern Paraná State, southern Brazil. Patients were classified according to the ethnic group (319 whites [Caucasians], 134 mestizos [mixed race descendants of Europeans, Africans, and Amerindians; browns or "pardos"] and 69 blacks). The HLA typing was performed by the polymerase chain reaction sequence-specific oligonucleotide method (PCR-SSO), combined with Luminex technology. In the analysis of the total samples, 20 HLA-A, 32 HLA-B, and 13 HLA-DRB1 allele groups were identified. The most frequent allele groups for each HLA locus were HLA-A*02 (25.4%), HLA-B*44 (10.9%), and HLA-DRB1*13 (13.9%). The most frequent haplotypes were HLA-A*01-B*08-DRB1*03 (2.3%), A*02-B*44-DRB1*07 (1.2%), and A*03-B*07-DRB1*11 (1.0%). Significant differences (P < 0.05) were observed in the HLA-A*68, B*08, and B*58 allele frequencies among ethnic groups. This study provides the first data on the HLA-A, HLA-B, and HLA-DRB1 allele, phenotype and haplotype frequencies of renal transplant candidates in a population in southern Brazil. © 2015 Wiley Periodicals, Inc.

HLA class II linkage disequilibrium and haplotype evolution in the Cayapa Indians of Ecuador

Energy Technology Data Exchange (ETDEWEB)

Trachtenberg, E.A.; Erlich, H.A. [Roche Molecular Systems, Alameda, CA (United States); Klitz, W. [Univ. of California, Berkeley, CA (United States)] [and others

1995-08-01

DNA-based typing of the HLA class II loci in a sample of the Cayapa Indians of Ecuador reveals several lines of evidence that selection has operated to maintain and to diversify the existing level of polymorphism in the class II region. As has been noticed for other Native American groups, the overall level of polymorphism at the DRB1, DQA1, DQB1, and DPB1 loci is reduced relative to that found in other human populations. Nonetheless, the relative eveness in the distribution of allele frequencies at each of the four loci points to the role of balancing selection in the maintenance of the polymorphism. The DQA1 and DQB1 loci, in particular, have near-maximum departures from the neutrality model, which suggests that balancing selection has been especially strong in these cases. Several novel DQA1-DQB1 haplotypes and the discovery of a new DRB1 allele demonstrate an evolutionary tendency favoring the diversification of class II alleles and haplotypes. The recombination interval between the centromeric DPB1 locus and the other class II loci will, in the absence of other forces such as selection, reduce disequilibrium across this region. However, nearly all common alleles were found to be part of DR-DP haplotypes in strong disequilibrium, consistent with the recent action of selection acting on these haplotypes in the Cayapa. 50 refs., 3 figs., 3 tabs.

Use of PCR with Sequence-specific Primers for High-Resolution Human Leukocyte Antigen Typing of Patients with Narcolepsy

Science.gov (United States)

Woo, Hye In; Joo, Eun Yeon; Lee, Kyung Wha

2012-01-01

Background Narcolepsy is a neurologic disorder characterized by excessive daytime sleepiness, symptoms of abnormal rapid eye movement (REM) sleep, and a strong association with HLA-DRB1*1501, -DQA1*0102, and -DQB1*0602. Here, we investigated the clinico-physical characteristics of Korean patients with narcolepsy, their HLA types, and the clinical utility of high-resolution PCR with sequence-specific primers (PCR-SSP) as a simple typing method for identifying DRB1*15/16, DQA1, and DQB1 alleles. Methods The study population consisted of 67 consecutively enrolled patients having unexplained daytime sleepiness and diagnosed narcolepsy based on clinical and neurological findings. Clinical data and the results of the multiple sleep latency test and polysomnography were reviewed, and HLA typing was performed using both high-resolution PCR-SSP and sequence-based typing (SBT). Results The 44 narcolepsy patients with cataplexy displayed significantly higher frequencies of DRB1*1501 (Pc= 0.003), DQA1*0102 (Pc=0.001), and DQB1*0602 (Pc=0.014) than the patients without cataplexy. Among patients carrying DRB1*1501-DQB1*0602 or DQA1*0102, the frequencies of a mean REM sleep latency of less than 20 min in nocturnal polysomnography and clinical findings, including sleep paralysis and hypnagogic hallucination were significantly higher. SBT and PCR-SSP showed 100% concordance for high-resolution typing of DRB1*15/16 alleles and DQA1 and DQB1 loci. Conclusions The clinical characteristics and somnographic findings of narcolepsy patients were associated with specific HLA alleles, including DRB1*1501, DQA1*0102, and DQB1*0602. Application of high-resolution PCR-SSP, a reliable and simple method, for both allele- and locus-specific HLA typing of DRB1*15/16, DQA1, and DQB1 would be useful for characterizing clinical status among subjects with narcolepsy. PMID:22259780

HLA-haplotypes, anti- beta-cell antibodies: their role in prognostication of type 1 diabetes mellitus (results of 11-year observation

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Elena Vital'evna Titovich

2010-12-01

Full Text Available The risk of type 1 diabetes mellitus (DM1 depends in the first place on the presence of predetermining HLA DR haplotypes, DQ genes, and specific autoantibodies.Aim. Prospective observation of DM1 risk groups (healthy sibs of DM patients for the elucidation of the role of genetic and autoimmune abnormalities in thedevelopment of DM1. Materials and methods. Predetermining and protective haplotypes (HLA-DRBI, DQ genes in combination with immunological markers (autoantibodiesto cytoplasmic structures of betbeta-cells (ICA, anti-insulin autoantibodies (IAA, anti-glutamate decarboxylase autoantibodies (GAD were studied in healthysibs of mean age 11.9?5.8 years selected from 143 discordant families of patients with DM1. In addition, a random sample of 599 DM1 patients (mean age7.5?6.2 years was enrolled for molecular genetic studies (HLA-DRBI-DG genes. The control group comprised 200 subjects. Results. DQAI*0501-DQB1+0201 (DQ2 and DQAI*0301-DQBI*0302 (DG8 haplotype heterozygosity creating the highest risk of DM1, the healthy sibswere divided into 3 risk groups. The high risk group 1 (DQ2/DQ8 included 23 (13.5% subjects, moderate risk group 2 (DQ2/X, DQ8/X 85 (59.7%, andlow risk group 3 (X/X; X - any haplotype besides DQ2, DQ8 63 (36.8%. The frequency of autoantibodies (AB of 2 or 3 species in group 1 was higher thanin groups 2 and 3 (26.1, 14.1, 11.1% respectively, p>0.05; 8.7, 2.4, 0%, p

Role of a Novel Human Leukocyte Antigen-DQA1*01:02;DRB1*15:01 Mixed Isotype Heterodimer in the Pathogenesis of “Humanized” Multiple Sclerosis-like Disease*

Science.gov (United States)

Kaushansky, Nathali; Eisenstein, Miriam; Boura-Halfon, Sigalit; Hansen, Bjarke Endel; Nielsen, Claus Henrik; Milo, Ron; Zeilig, Gabriel; Lassmann, Hans; Altmann, Daniel M.; Ben-Nun, Avraham

2015-01-01

Gene-wide association and candidate gene studies indicate that the greatest effect on multiple sclerosis (MS) risk is driven by the HLA-DRB1*15:01 allele within the HLA-DR15 haplotype (HLA-DRB1*15:01-DQA1*01:02-DQB1*0602-DRB5*01:01). Nevertheless, linkage disequilibrium makes it difficult to define, without functional studies, whether the functionally relevant effect derives from DRB1*15:01 only, from its neighboring DQA1*01:02-DQB1*06:02 or DRB5*01:01 genes of HLA-DR15 haplotype, or from their combinations or epistatic interactions. Here, we analyzed the impact of the different HLA-DR15 haplotype alleles on disease susceptibility in a new “humanized” model of MS induced in HLA-transgenic (Tg) mice by human oligodendrocyte-specific protein (OSP)/claudin-11 (hOSP), one of the bona fide potential primary target antigens in MS. We show that the hOSP-associated MS-like disease is dominated by the DRB1*15:01 allele not only as the DRA1*01:01;DRB1*15:01 isotypic heterodimer but also, unexpectedly, as a functional DQA1*01:02;DRB1*15:01 mixed isotype heterodimer. The contribution of HLA-DQA1/DRB1 mixed isotype heterodimer to OSP pathogenesis was revealed in (DRB1*1501xDQB1*0602)F1 double-Tg mice immunized with hOSP(142–161) peptide, where the encephalitogenic potential of prevalent DRB1*1501/hOSP(142–161)-reactive Th1/Th17 cells is hindered due to a single amino acid difference in the OSP(142–161) region between humans and mice; this impedes binding of DRB1*1501 to the mouse OSP(142–161) epitope in the mouse CNS while exposing functional binding of mouse OSP(142–161) to DQA1*01:02;DRB1*15:01 mixed isotype heterodimer. This study, which shows for the first time a functional HLA-DQA1/DRB1 mixed isotype heterodimer and its potential association with disease susceptibility, provides a rationale for a potential effect on MS risk from DQA1*01:02 through functional DQA1*01:02;DRB1*15:01 antigen presentation. Furthermore, it highlights a potential contribution to MS

Study of Colombia North Wiwa El Encanto Amerindians HLA- genes: Pacific Islanders relatedness.

Science.gov (United States)

Arnaiz-Villena, Antonio; Palacio-Grüber, Jose; Juarez, Ignacio; Muñiz, Ester; Hernández, Ennio; Bayona, Brayan; Campos, Cristina; Nuñez, Jorge; Lopez-Nares, Adrian; Martin-Villa, Manuel; Silvera, Carlos

2018-07-01

We have studied Wiwa/Sanja Amerindians HLA-A, -B, -C, -DRB1 and DQB1 allele frequencies and extended haplotypes in 52 unrelated individuals from "El Encanto" town at Guanachaca riverside. High frequency alleles were in general present in other Amerindian populations. Also, three extended haplotypes and eight ones were respectively both "new found" and already described in Amerindians from North, Central and South America, including Lakota-Sioux, Mayas, Teeneks, Quechua and Aymaras. Analyses of HLA-A*24:02 and -C*01:02 Wiwa high frequency alleles suggested a specific relatedness with another Amerindian and Pacific Islander ethnic groups (these two particular alleles bearing in high frequencies); they include New Zealand Maoris, Taiwanese, Japanese, Papua New Guinea, and Samoans among others. This may indicate that selective forces are maintaining these two alleles high frequency within this wide American/Pacific area. Copyright © 2018. Published by Elsevier Inc.

Epidemiology of human leukocyte antigens among omani population.

Science.gov (United States)

Al Salmi, Issa; Metry, Abdul Massiah; Al Ismaili, Faisal; Hola, Alan; Shaheen, Faissal; Fakhoury, Hana; Hannawi, Suad

2017-01-01

Oman is located on the Southeastern coast of the Arabian Peninsula, and its population has high levels of consanguinity. Human leukocytic antigen (HLA) typing analysis in human population holds unexploited potential for elucidating the genetic causes of human disease and possibly leads to personalized medicine. This is a retrospective, descriptive study evaluating HLA frequencies of Omani individuals who underwent workup for kidney transplantation at the Royal Hospital (RH) from 2005 to 2016. Data on 870 subjects were collected from the Oman kidney transplant registry at RH as well from electronic medical record system. The mean age (standard deviation) years for the cohort were 33.2 (13.0). Males constituted 56.3% (490) while females constituted 43.7% (380). Seven HLA-A alleles accounted for more than 70% of the total alleles. Of which, HLA-A2 contributed the highest frequency (24%), followed by HLA A11 (9.4%), and A32 (8.1%). Ten alleles accounted for 70% of HLA-B alleles. Of which, HLA-B51 was the most common (18.9%), followed by HLA-B-35 (13.6%), and HLA-B8 (7.9%). Seven HLA-DRB1 alleles accounted for more than 70% of the total HLA DRB1 alleles, of which HLA- DRB1*16 contributed the highest frequency (29.56%). This was followed by HLA-DRB1*03 (14.57%) and HLA-DRB1*11 (9.48%). While three alleles accounted for more than 75% of the total HLA DQB1alleles. Of which, HLA-DQB1*05 contributed the highest frequency (37.56%). This was followed by allele HLA-DQB1*02 (26.48%) and HLA-DQB1*03 (17.18%). This study showed considerable heterogeneity in both HLA Class I and Class II antigens, which reflects admixture of our population with rest of old world countries. Despite the high levels of consanguinity, this population is genetically highly heterogeneous. These findings may be useful for transplantation programs, noncommunicable diseases, epidemiology of HLA linked diseases, pharmacogenomics, and anthropology.

Epidemiology of human leukocyte antigens among omani population

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Issa Al Salmi

2017-01-01

Full Text Available Oman is located on the Southeastern coast of the Arabian Peninsula, and its population has high levels of consanguinity. Human leukocytic antigen (HLA typing analysis in human population holds unexploited potential for elucidating the genetic causes of human disease and possibly leads to personalized medicine. This is a retrospective, descriptive study evaluating HLA frequencies of Omani individuals who underwent workup for kidney transplantation at the Royal Hospital (RH from 2005 to 2016. Data on 870 subjects were collected from the Oman kidney transplant registry at RH as well from electronic medical record system. The mean age (standard deviation years for the cohort were 33.2 (13.0. Males constituted 56.3% (490 while females constituted 43.7% (380. Seven HLA-A alleles accounted for more than 70% of the total alleles. Of which, HLA-A2 contributed the highest frequency (24%, followed by HLA A11 (9.4%, and A32 (8.1%. Ten alleles accounted for 70% of HLA-B alleles. Of which, HLA-B51 was the most common (18.9%, followed by HLA-B-35 (13.6%, and HLA-B8 (7.9%. Seven HLA-DRB1 alleles accounted for more than 70% of the total HLA DRB1 alleles, of which HLA- DRB1*16 contributed the highest frequency (29.56%. This was followed by HLA-DRB1*03 (14.57% and HLA-DRB1*11 (9.48%. While three alleles accounted for more than 75% of the total HLA DQB1alleles. Of which, HLA-DQB1*05 contributed the highest frequency (37.56%. This was followed by allele HLA-DQB1*02 (26.48% and HLA-DQB1*03 (17.18%. This study showed considerable heterogeneity in both HLA Class I and Class II antigens, which reflects admixture of our population with rest of old world countries. Despite the high levels of consanguinity, this population is genetically highly heterogeneous. These findings may be useful for transplantation programs, noncommunicable diseases, epidemiology of HLA linked diseases, pharmacogenomics, and anthropology.

Genome-Wide Analysis of Genetic Risk Factors for Rheumatic Heart Disease in Aboriginal Australians Provides Support for Pathogenic Molecular Mimicry.

Science.gov (United States)

Gray, Lesley-Ann; D'Antoine, Heather A; Tong, Steven Y C; McKinnon, Melita; Bessarab, Dawn; Brown, Ngiare; Reményi, Bo; Steer, Andrew; Syn, Genevieve; Blackwell, Jenefer M; Inouye, Michael; Carapetis, Jonathan R

2017-12-12

Rheumatic heart disease (RHD) after group A streptococcus (GAS) infections is heritable and prevalent in Indigenous populations. Molecular mimicry between human and GAS proteins triggers proinflammatory cardiac valve-reactive T cells. Genome-wide genetic analysis was undertaken in 1263 Aboriginal Australians (398 RHD cases; 865 controls). Single-nucleotide polymorphisms were genotyped using Illumina HumanCoreExome BeadChips. Direct typing and imputation was used to fine-map the human leukocyte antigen (HLA) region. Epitope binding affinities were mapped for human cross-reactive GAS proteins, including M5 and M6. The strongest genetic association was intronic to HLA-DQA1 (rs9272622; P = 1.86 × 10-7). Conditional analyses showed rs9272622 and/or DQA1*AA16 account for the HLA signal. HLA-DQA1*0101_DQB1*0503 (odds ratio [OR], 1.44; 95% confidence interval [CI], 1.09-1.90; P = 9.56 × 10-3) and HLA-DQA1*0103_DQB1*0601 (OR, 1.27; 95% CI, 1.07-1.52; P = 7.15 × 10-3) were risk haplotypes; HLA_DQA1*0301-DQB1*0402 (OR 0.30, 95%CI 0.14-0.65, P = 2.36 × 10-3) was protective. Human myosin cross-reactive N-terminal and B repeat epitopes of GAS M5/M6 bind with higher affinity to DQA1/DQB1 alpha/beta dimers for the 2-risk haplotypes than the protective haplotype. Variation at HLA_DQA1-DQB1 is the major genetic risk factor for RHD in Aboriginal Australians studied here. Cross-reactive epitopes bind with higher affinity to alpha/beta dimers formed by risk haplotypes, supporting molecular mimicry as the key mechanism of RHD pathogenesis. © The Author 2017. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.

Peptide immunisation of HLA-DR-transgenic mice permits the identification of a novel HLA-DRbeta1*0101- and HLA-DRbeta1*0401-restricted epitope from p53.

Science.gov (United States)

Rojas, José Manuel; McArdle, Stephanie E B; Horton, Roger B V; Bell, Matthew; Mian, Shahid; Li, Geng; Ali, Selman A; Rees, Robert C

2005-03-01

Because of the central role of CD4(+) T cells in antitumour immunity, the identification of the MHC class II-restricted peptides to which CD4(+) T cells respond has become a priority of tumour immunologists. Here, we describe a strategy permitting us to rapidly determine the immunogenicity of candidate HLA-DR-restricted peptides using peptide immunisation of HLA-DR-transgenic mice, followed by assessment of the response in vitro. This strategy was successfully applied to the reported haemaglutinin influenza peptide HA(307-319), and then extended to three candidate HLA-DR-restricted p53 peptides predicted by the evidence-based algorithm SYFPEITHI to bind to HLA-DRbeta1*0101 (HLA-DR1) and HLA-DRbeta1*0401 (HLA-DR4) molecules. One of these peptides, p53(108-122), consistently induced responses in HLA-DR1- and in HLA-DR4-transgenic mice. Moreover, this peptide was naturally processed by dendritic cells (DCs), and induced specific proliferation in the splenocytes of mice immunised with p53 cDNA, demonstrating that immune responses could be naturally mounted to the peptide. Furthermore, p53(108-122) peptide was also immunogenic in HLA-DR1 and HLA-DR4 healthy donors. Thus, the use of this transgenic model permitted the identification of a novel HLA-DR-restricted epitope from p53 and constitutes an attractive approach for the rapid identification of novel immunogenic MHC class II-restricted peptides from tumour antigens, which can ultimately be incorporated in immunotherapeutic protocols.

HLA DRB5*01 Association Survey with Multiple Sclerosis in Khuzestan Province of Iran

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Tahereh Latifi Pakdehi

2017-08-01

Full Text Available Background Multiple sclerosis is a potentially disabling disease of the brain and spinal cord (central nervous system (CNS. Although the cause of MS is currently unknown, both genetic and environmental factors have been shown to contribute to the pathogenesis of MS. The human leukocyte antigen (HLA class II alleles DRB1*1501, DRB5*0101, DQA1*0102, DQB1*0602 may have an important genetic effect. However, this is controversial in different population studies. Objectives The aim of this study was to investigate the correlation of HLA DRB5*01 with MS in Khuzestan province. Methods The present case-control study focused on HLA DRB5*01 association in 202 MS patients from Khuzestan. Seventy four point two five percent (74.25% of patients classified as relapsing-remitting and other patients were as primary-progressive, secondary progressive and progressive-relapsing MS. One hundred eighty seven persons that have no any inflammatory diseases investigated as control group. Polymerase chain reaction amplification method was performed to determine the type of HLA with sequence-specific primers (PCR-SSP. The frequencies of the mentioned allele were compared between the patients and control group using SPSS 21 statistical software and the chi square test. Results Twenty- seven point seven two percent (27.72% of patients and 21.39% from the control group were positive with this type of HLA. Conclusions This is the first study that investigate HLA DRB5*01 association with multiple sclerosis patients in Khuzestan. We found that there is no association between HLA DRB5*01 with multiple sclerosis in Khuzestan province (P = 0.148.

Analysis of HLA-A, HLA-B, HLA-DRB1 allelic, genotypic, and haplotypic frequencies in colombian population

OpenAIRE

Yazmin Rocío Árias-Murillo; Miguel Ángel Castro-Jiménez; María Fernanda Ríos-Espinosa; Juan Javier López-Rivera; Sandra Johanna Echeverry-Coral; Oscar Martínez-Nieto

2010-01-01

Introduction: The high polymorphism of the HLA system allows its typification to be used as valuable tool in establishing association to various illnesses, immune and genetic profiles; it also provides a guide to identifying compatibility among donors and receptors of organs transplants. Objective: To establish HLA-A, HLA-B, and HLA.DRB1 allele, genotype and haplotype frequencies among patients treated at Clinica Colsanitas SA. Methods: 561 patients coming from different regions in Col...

DNA polymorphism of HLA class II genes in systemic lupus erythematosus

DEFF Research Database (Denmark)

Cowland, J B; Andersen, V; Halberg, P

1994-01-01

We investigated the DNA restriction fragment length polymorphism (RFLP) of the major histocompatibility complex (MHC) genes: HLA-DRB, -DQA, -DQB, -DPB in 24 Danish patients with systemic lupus erythematosus (SLE) and in 102 healthy Danes. A highly significant increase of the frequency of the DR3......- and DRw6-associated 7.00 kb DRB TaqI DNA fragment was found in SLE patients compared to normal controls (83.3% vs 35.5%; RR = 9.1, p 1*0501-associated 4.56 kb DQA TaqI fragment and the DRB3*01/03-associated 9.79 kb TaqI fragment were also found to be significantly...... increased in SLE patients (70.8% vs 29.7%; RR = 5.8, p 1%; RR = 4.3, p

The involvement of HLA-DRBI, DQAI, DQBI and complement C4A Loci in diagnosing systemic lupus erythematosus among Tunisians

International Nuclear Information System (INIS)

Ayed, Khaled; Gorgi, Youser; Ayed-Jendoubi, Saloua; Bardi, Rafiqa

2004-01-01

Genetic susceptibility to systemetic lupus erythematosus (SLE) varies among populations. Few data exist on associations of HLA class II and class III allels of major histocompatibility complex (MHC) and susceptibility to SLE in Tunisians. We compared HLA-DRBI, DQAI, DQBI and C4 allotypes in 62 Tunisians SLE patients and 100 matched controls. We also assessed the association of specific allels with distinct autoantibody profiles in SLE patients. HLA-DRBI *0301, -DRBI*1501 and C4AQO allels were increased in the SLE patients, while the frequencies of HLA-DRBI*04 and DQBI*03 were decreased. HLA-DQA1*0102 and DQAI*0501 were significantly increased in the SLE patients. HLA-DQBI*0201 and and DQBI*0602 were more frequent in the SLE patients. C4A*QO and C4B*QO were increased in the frequency in the SLE patients compared to the controls, but only C4A null was significantly increased. 11 of 17 SLE patients with the C4 null allele were HLA-DRBI*0301 positive. 3 of the 16 SLE patients with HLA-DRBI*1501 were associated with the HLA-DQBI*0501 rather than DQBI*0602, as has been reported in European SLE patients. The MHC class II allels (DRBI, DQA1, DQB1)and C$ null assosiations noted in other ethnic groups are also found in Tunisians, suggesting shared suspectibility factors across ethnic lines in predisposition to SLE. In contrast to other ethnic groups, MHC class II allels are not associated with the presence of specific autoantibodies in Tunisians SLE patients. (author)

CYP21A2 polymorphisms in patients with autoimmune Addison's disease, and linkage disequilibrium to HLA risk alleles.

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Brønstad, Ingeborg; Skinningsrud, Beate; Bratland, Eirik; Løvås, Kristian; Undlien, Dag; Sverre Husebye, Eystein; Wolff, Anette Susanne Bøe

2014-12-01

Steroid 21-hydroxylase, encoded by CYP21A2, is the major autoantigen in autoimmune Addison's disease (AAD). CYP21A2 is located in the region of the HLA complex on chromosome 6p21.3, which harbours several risk alleles for AAD. The objective was to investigate whether CYP21A2 gene variants confer risk of AAD independently of other risk alleles in the HLA loci. DNA samples from 381 Norwegian patients with AAD and 340 healthy controls (HC) previously genotyped for the HLA-A, -B, -DRB1, and -DQB1 and MICA loci were used for genotyping of CYP21A2. Genotyping of CYP21A2 was carried out by direct sequencing. Linkage of CYP21A2 to the HLA loci was assessed using UNPHASED version 3.0.10 and PHASE version 2.1. Heterozygotes of the single-nucleotide polymorphisms (SNPs) rs397515394, rs6467, rs6474, rs76565726 and rs6473 were detected significantly more frequently in AAD patients compared with HC (P<0.005), but all SNPs were in a linkage disequilibrium (LD) with high-risk HLA-DRB1 haplotypes. rs6472C protected against AAD (odds ratio=0.15, 95% CI (0.08-0.30), P=3.8×10(-10)). This SNP was not in an LD with HLA loci (P=0.02), but did not increase protection when considering the effect of HLA-DRB1 alleles. Mutations causing congenital adrenal hyperplasia were found in heterozygosity in <1.5% of the cases in both groups. Genetic variants of CYP21A2 associated to AAD are in LD with the main AAD risk locus HLA-DRB1, and CYP21A2 does not constitute an independent susceptibility locus. © 2014 European Society of Endocrinology.

Targeting the Immunogenetic Diseases with the Appropriate HLA Molecular Typing: Critical Appraisal on 2666 Patients Typed in One Single Centre

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M. Guarene

2013-01-01

Full Text Available We compared the immunogenetic data from 2666 patients affected by HLA-related autoimmune diseases with those from 4389 ethnically matched controls (3157 cord blood donors CBD, 1232 adult bone marrow donors BMD, to verify the appropriateness of HLA typing requests received in the past decade. The frequency of HLA-B*27 phenotype was 10.50% in 724 ankylosing spondylitis, 16.80% in 125 uveitis (3.41% BMD, 4.24% CBD, P<0.0001; HLA-B*51 allele was 15.57% in 212 Behçet’s disease (12.91% BMD, 9.88% CBD, P<0.0001; the HLA-DRB1-rheumatoid arthritis (RA shared epitope was 13.72% in 554 RA (10.85% BMD, 13.48% CBD, P=0.016; the carriers of almost one of HLA-DQB1 susceptibility alleles were 84.91% in 795 celiac disease (CD and 59.37% in 256 insulin-dependent diabetes mellitus (IDDM (46.06% in 875 CBD, 42.75% in 662 BMD P<0.0001. Overall, our results show that the HLA marker frequencies were higher in patients than controls, but lower than expected from the literature data (excluding CD and IDDM and demonstrate that, in complex immunogenetic conditions, a substantial number of genetic analyses are redundant and inappropriate, burdening to the public health costs. For this reason, we suggest the Italian Scientific Society of Immunogenetics to establish guidelines to improve the appropriateness of typing requests.

HLA and skin cancer HLA e câncer de pele

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Renan Rangel Bonamigo

2012-02-01

Full Text Available Skin cancer - melanoma and non melanoma - are common neoplasm with rising incidence over the last decades. It is an important public health problem. Its pathogenesis is not completely understood and the same happens with the genetic factors involved. The genes that encode the HLA are associated with some tumors and they may be responsible for one of the mechanisms that take part in the development of the before mentioned cancers. We have reviewed the literature on the subject of HLA antigens, melanoma and non melanoma skin cancer.Os cânceres da pele - melanoma e não-melanoma - são neoplasias comuns e com incidência crescente ao longo de décadas. Representam um importante problema de saúde pública. A patogênese destas neoplasias não é completamente compreendida, assim como não o são os fatores genéticos envolvidos. Os genes HLA estão associados a alguns tumores e podem representar um dos mecanismos implicados no desenvolvimento do câncer de pele. Apresenta-se uma revisão atualizada sobre a relação entre antígenos HLA, câncer da pele não-melanoma e melanoma.

The Case for High Resolution Extended 6-Loci HLA Typing for Identifying Related Donors in the Indian Subcontinent.

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Agarwal, Rajat Kumar; Kumari, Ankita; Sedai, Amit; Parmar, Lalith; Dhanya, Rakesh; Faulkner, Lawrence

2017-09-01

Three-loci low-resolution (LR) or intermediate-resolution HLA typing is generally considered adequate in the related blood and marrow transplantation (BMT) context. However, a single high-resolution (HR) mismatch may have a similar adverse impact on BMT outcome as an LR one. We sought to determine the frequency of mismatches that may go undetected when standard typing (LR or 3-loci HR) is used compared with 6-loci HR typing for related donor compatibility testing, and to assess its impact on relevant BMT outcomes. We analyzed data from a total of 2554 6-loci (HLA-A, -B, -C, -DRB1, -DQB1, and -DPB1) HR sequence-based typing (full typing [FT]) from 754 patients, 1011 siblings, and 789 parents done at DKMS Germany (www.DKMS.de) between January 1, 2014, and June 21, 2016. We also studied 38 cases in which the family had undergone 3-loci HLA typing (standard typing [ST]). Patients were from India (70%), Pakistan (22%), and Sri Lanka (8%). The IMGT/HLA database (www.ebi.ac.uk/ipd/imgt/hla) was used to tease out nonpermissive DPB1 mismatches. HLA disparity-related outcomes, such as rejection and graft-versus-host disease (GVHD) were assessed in a retrospective matched-pair cohort of 50 patients (25 with ST and 25 with FT) who underwent BMT for severe thalassemia from compatible related donors. We found fully matched (either 12/12 HR matches or with a single permissive DPB1 mismatch) related donors for 285 patients (38%). Of these donors, 89% were siblings and 11% were parents. The likelihood of matching on an individual locus on LR but not on HR was found to be 5%. A total of 9 donors (3%; 7 siblings and 2 parents) who would have been considered a full match by HR typing on A, B, and DRB1 alone were not a match by extended 6-loci HR typing. Five of these 9 donors had a mismatch on C or DQB1, and 4 had a nonpermissive DPB1 mismatch. In this group, 5 donors (56%) belonged to a consanguineous family, in 2 donors (22%) there was no reported consanguinity, and in 2 donors (22

Origin of Bolivian Quechua Amerindians: their relationship with other American Indians and Asians according to HLA genes.

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Martinez-Laso, Jorge; Siles, Nancy; Moscoso, Juan; Zamora, Jorge; Serrano-Vela, Juan I; R-A-Cachafeiro, Juan I; Castro, Maria J; Serrano-Rios, Manuel; Arnaiz-Villena, Antonio

2006-01-01

The Incas were Quechua-speaking people who settled down near Cuzco (Peru). They had an empire ranging from Ecuador to Chile, when Spanish conquerors seized their kingdom around 1532 AD. Nowadays, Quechua-speaking people inhabits Colombia, Ecuador, Bolivia, Peru and Argentina; however, Quechua language was imposed by both Incas and Spaniards to many non-Quechua speaking communities. We have taken a sample of Quechuan Bolivian blood donors from La Paz (Titicaca Lake region) where Inca-Quechuas themselves believed that came from. This group was compared with 6892 individuals from 68 different world populations regarding HLA/DNA allele frequencies distribution. Genetic distances, dendrograms and correspondence analyses were carried out in order to establish relationships among populations. The main conclusions are: (1) DRB1 and -DQB1 haplotypes shared with Asians are found in Quechuas and are not observed in other (Mesoamerican) Amerindians. (2) Aymara-speaking people from the same Titicaca Lake (La Paz) area shows close genetic distances with Quechuas in one dimension results (genetic distances); however, their HLA gene frequency distribution differs according to Neighbor-Joining (NJ) trees and correspondence analysis (multidimensional and more reliable analyses). Also, the common high frequency Asian and Athabascan HLA-DRB1*0901 allele is found in Quechuas in a significant frequency. Quechuas are clearly included within the Amerindian group.

The Type 1 Diabetes - HLA Susceptibility Interactome - Identification of HLA Genotype-Specific Disease Genes for Type 1 Diabetes

DEFF Research Database (Denmark)

Brorsson, C.; Hansen, Niclas Tue; Bergholdt, R.

2010-01-01

Background: The individual contribution of genes in the HLA region to the risk of developing type 1 diabetes (T1D) is confounded by the high linkage disequilibrium (LD) in this region. Using a novel approach we have combined genetic association data with information on functional protein......-protein interactions to elucidate risk independent of LD and to place the genetic association into a functional context. Methodology/Principal Findings: Genetic association data from 2300 single nucleotide polymorphisms (SNPs) in the HLA region was analysed in 2200 T1D family trios divided into six risk groups based...... on HLA-DRB1 genotypes. The best SNP signal in each gene was mapped to proteins in a human protein interaction network and their significance of clustering in functional network modules was evaluated. The significant network modules identified through this approach differed between the six HLA risk groups...

Gradiente de riesgo genético HLA-DQ para diabetes tipo 1 y enfermedad celíaca en el noroeste de México

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M.E. Mejía-León

2015-04-01

Conclusión: Los sonorenses tienen una distribución de alelos HLA-DQ distintiva debido a su ascendencia. Las combinaciones del HLA-DQ8 con DQ2 o uno de sus alelos confirieron el máximo riesgo para ambas enfermedades. La DT1 y EC frecuentemente se presentan juntas.

Panuveíte em artrite indiferenciada HLA-B27 positiva Panuveitis in HLA-B27 positive undifferentiated arthritis

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Mário Sérgio Ferreira Santos

2008-10-01

Full Text Available Entre os vários tipos de inflamação ocular associados às doenças reumatológicas, a uveíte anterior é particularmente comum nas espondiloartropatias, em especial quando associada à presença do genótipo HLA-B27. Relatou-se o caso de um paciente com artrite indiferenciada HLA-B27 positivo, complicado com panuveíte e vasculite da retina, refratária ao tratamento imunossupressor tradicional, que obteve boa resposta clínica ao uso de anti-TNF-alfa.Among the several types of ocular inflammation associated to the rheumatic diseases, anterior uveitis is particularly common in the spondyloarthropathies, especially when associated to the presence of the HLA-B27 genotype. We report the case of HLA-B27 positive patient with undifferentiated arthritis, complicated with panuveitis and retinal vasculitis, that was refractory to the traditional imunossupressive treatment, and had a good clinical response with anti-TNF-alpha therapy.

Genetic differences between mestizo populations of Bolivia and Peru

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2003-01-01

plus grand assortiment de type caucasien chez les métisses péruviens rapportés dans la littérature. Ces découvertes pourraient avoir un impact en ce qui concerne l’efficacité de moyens d’immunisation modernes grâce aux vaccins d'ADN sur la population andine, et aussi en ce qui concerne l’identification de groupes à risque pour certaines conditions médicales. DIFERENCIAS GENÉTICAS ENTRE POBLACIONES MESTIZAS DE BOLIVIA Y PERÚ. Existe escasa información acerca del fondo genético de las poblaciones de Perú y Bolivia. Estudios han mostrado que los mestizos presentan varios alelos del sistema mayor de histocompatibilidad originalmente descritos en tribus amerindias genéticamente aisladas, y que los mestizos de Perú y Bolivia están genéticamente cercanamente relacionados. Mediante la técnica de transferencia de línea reversa, se realizó la tipificación de alelos de histocompatibilidad de Clase I (HLA-A, HLA-B, HLA-Cw así como de Clase II (HLA-DRB1 y HLA-DQB1 en 57 mestizos bolivianos. Los sujetos provinieron mayormente de La Paz (la ciudad principal en los Andes Bolivianos, además de otras tres ciudades importantes situadas en el Valle Central Boliviano (Sucre, Tarija y Tupiza. La comparación de la frecuencia de los alelos de los mestizos bolivianos con datos disponibles de la literatura acerca de mestizos peruanos, reveló que los alelos de Clase I HLA-Cw*01, y B*40 se encontraban en mayor proporción en el grupo de mestizos peruanos (Chi-cuadrado = 4.87 p<0,05 y chi-cuadrado = 7,56 p<0,01 respectivamente. Con respecto a los alelos de clase II, HLA-DRB1*1101 y DRB1*1302 se encontraron en mayor frecuencia en los mestizos peruanos (Chi-cuad = 5,12 p<.05 y chi-cuad = 3,8 p = 0.05 respectivamente, mientras que el alelo HLA-DQB1*0402 fue significativamente mayor en los mestizos bolivianos (Chi-cuad = 47,2 p<.0001. Las diferencias en las frecuencias de alelos encontradas, y la ausencia o presencia de algunos alelos en cualesquiera de los grupos, puede

Deciphering the fine nucleotide diversity of full HLA class I and class II genes in a well-documented population from sub-Saharan Africa.

Science.gov (United States)

Goeury, T; Creary, L E; Brunet, L; Galan, M; Pasquier, M; Kervaire, B; Langaney, A; Tiercy, J-M; Fernández-Viña, M A; Nunes, J M; Sanchez-Mazas, A

2018-01-01

With the aim to understand how next-generation sequencing (NGS) improves both our assessment of genetic variation within populations and our knowledge on HLA molecular evolution, we sequenced and analysed 8 HLA loci in a well-documented population from sub-Saharan Africa (Mandenka). The results of full-gene NGS-MiSeq sequencing compared with those obtained by traditional typing techniques or limited sequencing strategies showed that segregating sites located outside exon 2 are crucial to describe not only class I but also class II population diversity. A comprehensive analysis of exons 2, 3, 4 and 5 nucleotide diversity at the 8 HLA loci revealed remarkable differences among these gene regions, notably a greater variation concentrated in the antigen recognition sites of class I exons 3 and some class II exons 2, likely associated with their peptide-presentation function, a lower diversity of HLA-C exon 3, possibly related to its role as a KIR ligand, and a peculiar molecular diversity of HLA-A exon 2, revealing demographic signals. Based on full-length HLA sequences, we also propose that the most frequent DRB1 allele in the studied population, DRB1*13:04, emerged from an allelic conversion involving 3 potential alleles as donors and DRB1*11:02:01 as recipient. Finally, our analysis revealed a high occurrence of the DRB1*13:04-DQA1*05:05:01-DQB1*03:19 haplotype, possibly resulting from a selective sweep due to protection to Onchorcerca volvulus, a prevalent pathogen in West Africa. This study unveils highly relevant information on the molecular evolution of HLA genes in relation to their immune function, calling for similar analyses in other populations living in contrasting environments. © 2017 The Authors HLA: Immune Response Genetics Published by John Wiley & Sons Ltd.

Homozygous HLA-C1 is Associated with Reduced Risk of Relapse after HLA-Matched Transplantation in Patients with Myeloid Leukemia.

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Arima, Nobuyoshi; Kanda, Junya; Tanaka, Junji; Yabe, Toshio; Morishima, Yasuo; Kim, Sung-Won; Najima, Yuho; Ozawa, Yukiyasu; Eto, Tetsuya; Kanamori, Heiwa; Mori, Takehiko; Kobayashi, Naoki; Kondo, Tadakazu; Nakamae, Hirohisa; Uchida, Naoyuki; Inoue, Masami; Fukuda, Takahiro; Ichinohe, Tatsuo; Atsuta, Yoshiko; Kanda, Yoshinobu

2018-04-01

Natural killer (NK) cells assume graft-versus-leukemia alloreactivity after hematopoietic stem cell transplantation (HSCT) through their inhibitory killer cell immunoglobulin-like receptors (KIRs). KIR2D family members recognize HLA-C alleles with Asn80 (HLA-C1) or Lys80 (HLA-C2). The predominance of HLA-C1 over HLA-C2 and the frequent presence of KIR2DL1 are characteristic of Japanese people. We compared clinical outcomes among homozygous HLA-C1 (HLA-C1/C1) patients and heterozygous HLA-C1/C2 patients who underwent HLA-matched HSCT for hematologic malignancies by assessing the data of 10,638 patients from the Japanese national registry. HLA-C1/C1 recipients had a lower rate of relapse than HLA-C1/C2 recipients after transplantation for acute myelogenous leukemia (AML) (hazard ratio [HR], .79; P = .006) and chronic myelogenous leukemia (CML) (HR, .48; P = .025), but not for acute lymphoblastic leukemia (HR, 1.36), lymphoma (HR, .97), or low-grade myelodysplastic syndrome (HR, 1.40). We then grouped AML and CML patients together and divided them into several subgroups. Advantages of HLA-C1/C1 recipients over HLA-C1/C2 recipients regarding relapse were observed irrespective of donor relation (related: HR, .79, P = .069; unrelated: HR, .77, P = .022), preparative regimen (myeloablative: HR, .79, P = .014; reduced intensity: HR, .73, P = .084), and occurrence of acute graft-versus-host disease (yes: HR, .70, P = .122; no, HR .71, P = .026) or cytomegalovirus reactivation (reactivated: HR .67,P = .054; nonreactivated: HR .71, P = .033); however, these advantages were not observed in recipients with a delay in achieving complete chimerism (HR, 1.06). The advantage of decreasing relapse and extending relapse-free survival of C1/1 over C1/2 KIR-ligand status was most pronounced in T cell-depleted HSCT (HR, .27; P < .001 and HR, .30; P = .002, respectively) and in children age <15 years (HR, .29; P < .001 and HR .31; P�

HLA class I-mediated control of HIV-1 in the Japanese population, in which the protective HLA-B*57 and HLA-B*27 alleles are absent.

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Naruto, Takuya; Gatanaga, Hiroyuki; Nelson, George; Sakai, Keiko; Carrington, Mary; Oka, Shinichi; Takiguchi, Masafumi

2012-10-01

We investigated the effect of HLA class I alleles on clinical parameters for HIV-1 disease progression in the Japanese population, where two strongly protective alleles, HLA-B*57 and HLA-B*27, are virtually nonexistent. HLA-B alleles showed a dominant role, primarily through HLA-B*67:01 and the HLA-B*52:01-C*12:02 haplotype. Neither a rare-allele nor a heterozygote advantage was found, suggesting that the effect of HLA alleles in the Japanese population is either different from those observed in Africans and Caucasians or undetectable due to limited power.

A comparative review of HLA associations with hepatitis B and C viral infections across global populations

Institute of Scientific and Technical Information of China (English)

Rashmi Singh; Rashmi Kaul; Anil Kaul; Khalid Khan

2007-01-01

Hepatitis B (HBV) and hepatitis C (HCV) viral infection or co-infection leads to risk of development of chronic infection, cirrhosis and hepatocellular carcinoma (HCC). Immigration and globalization have added to the challenges of public health concerns regarding chronic HBV and HCV infections worldwide. The aim of this study is to review existing global literature across ethnic populations on HBV and HCV related human leukocyte antigen (HLA) associations in relation to susceptibility, viral persistence and treatment. Extensive literature search was conducted to explore the HLA associations in HBV and HCV infections reported across global populations over the past decade to understand the knowledge status, weaknesses and strengths of this information in different ethnic populations. HLA DR13 is consistently associated with HBV clearance globally. HLADRB1*11/*12 alleles and DQB1*0301 are associated with HBV persistence but with HCV clearance worldwide. Consistent association of DRB1*03 and *07 is observed with HCV susceptibility and non-responsiveness to HBV vaccination across the population. HLA DR13 is protective for vertical HBV and HCV transmission in Chinese and Italian neonates, but different alleles are associated with their susceptibility in these populations. HLA class I molecule interactions with Killer cell immunoglobulin like receptors (KIR) of natural killer (NK) cells modulate HCV infection outcome via regulating immune regulatory cells and molecules. HLA associations with HBV vaccination, interferon therapy in HBV and HCV, and with extra hepatic manifestations of viral hepatitis are also discussed. Systematic studies in compliance with global regulatory standards are required to identify the HLA specific viral epitope, stage specific T cell populations interacting with different HLA alleles during disease progression and viral clearance ofchronic HBV or HCV infections among different ethnic populations. These studies would facilitate stage specific

Positive selection on MHC class II DRB and DQB genes in the bank vole (Myodes glareolus).

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Scherman, Kristin; Råberg, Lars; Westerdahl, Helena

2014-05-01

The major histocompatibility complex (MHC) class IIB genes show considerable sequence similarity between loci. The MHC class II DQB and DRB genes are known to exhibit a high level of polymorphism, most likely maintained by parasite-mediated selection. Studies of the MHC in wild rodents have focused on DRB, whilst DQB has been given much less attention. Here, we characterised DQB genes in Swedish bank voles Myodes glareolus, using full-length transcripts. We then designed primers that specifically amplify exon 2 from DRB (202 bp) and DQB (205 bp) and investigated molecular signatures of natural selection on DRB and DQB alleles. The presence of two separate gene clusters was confirmed using BLASTN and phylogenetic analysis, where our seven transcripts clustered according to either DQB or DRB homologues. These gene clusters were again confirmed on exon 2 data from 454-amplicon sequencing. Our DRB primers amplify a similar number of alleles per individual as previously published DRB primers, though our reads are longer. Traditional d N/d S analyses of DRB sequences in the bank vole have not found a conclusive signal of positive selection. Using a more advanced substitution model (the Kumar method) we found positive selection in the peptide binding region (PBR) of both DRB and DQB genes. Maximum likelihood models of codon substitutions detected positively selected sites located in the PBR of both DQB and DRB. Interestingly, these analyses detected at least twice as many positively selected sites in DQB than DRB, suggesting that DQB has been under stronger positive selection than DRB over evolutionary time.

Imputing Variants in HLA-DR Beta Genes Reveals That HLA-DRB1 Is Solely Associated with Rheumatoid Arthritis and Systemic Lupus Erythematosus.

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Kwangwoo Kim

Full Text Available The genetic association of HLA-DRB1 with rheumatoid arthritis (RA and systemic lupus erythematosus (SLE is well documented, but association with other HLA-DR beta genes (HLA-DRB3, HLA-DRB4 and HLA-DRB5 has not been thoroughly studied, despite their similar functions and chromosomal positions. We examined variants in all functional HLA-DR beta genes in RA and SLE patients and controls, down to the amino-acid level, to better understand disease association with the HLA-DR locus. To this end, we improved an existing HLA reference panel to impute variants in all protein-coding HLA-DR beta genes. Using the reference panel, HLA variants were inferred from high-density SNP data of 9,271 RA-control subjects and 5,342 SLE-control subjects. Disease association tests were performed by logistic regression and log-likelihood ratio tests. After imputation using the newly constructed HLA reference panel and statistical analysis, we observed that HLA-DRB1 variants better accounted for the association between MHC and susceptibility to RA and SLE than did the other three HLA-DRB variants. Moreover, there were no secondary effects in HLA-DRB3, HLA-DRB4, or HLA-DRB5 in RA or SLE. Of all the HLA-DR beta chain paralogs, those encoded by HLA-DRB1 solely or dominantly influence susceptibility to RA and SLE.

MHC class II DQB diversity in the Japanese black bear, Ursus thibetanus japonicus

Science.gov (United States)

2012-01-01

Background The major histocompatibility complex (MHC) genes are one of the most important genetic systems in the vertebrate immune response. The diversity of MHC genes may directly influence the survival of individuals against infectious disease. However, there has been no investigation of MHC diversity in the Asiatic black bear (Ursus thibetanus). Here, we analyzed 270-bp nucleotide sequences of the entire exon 2 region of the MHC DQB gene by using 188 samples from the Japanese black bear (Ursus thibetanus japonicus) from 12 local populations. Results Among 185 of 188 samples, we identified 44 MHC variants that encoded 31 different amino acid sequences (allotypes) and one putative pseudogene. The phylogenetic analysis suggests that MHC variants detected from the Japanese black bear are derived from the DQB locus. One of the 31 DQB allotypes, Urth-DQB*01, was found to be common to all local populations. Moreover, this allotype was shared between the black bear on the Asian continent and the Japanese black bear, suggesting that Urth-DQB*01 might have been maintained in the ancestral black bear population for at least 300,000 years. Our findings, from calculating the ratio of non-synonymous to synonymous substitutions, indicate that balancing selection has maintained genetic variation of peptide-binding residues at the DQB locus of the Japanese black bear. From examination of genotype frequencies among local populations, we observed a considerably lower level of observed heterozygosity than expected. Conclusions The low level of observed heterozygosity suggests that genetic drift reduced DQB diversity in the Japanese black bear due to a bottleneck event at the population or species level. The decline of DQB diversity might have been accelerated by the loss of rare variants that have been maintained by negative frequency-dependent selection. Nevertheless, DQB diversity of the black bear appears to be relatively high compared with some other endangered mammalian

MHC class II DQB diversity in the Japanese black bear, Ursus thibetanus japonicus

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Yasukochi Yoshiki

2012-11-01

Full Text Available Abstract Background The major histocompatibility complex (MHC genes are one of the most important genetic systems in the vertebrate immune response. The diversity of MHC genes may directly influence the survival of individuals against infectious disease. However, there has been no investigation of MHC diversity in the Asiatic black bear (Ursus thibetanus. Here, we analyzed 270-bp nucleotide sequences of the entire exon 2 region of the MHC DQB gene by using 188 samples from the Japanese black bear (Ursus thibetanus japonicus from 12 local populations. Results Among 185 of 188 samples, we identified 44 MHC variants that encoded 31 different amino acid sequences (allotypes and one putative pseudogene. The phylogenetic analysis suggests that MHC variants detected from the Japanese black bear are derived from the DQB locus. One of the 31 DQB allotypes, Urth-DQB*01, was found to be common to all local populations. Moreover, this allotype was shared between the black bear on the Asian continent and the Japanese black bear, suggesting that Urth-DQB*01 might have been maintained in the ancestral black bear population for at least 300,000 years. Our findings, from calculating the ratio of non-synonymous to synonymous substitutions, indicate that balancing selection has maintained genetic variation of peptide-binding residues at the DQB locus of the Japanese black bear. From examination of genotype frequencies among local populations, we observed a considerably lower level of observed heterozygosity than expected. Conclusions The low level of observed heterozygosity suggests that genetic drift reduced DQB diversity in the Japanese black bear due to a bottleneck event at the population or species level. The decline of DQB diversity might have been accelerated by the loss of rare variants that have been maintained by negative frequency-dependent selection. Nevertheless, DQB diversity of the black bear appears to be relatively high compared with some other

MHC class II DQB diversity in the Japanese black bear, Ursus thibetanus japonicus.

Science.gov (United States)

Yasukochi, Yoshiki; Kurosaki, Toshifumi; Yoneda, Masaaki; Koike, Hiroko; Satta, Yoko

2012-11-29

The major histocompatibility complex (MHC) genes are one of the most important genetic systems in the vertebrate immune response. The diversity of MHC genes may directly influence the survival of individuals against infectious disease. However, there has been no investigation of MHC diversity in the Asiatic black bear (Ursus thibetanus). Here, we analyzed 270-bp nucleotide sequences of the entire exon 2 region of the MHC DQB gene by using 188 samples from the Japanese black bear (Ursus thibetanus japonicus) from 12 local populations. Among 185 of 188 samples, we identified 44 MHC variants that encoded 31 different amino acid sequences (allotypes) and one putative pseudogene. The phylogenetic analysis suggests that MHC variants detected from the Japanese black bear are derived from the DQB locus. One of the 31 DQB allotypes, Urth-DQB*01, was found to be common to all local populations. Moreover, this allotype was shared between the black bear on the Asian continent and the Japanese black bear, suggesting that Urth-DQB*01 might have been maintained in the ancestral black bear population for at least 300,000 years. Our findings, from calculating the ratio of non-synonymous to synonymous substitutions, indicate that balancing selection has maintained genetic variation of peptide-binding residues at the DQB locus of the Japanese black bear. From examination of genotype frequencies among local populations, we observed a considerably lower level of observed heterozygosity than expected. The low level of observed heterozygosity suggests that genetic drift reduced DQB diversity in the Japanese black bear due to a bottleneck event at the population or species level. The decline of DQB diversity might have been accelerated by the loss of rare variants that have been maintained by negative frequency-dependent selection. Nevertheless, DQB diversity of the black bear appears to be relatively high compared with some other endangered mammalian species. This result suggests that

The Protective Role of HLA-DRB1∗13 in Autoimmune Diseases

Science.gov (United States)

Bettencourt, Andreia; Carvalho, Cláudia; Leal, Bárbara; Brás, Sandra; Lopes, Dina; Martins da Silva, Ana; Santos, Ernestina; Torres, Tiago; Almeida, Isabel; Farinha, Fátima; Barbosa, Paulo; Marinho, António; Selores, Manuela; Correia, João; Vasconcelos, Carlos; Costa, Paulo P.; da Silva, Berta Martins

2015-01-01

Autoimmune diseases (AIDs) are characterized by a multifactorial aetiology and a complex genetic background, with the MHC region playing a major role. We genotyped for HLA-DRB1 locus 1228 patients with AIDs-213 with Systemic Lupus Erythematosus (SLE), 166 with Psoriasis or Psoriatic Arthritis (Ps + PsA), 153 with Rheumatoid Arthritis (RA), 67 with Systemic Sclerosis (SSc), 536 with Multiple Sclerosis (MS), and 93 with Myasthenia Gravis (MG) and 282 unrelated controls. We confirmed previously established associations of HLA-DRB1∗15 (OR = 2.17) and HLA-DRB1∗03 (OR = 1.81) alleles with MS, HLA-DRB1∗03 with SLE (OR = 2.49), HLA-DRB1∗01 (OR = 1.79) and HLA-DRB1∗04 (OR = 2.81) with RA, HLA-DRB1∗07 with Ps + PsA (OR = 1.79), HLA-DRB1∗01 (OR = 2.28) and HLA-DRB1∗08 (OR = 3.01) with SSc, and HLA-DRB1∗03 with MG (OR = 2.98). We further observed a consistent negative association of HLA-DRB1∗13 allele with SLE, Ps + PsA, RA, and SSc (18.3%, 19.3%, 16.3%, and 11.9%, resp., versus 29.8% in controls). HLA-DRB1∗13 frequency in the AIDs group was 20.0% (OR = 0.58). Although different alleles were associated with particular AIDs, the same allele, HLA-DRB1∗13, was underrepresented in all of the six diseases analysed. This observation suggests that this allele may confer protection for AIDs, particularly for systemic and rheumatic disease. The protective effect of HLA-DRB1∗13 could be explained by a more proficient antigen presentation by these molecules, favouring efficient clonal deletion during thymic selection. PMID:26605347

Intravenous immunoglobulin treatment and screening for hypocretin neuron-specific autoantibodies in recent onset childhood narcolepsy with cataplexy

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Knudsen, S; Mikkelsen, J D; Bang, B

2010-01-01

Narcolepsy with cataplexy (NC) is caused by substantial loss of hypocretin neurons. NC patients carry the HLA-DQB1*0602 allele suggesting that hypocretin neuron loss is due to an autoimmune attack. We tested intravenous immunoglobulin (IVIG) treatment in early onset NC.......Narcolepsy with cataplexy (NC) is caused by substantial loss of hypocretin neurons. NC patients carry the HLA-DQB1*0602 allele suggesting that hypocretin neuron loss is due to an autoimmune attack. We tested intravenous immunoglobulin (IVIG) treatment in early onset NC....

Analysis of Hypoxic and Hypercapnic Ventilatory Response in Healthy Volunteers.

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Shmuel Goldberg

Full Text Available A previous study has suggested that the Human Leukocyte Antigen (HLA allele DQB1*06:02 affects hypoxic ventilatory response (HVR but not hypercapnic ventilatory response (HCVR in an Asian population. The current study evaluated the relationship in Caucasians and Asians. In addition we assessed whether gender or polymorphisms in genes participating in the control of breathing affect HVR and HCVR.A re-breathing system was used to measure HVR and HCVR in 551 young adults (56.8% Caucasians, 30% Asians. HLA-DQB1*06:02 and tagged polymorphisms and coding variants in genes participating in breathing (PHOX2B, GPR4 and TASK2/KCNK5 were analyzed. The associations between HVR/HCVR and HLA-DQB1*06:02, genetic polymorphisms, and gender were evaluated using ANOVA or frequentist association testing with SNPTEST.HVR and gender are strongly correlated. HCVR and gender are not. Mean HVR in women was 0.276±0.168 (liter/minute/%SpO2 compared to 0.429±0.266 (liter/minute/%SpO2 in men, p<0.001 (55.4% higher HVR in men. Women had lower baseline minute ventilation (8.08±2.36 l/m vs. 10.00±3.43l/m, p<0.001, higher SpO2 (98.0±1.3% vs. 96.6±1.7%, p<0.001, and lower EtCO2 (4.65±0.68% vs. 4.82±1.02%, p = 0.025. One hundred and two (18.5% of the participants had HLA-DQB1*06:02. No association was seen between HLA-DQB1*06:02 and HVR or HCVR. Genetic analysis revealed point wise, uncorrected significant associations between two TASK2/KCNK5 variants (rs2815118 and rs150380866 and HCVR.This is the largest study to date reporting the relationship between gender and HVR/ HCVR and the first study assessing the association between genetic polymorphisms in humans and HVR/HCVR. The data suggest that gender has a large effect on hypoxic breathing response.

Association of HLA-A*02:06 and HLA-DRB1*04:05 with clinical subtypes of juvenile idiopathic arthritis.

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Yanagimachi, Masakatsu; Miyamae, Takako; Naruto, Takuya; Hara, Takuma; Kikuchi, Masako; Hara, Ryoki; Imagawa, Tomoyuki; Mori, Masaaki; Kaneko, Tetsuji; Goto, Hiroaki; Morita, Satoshi; Mizuki, Nobuhisa; Kimura, Akinori; Yokota, Shumpei

2011-03-01

Juvenile idiopathic arthritis (JIA) is one of the most common forms of pediatric chronic arthritis. JIA is a clinically heterogeneous disease. Therefore, the genetic background of JIA may also be heterogeneous. The aim of this study was to investigate associations between human leukocyte antigen (HLA) and susceptibility to JIA and/or uveitis, which is one of the most devastating complications of JIA. A total of 106 Japanese articular JIA patients (67 with polyarthritis and 39 with oligoarthritis) and 678 healthy controls were genotyped for HLA-A, -B and -DRB1 by PCR-sequence-specific oligonucleotide probe methodology. HLA-A(*)02:06 was the risk factor for JIA accompanied by uveitis after adjustment for clinical factors (corrected P-value < 0.001, odds ratio (OR) 11.7, 95% confidence interval (CI) 3.2-43.0). On the other hand, HLA-DRB1(*)04:05 was associated with polyarticular JIA (corrected P-value < 0.001, OR 2.9, 95% CI 1.7-4.8). We found an association of HLA-A(*)02:06 with susceptibility to JIA accompanied by uveitis, which might be considered a separate clinical JIA entity. We also found an association between HLA-DRB1(*)04:05 and polyarticular JIA. Thus, clinical subtypes of JIA can be classified by the presence of the specific HLA alleles, HLA-A(*)02:06 and DRB1(*)04:05.

Role of HLA-G1 in trophoblast cell proliferation, adhesion and invasion

International Nuclear Information System (INIS)

Jiang, Feng; Zhao, Hongxi; Wang, Li; Guo, Xinyu; Wang, Xiaohong; Yin, Guowu; Hu, Yunsheng; Li, Yi; Yao, Yuanqing

2015-01-01

Trophoblast cells are important in embryo implantation and fetomaternal tolerance. HLA-G is specifically expressed at the maternal–fetal interface and is a regulator in pregnancy. The aim of the present study was to detect the effect of HLA-G1 on trophoblast cell proliferation, adhesion, and invasion. Human trophoblast cell lines (JAR and HTR-8/SVneo cells) were infected with HLA-G1-expressing lentivirus. After infection, HLA-G1 expression of the cells was detected by western blotting. Cell proliferation was detected by the BrdU assay. The cell cycle and apoptosis of JAR and HTR-8/SVneo cells was measured by flow cytometry (FCM). The invasion of the cells under different conditions was detected by the transwell invasion chamber assay. HLA-G1 didn't show any significant influence on the proliferation, apoptosis, adhesion, and invasion of trophocytes in normal culture conditions. However, HLA-G1 inhibited JAR and HTR-8/SVneo cells invasion induced by hepatocyte growth factor (HGF) under normal oxygen conditions. In conditions of hypoxia, HLA-G1 couldn't inhibit the induction of cell invasion by HGF. HLA-G1 is not an independent factor for regulating the trophocytes. It may play an indirect role in embryo implantation and formation of the placenta. - Highlights: • HLA-G1 could not influence trophocytes under normal conditions. • HLA-G1 inhibited cell invasion induced by HGF under normal oxygen condition. • HLA-G1 could not influence cell invasion under hypoxia conditions

Role of HLA-G1 in trophoblast cell proliferation, adhesion and invasion

Energy Technology Data Exchange (ETDEWEB)

Jiang, Feng, E-mail: jiangfeng1161@163.com [Department of Gynecology and Obstetrics, Tangdu Hospital, The Fourth Military Medical University, 569 Xinsi Road, Baqiao District, Xi' an 710038 (China); Zhao, Hongxi [Department of Gynecology and Obstetrics, Tangdu Hospital, The Fourth Military Medical University, 569 Xinsi Road, Baqiao District, Xi' an 710038 (China); Wang, Li [Department of Gynecology and Obstetrics, The Chinese PLA General Hospital, 28 Fuxing Road, Haidian District, Beijing 100853 (China); Guo, Xinyu [Assisted Reproductive Center, General Hospital of Guangzhou Military Command, Guangzhou 510010 (China); Wang, Xiaohong; Yin, Guowu [Department of Gynecology and Obstetrics, Tangdu Hospital, The Fourth Military Medical University, 569 Xinsi Road, Baqiao District, Xi' an 710038 (China); Hu, Yunsheng [Department of Orthopedics, Tangdu Hospital, The Fourth Military Medical University, Xi' an 710038 (China); Li, Yi [Department of Gynecology and Obstetrics, Tangdu Hospital, The Fourth Military Medical University, 569 Xinsi Road, Baqiao District, Xi' an 710038 (China); Yao, Yuanqing, E-mail: yuanqingyaoxa@163.com [Department of Gynecology and Obstetrics, The Chinese PLA General Hospital, 28 Fuxing Road, Haidian District, Beijing 100853 (China)

2015-02-27

Trophoblast cells are important in embryo implantation and fetomaternal tolerance. HLA-G is specifically expressed at the maternal–fetal interface and is a regulator in pregnancy. The aim of the present study was to detect the effect of HLA-G1 on trophoblast cell proliferation, adhesion, and invasion. Human trophoblast cell lines (JAR and HTR-8/SVneo cells) were infected with HLA-G1-expressing lentivirus. After infection, HLA-G1 expression of the cells was detected by western blotting. Cell proliferation was detected by the BrdU assay. The cell cycle and apoptosis of JAR and HTR-8/SVneo cells was measured by flow cytometry (FCM). The invasion of the cells under different conditions was detected by the transwell invasion chamber assay. HLA-G1 didn't show any significant influence on the proliferation, apoptosis, adhesion, and invasion of trophocytes in normal culture conditions. However, HLA-G1 inhibited JAR and HTR-8/SVneo cells invasion induced by hepatocyte growth factor (HGF) under normal oxygen conditions. In conditions of hypoxia, HLA-G1 couldn't inhibit the induction of cell invasion by HGF. HLA-G1 is not an independent factor for regulating the trophocytes. It may play an indirect role in embryo implantation and formation of the placenta. - Highlights: • HLA-G1 could not influence trophocytes under normal conditions. • HLA-G1 inhibited cell invasion induced by HGF under normal oxygen condition. • HLA-G1 could not influence cell invasion under hypoxia conditions.

HLA Dr beta 1 alleles in Pakistani patients with rheumatoid arthritis

International Nuclear Information System (INIS)

Naqi, N.; Ahmed, T.A.; Bashir, M.M.

2011-01-01

Objective: To determine frequencies of HLA DR beta 1 alleles in rheumatoid arthritis in Pakistani patients. Study Design: Cross sectional / analytical study. Place and Duration of Study: Department of Immunology, Armed Forces Institute of Pathology, Rawalpindi in collaboration with Rheumatology departments of Military Hospital, Rawalpindi and Fauji Foundation Hospital, Rawalpindi, from January 2009 to January 2010. Methodology: HLA DR beta 1 genotyping of one hundred Pakistani patients, diagnosed as having RA as per American College of Rheumatology revised criteria 1987, was done. HLA DR beta 1 genotyping was carried out at allele group level (DR beta 1*01-DR beta 1*16) by sequence specific primers in RA patients. Comparison of HLA DR beta 1 allele frequencies between patients and control groups was made using Pearson's chi-square test to find possible association of HLA DR?1 alleles with RA in Pakistani rheumatoid patients. Results: HLA DR beta 1*04 was expressed with significantly increased frequency in patients with rheumatoid arthritis (p <0.05). HLA DR?1*11 was expressed statistically significantly more in control group as compared to rheumatoid patients indicating a possible protective effect. There was no statistically significant difference observed in frequencies of HLA DR beta 1 allele *01, DR beta 1 allele *03, DR beta 1 allele *07, DR beta 1 allele *08, DR beta 1 allele *09, DR beta 1 allele *10, DR beta 1 allele *12, DR beta 1 allele *13, DR beta 1 allele *14, DR?1 allele *15 and DR beta 1 allele *16 between patients and control groups. Conclusion: The identification of susceptible HLA DR beta 1 alleles in Pakistani RA patients may help physicians to make early decisions regarding initiation of early intensive therapy with disease modifying anti rheumatic medicines and biological agents decreasing disability in RA patients. (author)

Vitamin D effects on monocytes' CCL-2, IL6 and CD14 transcription in Addison's disease and HLA susceptibility.

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Kraus, A U; Penna-Martinez, M; Meyer, G; Badenhoop, K

2018-03-01

Addison's disease is a rare autoimmune disorder leading to adrenal insufficiency and life-long glucocorticoid dependency. Vitamin D receptor (VDR) polymorphisms and vitamin D deficiency predispose to Addison's disease. Aim of the current study was, to investigate potential anti-inflammatory vitamin D effects on monocytes in Addison's disease, focusing on inflammatory CCL-2 and IL6, as well on monocyte CD14 markers. Addison's disease is genetically linked to distinct HLA susceptibility alleles. Therefore we analyzed, whether HLA genotypes differed for vitamin D effects on monocyte markers. CD14 + monocytes were isolated from Addison's disease patients (AD, n=13) and healthy controls (HC, n=15) and stimulated with 1,25-dihydroxyvitamin D 3 and IL1β as an inflammatory stimulant. Cells were processed for mRNA expression of CCL-2, IL6 and CD14 and DNA samples were genotyped for major histocompatibility class (MHC) class II-encoded HLA- DQA1-DQB1 haplotypes. We found a downregulation of CCL-2 after vitamin D treatment in IL1β-stimulated monocytes both from AD patients and HC (AD p<0.001; HC p<0.0001). CD14 expression however, was upregulated in both HC and AD patients after vitamin D treatment (p<0.001, respectively). HC showed higher CD14 transcription level than AD patients after vitamin D treatment (p=0.04). Compared to IL1β-induced inflammation, HC have increased CD14 levels after vitamin D treatment (p<0.001), whereas the IL1β-induced CD14 expression of AD patients' monocytes did not change after vitamin D treatment (p=0.8). AD patients carrying HLA high-risk haplotypes showed an increased CCL-2 expression after IL1β-induced inflammation compared to intermediate-risk HLA carriers (p=0.05). Also HC monocytes' CD14 transcription after IL1β and vitamin D co-stimulation differed according to HLA risk profile. We show that vitamin D can exert anti-inflammatory effects on AD patients' monocytes which may be modulated by HLA risk genotypes. Copyright © 2017 Elsevier

[An evaluation of HLA class 2 alleles and anti-islet antibodies as evidence for non-autoimmune diabetes in Wolfram syndrome].

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Zmysłowska, Agnieszka; Borowiec, Maciej; Antosik, Karolina; Wyka, Krystyna; Cieślik-Heinrich, Agnieszka; Klich, Izabela; Młynarski, Wojciech

2010-01-01

A clinical criterion of the Wolfram syndrome is the coexistence of diabetes and optic atrophy recognized before the age of 15. Diabetes present in Wolfram syndrome is a result of the selective β cell loss and failed insulin secretion which is probably associated with non-autoimmune pathogenesis. The aim of the study was an evaluation of HLA subtypes and presence of β-cell autoantibodies in patients with molecularly confirmed Wolfram syndrome. 9 patients with Wolfram syndrome aged 10-24 years were examined. We also studied 218 patients with type 1 diabetes as a reference group. A control group of 176 healthy individuals was included in the study. Besides the clinical assessment the HLA typing by PCR-SSO was performed. Islet cell antibodies (ICA), antibodies to glutamic acid decarboxylase (GADA), thyrosine phosphatase antibodies (IA2A) and insulin antibodies (IAA) were also detected. In all nine patients the coexistence of diabetes with optic atrophy was observed and in 8/9 individuals additional symptoms were recognized. In patients with Wolfram syndrome a significantly lower age of diagnosis of diabetes (Me=5.0 years) than in type 1 diabetic children (Me=10.4; p=0.002) was observed. Studies of HLA subtypes demonstrated an increased prevalence of HLA-DQw1, DRB1⋅03 and/or 04 and DR2. A comparison of the frequency of the HLA alleles in patients with Wolfram syndrome with type 1 diabetic children showed a more frequent presence of the DRB1⋅1501 (p=0.03; OR=13.28 (2.44-72.12)) and DQB1⋅06 (p=0.016; OR=10.15 (2.49-41.35)) alleles in patients with Wolfram syndrome. Polish patients with Wolfram syndrome have a different profile of the HLA antigens with the presence of DR2, DQw1 and DRB3/4 allele and are negative for diabetes-related autoantibodies, which may confirm non-autoimmune β-cell destruction in this syndrome.

HLA class II alleles and the presence of circulating Epstein-Barr virus DNA in greek patients with nasopharyngeal carcinoma

International Nuclear Information System (INIS)

Karanikiotis, C.; Daniilidis, M.; Karyotis, N.; Nikolaou, A.; Bakogiannis, C.; Economopoulos, T.; Murray, S.; Papamichael, D.; Samantas, E.; Skoura, L.; Tselis, N.; Zamboglou, N.; Fountzilas, G.

2008-01-01

Background and purpose: nasopharyngeal carcinoma (NPC) represents a seldom malignancy in most developed countries. Nevertheless, NPC receives an endemic form in concrete racial entities. The aims of this study were to detect the presence of Epstein-Barr virus DNA (EBV-DNA) in peripheral blood of NPC patients, to molecularly define human leukocyte antigens (HLA) DRB1*, DQA1* and DQB1* allele frequencies, and, finally, to determine whether the genetic predisposition of an individual to NPC depends on the liability to EBV infection. Patients and methods: a total of 101 patients of Hellenic origin and nationality, with histologically proven NPC, participated in this study. EBV-DNA detection was also applied in 66 patients with EBV-related malignancies (Hodgkin's [HL] and non-Hodgkin's lymphoma [NHL]) and infectious mononucleosis (IM), as well as in 80 healthy EBV-seropositive controls. Results: 81% of the NPC patients, 77.8% with HL, 72.2% with NHL, and 66.7% with IM were EBV-DNA positive, whereas the EBV genome was detected only in 15% of the healthy controls. These differences were statistically significant in all cases. Analysis of HLA class II antigens showed decreased frequency of the DRB1*07 (p 0.003), DQA1*0103 (p = 0.002), and DQA1*0201 (p = 0.003) alleles among NPC patients. A significant association between the HLA-DR/DQ alleles and the presence of EBV-DNA in peripheral whole blood was not established. Conclusion: circulating EBV-DNA and specific HLA class II alleles may predispose to or protect from NPC. However, the results of this study suggest that the genetic predisposition of an individual to NPC is independent of the liability to EBV infection. (orig.)

HLA Class I-Mediated HIV-1 Control in Vietnamese Infected with HIV-1 Subtype A/E.

Science.gov (United States)

Chikata, Takayuki; Tran, Giang Van; Murakoshi, Hayato; Akahoshi, Tomohiro; Qi, Ying; Naranbhai, Vivek; Kuse, Nozomi; Tamura, Yoshiko; Koyanagi, Madoka; Sakai, Sachiko; Nguyen, Dung Hoai; Nguyen, Dung Thi; Nguyen, Ha Thu; Nguyen, Trung Vu; Oka, Shinichi; Martin, Maureen P; Carrington, Mary; Sakai, Keiko; Nguyen, Kinh Van; Takiguchi, Masafumi

2018-03-01

HIV-1-specific cytotoxic T cells (CTLs) play an important role in the control of HIV-1 subtype B or C infection. However, the role of CTLs in HIV-1 subtype A/E infection still remains unclear. Here we investigated the association of HLA class I alleles with clinical outcomes in treatment-naive Vietnamese infected with subtype A/E virus. We found that HLA-C*12:02 was significantly associated with lower plasma viral loads (pVL) and higher CD4 counts and that the HLA-A*29:01-B*07:05-C*15:05 haplotype was significantly associated with higher pVL and lower CD4 counts than those for individuals without these respective genotypes. Nine Pol and three Nef mutations were associated with at least one HLA allele in the HLA-A*29:01-B*07:05-C*15:05 haplotype, with a strong negative correlation between the number of HLA-associated Pol mutations and CD4 count as well as a positive correlation with pVL for individuals with these HLA alleles. The results suggest that the accumulation of mutations selected by CTLs restricted by these HLA alleles affects HIV control. IMPORTANCE Most previous studies on HLA association with disease progression after HIV-1 infection have been performed on cohorts infected with HIV-1 subtypes B and C, whereas few such population-based studies have been reported for cohorts infected with the Asian subtype A/E virus. In this study, we analyzed the association of HLA class I alleles with clinical outcomes for 536 HIV-1 subtype A/E-infected Vietnamese individuals. We found that HLA-C*12:02 is protective, while the HLA haplotype HLA-A*29:01-B*07:05-C*15:05 is deleterious. The individuals with HIV-1 mutations associated with at least one of the HLA alleles in the deleterious HLA haplotype had higher plasma viral loads and lower CD4 counts than those of individuals without the mutations, suggesting that viral adaptation and escape from HLA-mediated immune control occurred. The present study identifies a protective allele and a deleterious haplotype for HIV-1

Heme Oxygenase-1 Inhibits HLA Class I Antibody-Dependent Endothelial Cell Activation.

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Eva Zilian

Full Text Available Antibody-mediated rejection (AMR is a key limiting factor for long-term graft survival in solid organ transplantation. Human leukocyte antigen (HLA class I (HLA I antibodies (Abs play a major role in the pathogenesis of AMR via their interactions with HLA molecules on vascular endothelial cells (ECs. The antioxidant enzyme heme oxygenase (HO-1 has anti-inflammatory functions in the endothelium. As complement-independent effects of HLA I Abs can activate ECs, it was the goal of the current study to investigate the role of HO-1 on activation of human ECs by HLA I Abs. In cell cultures of various primary human macro- and microvascular ECs treatment with monoclonal pan- and allele-specific HLA I Abs up-regulated the expression of inducible proinflammatory adhesion molecules and chemokines (vascular cell adhesion molecule-1 [VCAM-1], intercellular cell adhesion molecule-1 [ICAM-1], interleukin-8 [IL-8] and monocyte chemotactic protein 1 [MCP-1]. Pharmacological induction of HO-1 with cobalt-protoporphyrin IX reduced, whereas inhibition of HO-1 with either zinc-protoporphyrin IX or siRNA-mediated knockdown increased HLA I Ab-dependent up-regulation of VCAM-1. Treatment with two carbon monoxide (CO-releasing molecules, which liberate the gaseous HO product CO, blocked HLA I Ab-dependent EC activation. Finally, in an in vitro adhesion assay exposure of ECs to HLA I Abs led to increased monocyte binding, which was counteracted by up-regulation of HO-1. In conclusion, HLA I Ab-dependent EC activation is modulated by endothelial HO-1 and targeted induction of this enzyme may be a novel therapeutic approach for the treatment of AMR in solid organ transplantation.

Associação entre HLA e leucemia em uma população brasileira de etnia mista Association between HLA and leukemia in a mixed Brazilian population

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Lúcia Aparecida Barion

2007-06-01

Full Text Available OBJETIVOS: O objetivo deste estudo foi investigar a freqüência de antígenos HLA Classe I e de alelos HLA Classe II em 164 pacientes com vários tipos de leucemias: 35 pacientes com LLA (leucemia linfóide aguda, 50 com LMA (leucemia mielóide aguda e 78 com LMC (leucemia mielóide crônica. MÉTODOS: A tipagem HLA Classe I foi realizada por microlinfocitotoxicidade e a de Classe II por PCR-SSP (polymerase chain reaction - sequence specific of primers, ambas da One Lambda (Canoga Park, CA, US. RESULTADOS: Em pacientes com LLA, as freqüências das variantes HLA-B45 e HLA-B56 foram maiores (P = 0,02; OR = 3,13; 95%IC = 0,94-10,44; P = 0,03; OR = 3,61; 95%IC = 0,47-27,64, respectivamente, quando comparadas com controles. Nos pacientes com LMA, a freqüência de HLA-B7 (P = 0,01; OR = 2,41; 95%IC = 1,25-4,67 foi maior que em controles. A presença de HLA-B45 (P= 0,01; OR = 3,29; 95%IC = 1,46-7,40 e de HLA-DRB1*04 (P = 0,002; OR = 2,17; 95%IC = 1,36-3,46 e HLA-DRB1*08 (P = 0,004; OR = 2,36; 95%IC = 1,34-4,16 foi associada ao maior risco de desenvolver LMC. CONCLUSÃO: Nossos resultados sugerem que variantes HLA conferem susceptibilidade a algumas formas de leucemia e podem prover novas ferramentas para a investigação da genética e etiologia desta doença.OBJECTIVE: The main purpose of this study was to investigate the class I HLA antigens and class II HLA allele frequencies in 164 patients with leukemia: 35 patients with ALL (acute lymphoid leukemia, 50 with AML (acute myeloid leukemia and 78 with CML (chronic myeloid leukemia. METHODS: The genotyping of class I HLA was performed by microlymphocytotoxicity and of class II by PCR-SSP (polymerase chain reaction - sequence specific of primers (One Lambda, Canoga Park, CA, USA. RESULTS: In patients with LLA, frequencies of HLA-B45 and HLA-B56 were higher (P = 0.02; OR = 3.13; 95%IC = 0.94-10.44; P = 0.03; OR = 3.61; 95%IC = 0.47-27.64, respectively, than in controls. In patients with AML, the

Three-dimensional structure discrepancy between HLA alleles for effective prediction of aGVHD severity and optimal selection of recipient-donor pairs: a proof-of-concept study.

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Han, Hongxing; Yuan, Fang; Sun, Yuying; Liu, Jinfeng; Liu, Shuguang; Luo, Yuan; Liang, Fei; Liu, Nan; Long, Juan; Zhao, Xiao; Kong, Fanhua; Xi, Yongzhi

2015-11-24

The optimal selection of recipient-donor pair and accurate prediction of acute graft-versus-host disease (aGVHD) severity are always the two most crucial works in allogeneic hematopoietic stem cell transplantation (allo-HSCT), which currently rests mostly with HLA compatibility, the most polymorphic loci in the human genome, in clinic. Thus, there is an urgent need for a rapid and reliable quantitative system for optimal recipient-donor pairs selection and accurate prediction of aGVHD severity prior to allo-HSCT. For these reasons, we have developed a new selection/prediction system for optimal recipient-donor selection and effective prediction of aGVHD severity based on HLA three-dimensional (3D) structure modeling (HLA-TDSM) discrepancy, and applied this system in a pilot randomized clinical allo-HSCT study. The 37 patient-donor pairs in the study were typed at low- and high-resolution levels for HLA-A/-B/-DRB1/-DQB1 loci. HLA-TDSM system covering the 10000 alleles in HLA class I and II consists of the revised local and coordinate root-mean-square deviation (RMSD) values for each locus. Its accuracy and reliability were confirmed using stably transfected Hmy2.CIR-HLA-B cells, TCR Vβ gene scan, and antigen-specific alloreactive cytotoxic lymphocytes. Based on the preliminary results, we theoretically defined all HLA acceptable versus unacceptable mismatched alleles. More importantly, HLA-TDSM enabled a successful retrospective verification and prospective prediction for aGVHD severity in a pilot randomized clinical allo-HSCT study of 32 recipient-donor transplant pairs. There was a strong direct correlation between single/total revised RMSD and aGVHD severity (92% in retrospective group vs 95% in prospective group). These results seem to be closely related to the 3D structure discrepancy of mismatched HLA-alleles, but not the number or loci of mismatched HLA-alleles. Our data first provide the proof-of-concept that HLA-TDSM is essential for optimal selection of

Fine mapping in the MHC region accounts for 18% additional genetic risk for celiac disease

NARCIS (Netherlands)

Gutierrez-Achury, Javier; Zhernakova, Alexandra; Pulit, Sara L.; Trynka, Gosia; Hunt, Karen A.; Romanos, Jihane; Raychaudhuri, Soumya; van Heel, David A.; Wijmenga, Cisca; de Balcker, Paul I. W.

Although dietary gluten is the trigger for celiac disease, risk is strongly influenced by genetic variation in the major histocompatibility complex (MHC) region. We fine mapped the MHC association signal to identify additional risk factors independent of the HLA-DQA1 and HLA-DQB1 alleles and

Clozapine-induced agranulocytosis is associated with rare HLA-DQB1 and HLA-B alleles

DEFF Research Database (Denmark)

Goldstein, Jacqueline I; Fredrik Jarskog, L; Hilliard, Chris

2014-01-01

Clozapine is a particularly effective antipsychotic medication but its use is curtailed by the risk of clozapine-induced agranulocytosis/granulocytopenia (CIAG), a severe adverse drug reaction occurring in up to 1% of treated individuals. Identifying genetic risk factors for CIAG could enable saf...

Additive and interaction effects at three amino acid positions in HLA-DQ and HLA-DR molecules drive type 1 diabetes risk

NARCIS (Netherlands)

Hu, Xinli; Deutsch, Aaron J; Lenz, Tobias L; Onengut-Gumuscu, Suna; Han, Buhm; Chen, Wei-Min; Howson, Joanna M M; Todd, John A; de Bakker, Paul I W; Rich, Stephen S; Raychaudhuri, Soumya

Variation in the human leukocyte antigen (HLA) genes accounts for one-half of the genetic risk in type 1 diabetes (T1D). Amino acid changes in the HLA-DR and HLA-DQ molecules mediate most of the risk, but extensive linkage disequilibrium complicates the localization of independent effects. Using

HLA class II alleles and the presence of circulating Epstein-Barr virus DNA in greek patients with nasopharyngeal carcinoma

Energy Technology Data Exchange (ETDEWEB)

Karanikiotis, C. [424 Army General Hospital, Thessaloniki (Greece); Daniilidis, M.; Karyotis, N.; Nikolaou, A. [AHEPA Hospital, Aristotle Univ. of Thessaloniki School of Medicine (Greece); Bakogiannis, C. [Hygeia Hospital, Athens (Greece); Economopoulos, T. [' Attikon' Univ. Hospital, Athens (Greece); Murray, S. [Metropolitan Hospital, Athens (Greece); Papamichael, D. [Bank of Cyprus Oncology Center, Nicosia, Cyprus (Greece); Samantas, E. [' Agii Anargiri' Cancer Hospital, Athens (Greece); Skoura, L. [' Hippokration' Hospital, Thessaloniki (Greece); Tselis, N.; Zamboglou, N. [Dept. of Radiotherapy, Offenbach Hospital (Germany); Fountzilas, G. [' Papageorgiou' Hospital, Aristotle Univ. of Thessaloniki School of Medicine (Greece)

2008-06-15

Background and purpose: nasopharyngeal carcinoma (NPC) represents a seldom malignancy in most developed countries. Nevertheless, NPC receives an endemic form in concrete racial entities. The aims of this study were to detect the presence of Epstein-Barr virus DNA (EBV-DNA) in peripheral blood of NPC patients, to molecularly define human leukocyte antigens (HLA) DRB1*, DQA1* and DQB1* allele frequencies, and, finally, to determine whether the genetic predisposition of an individual to NPC depends on the liability to EBV infection. Patients and methods: a total of 101 patients of Hellenic origin and nationality, with histologically proven NPC, participated in this study. EBV-DNA detection was also applied in 66 patients with EBV-related malignancies (Hodgkin's [HL] and non-Hodgkin's lymphoma [NHL]) and infectious mononucleosis (IM), as well as in 80 healthy EBV-seropositive controls. Results: 81% of the NPC patients, 77.8% with HL, 72.2% with NHL, and 66.7% with IM were EBV-DNA positive, whereas the EBV genome was detected only in 15% of the healthy controls. These differences were statistically significant in all cases. Analysis of HLA class II antigens showed decreased frequency of the DRB1*07 (p = 0.003), DQA1*0103 (p = 0.002), and DQA1*0201 (p = 0.003) alleles among NPC patients. A significant association between the HLA-DR/DQ alleles and the presence of EBV-DNA in peripheral whole blood was not established. Conclusion: circulating EBV-DNA and specific HLA class II alleles may predispose to or protect from NPC. However, the results of this study suggest that the genetic predisposition of an individual to NPC is independent of the liability to EBV infection. (orig.)

Epidemiología genética de la artritis reumatoide: ¿qué esperar de América Latina?

Directory of Open Access Journals (Sweden)

Angélica María Delgado-Vega

2006-12-01

Full Text Available La artritis reumatoide es una enfermedad sistémica autoinmune, crónica, que afecta principalmente las articulaciones que tienen movimiento. La enfermedad es mucho más frecuente en mujeres y su prevalencia en la población latinoamericana es cercana al 0,5%. La existencia de agregación familiar (ls= 2-17 indica su carácter hereditario. Sin embargo, la herencia de la artritis reumatoide es poligénica y no sigue un patrón mendeliano. La importancia de encontrar factores genéticos asociados con la artritis reumatoide radica en la contribución a la comprensión de los mecanismos patogénicos de la enfermedad, su posible aplicación clínica como marcadores de riesgo, diagnóstico, pronóstico, e incluso, blanco terapéutico. Mapeos genéticos llevados a cabo en diversas poblaciones en busca de loci y genes candidatos han identificado la región HLA como aquella con mayor evidencia de ligamento. Sin embargo, su fracción etiológica corresponde sólo a un tercio de la susceptibilidad genética de la enfermedad. Esto indica que genes diferentes al HLA también están implicados en la susceptibilidad a desarrollar artritis reumatoide. En Latinoamérica, los alelos HLA-RB1*0404 y TNF -308A han sido asociados de manera uniforme con la artritis reumatoide. En el presente artículo se revisan los factores genéticos de la artritis reumatoide en el marco de una aproximación lógica y ordenada establecida por la epidemiología genética, y se ofrecen algunas recomendaciones para futuros estudios en poblaciones latinoamericanas.

Genetic diversity of Cahi DRB and DQB genes of caprine MHC class ...

Indian Academy of Sciences (India)

G. R. Gowane

2018-05-31

May 31, 2018 ... of 16 of the 89 amino acid residue sites in DRB and 19 of 86 residue sites in DQB1 had more than three amino acid substitutions. Positive evolutionary ... substantially substitute the coding amino acid and ulti- ...... Health Prod.

CSF Hypocretin-1 Levels and Clinical Profiles in Narcolepsy and Idiopathic CNS Hypersomnia in Norway

Science.gov (United States)

Heier, Mona Skard; Evsiukova, Tatiana; Vilming, Steinar; Gjerstad, Michaela D.; Schrader, Harald; Gautvik, Kaare

2007-01-01

Objective: To evaluate the relationship between CSF hypocretin-1 levels and clinical profiles in narcolepsy and CNS hypersomnia in Norwegian patients. Method: CSF hypocretin-1 was measured by a sensitive radioimmunoassay in 47 patients with narcolepsy with cataplexy, 7 with narcolepsy without cataplexy, 10 with idiopathic CNS hypersomnia, and a control group. Results: Low hypocretin-1 values were found in 72% of the HLA DQB1*0602 positive patients with narcolepsy and cataplexy. Patients with low CSF hypocretin-1 levels reported more extensive muscular involvement during cataplectic attacks than patients with normal levels. Hypnagogic hallucinations and sleep paralysis occurred more frequently in patients with cataplexy than in the other patient groups, but with no correlation to hypocretin-1 levels. Conclusion: About three quarters of the HLA DQB1*0602 positive patients with narcolepsy and cataplexy had low CSF hypocretin-1 values, and appear to form a distinct clinical entity. Narcolepsy without cataplexy could not be distinguished from idiopathic CNS hypersomnia by clinical symptoms or biochemical findings. Citation: Heier MS; Evsiukova T; Vilming S; Gjerstad MD; Schrader H; Gautvik K. CSF hypocretin-1 levels and clinical profiles in narcolepsy and idiopathic CNS hypersomnia in norway. SLEEP 2007;30(8):969-973. PMID:17702265

HLA-B7-restricted islet epitopes are differentially recognized in type 1 diabetic children and adults and form weak peptide-HLA complexes

DEFF Research Database (Denmark)

Scotto, Matthieu; Afonso, Georgia; Østerbye, Thomas

2012-01-01

The cartography of β-cell epitopes targeted by CD8(+) T cells in type 1 diabetic (T1D) patients remains largely confined to the common HLA-A2 restriction. We aimed to identify β-cell epitopes restricted by the HLA-B7 (B*07:02) molecule, which is associated with mild T1D protection. Using DNA immu......1D children and adults, and are recognized by IFN-γ(+)TGF-β(+)CD8(+) T cells. These features may explain the T1D-protective effect of HLA-B7. The novel epitopes identified should find valuable applications for immune staging of HLA-B7(+) individuals....

Exceptional manifestation of polyautoimmunity in a very young girl – a case report

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Agnieszka Mroczkowska-Juchkiewicz

2017-05-01

Full Text Available Polyautoimmunity is defined as the presence of more than one autoimmune disease in a single patient. The exact pathogenic mechanisms responsible for the coexistence of distinct autoimmune diseases within an individual have not been clearly explained. We report a case of a very young girl with the extremely rare co-existence of four distinct autoimmune diseases i.e. juvenile idiopathic arthritis, type 1 diabetes mellitus, coeliac disease and autoimmune hepatitis, recognized based on validated international classification criteria. The best to our knowledge there has been no case reporting coexistence of these particular four disorders in an individual. Moreover, all these diseases occurred during first three years of life, which also cause that case unique. Molecular studies of human leukocyte antigen (HLA class II in our patient showed the presence of the HLA DRB1*01, HLA DRB1*03, HLA DQB1*02, HLA DQB1*05 molecules, which may suggest immunogenetic links between those autoimmune diseases. The presented case highlights the importance of active screening for other autoimmune diseases, if a patient with one autoimmune disease manifests with new or nonspecific symptoms.

Influence of HLA-DRB1* incompatibility on the occurrence of rejection episodes and graft survival in serologically HLA-DR-matched renal transplant combinations

NARCIS (Netherlands)

Lardy, N. M.; van der Horst, A. R.; ten Berge, I. J.; Surachno, S.; Wilmink, J. M.; de Waal, L. P.

1997-01-01

BACKGROUND: The aim of the present study was to analyze the effect of HLA-DRB1* mismatches on graft function and graft survival in 92 patients who received serologically HLA-DR split antigen-matched cadaveric renal transplants. METHODS: The polymorphic second exon of the HLA-DRB1 alleles was typed

HLA-G and IL-10 in serum in relation to HLA-G genotype and polymorphisms

DEFF Research Database (Denmark)

Hviid, Thomas Vauvert F; Rizzo, Roberta; Christiansen, Ole B

2004-01-01

-mediated cell lysis and influence cytokine expression. Recently, a possible boarder immunoregulatory function of HLA-G also in adult life has been recognized. HLA-G gene polymorphism has been linked to differences in gene expression profile of alternatively spliced HLA-G transcripts and levels of specific HLA......% of the serum samples sHLA-G1/HLA-G5 could be detected. There was no correlation between sHLA-G1/HLA-G5 and IL-10 concentrations in serum. Soluble HLA-G1/HLA-G5 was not detected in any samples homozygous for a 14-bp insertion polymorphism in exon 8 of the 3'-untranslated region (3'UTR) of the HLA-G gene ( P=0...

Analysis of ELA-DQB exon 2 polymorphism in Argentine Creole horses by PCR-RFLP and PCR-SSCP.

Science.gov (United States)

Villegas-Castagnasso, E E; Díaz, S; Giovambattista, G; Dulout, F N; Peral-García, P

2003-08-01

The second exon of equine leucocyte antigen (ELA)-DQB genes was amplified from genomic DNA of 32 Argentine Creole horses by PCR. Amplified DNA was analysed by PCR-restriction fragment length polymorphism (RFLP) and PCR-single-strand conformation polymorphism (SSCP). The PCR-RFLP analysis revealed two HaeIII patterns, four RsaI patterns, five MspI patterns and two HinfI patterns. EcoRI showed no variation in the analysed sample. Additional patterns that did not account for known exon 2 DNA sequences were observed, suggesting the existence of novel ELA-DQB alleles. PCR-SSCP analysis exhibited seven different band patterns, and the number of bands per animal ranged from four to nine. Both methods indicated that at least two DQB genes are present. The presence of more than two alleles in each animal showed that the primers employed in this work are not specific for a unique DQB locus. The improvement of this PCR-RFLP method should provide a simple and rapid technique for an accurate definition of ELA-DQB typing in horses.

Evaluation of Ion Torrent sequencing technology for rapid clinical human leucocyte antigen typing.

Science.gov (United States)

Guerra, Sandra G; Chong, Winnie; Brown, Colin J; Navarrete, Cristina V

2018-06-05

The development of techniques to define the human leucocyte antigen (HLA) region has proven to be challenging due to its high level of polymorphism. Within a clinical laboratory, a technique for high-resolution HLA typing, which is rapid and cost effective is essential. NGS has provided a rapid, high-resolution HLA typing solution, which has reduced the number of HLA ambiguities seen with other typing methods. In this study, the One Lambda NXType NGS kit was tested on the Ion Torrent PGM platform. A total of 362 registry donors from four ethnic populations (Europeans, South Asians, Africans and Chinese) were NGS HLA typed across 9-loci (HLA-A, -B, -C, -DRB1,-DRB345 -DQB1 and -DPB1). Concordance rates of 91%-98% were obtained (for HLA-A, -B, -C, -DRB1, -DQB1 and -DPB1) when compared to historical PCR-SSO HLA types, and the identification of uncommon alleles such as A*24:07:01 and C*04:82 were observed. A turnaround time of four days was achieved for typing 44 samples. However, some limitations were observed; primer locations did not allow all ambiguities to be resolved for HLA Class II where Exon I and IV amplification are needed (HLA-DRB1*04:07:01/04:92, HLA-DRB1*09:01:02/*09:21 and HLA-DRB1*12:01:01/*12:10). This study has demonstrated high-resolution typing by NGS can be achieved in an acceptable turnaround time for a clinical laboratory; however, the Ion Torrent workflow has some technical limitations that should be addressed. © 2018 John Wiley & Sons Ltd.

PERFIL GENÉTICO HLA EN FAMILIAS VENEZOLANAS: ÚTIL HERRAMIENTA BIOMÉDICA

OpenAIRE

Zoghbi, Normig; Tassinari, Paolo; Fortes, María del Pilar; Paredes, María; Gámez, Ligia; Palacios, Marina

2016-01-01

El sistema de antígenos leucocitarios Humano (Human Leukocyte Antigen, HLA) regula la respuesta inmune mediante su unión a moléculas como el receptor de células T, participando en la presentación de antígenos y el reconocimiento de lo propio en el organismo. La caracterización genética del sistema HLA en determinada población es de gran utilidad para la comprensión de mecanismos asociados a susceptibilidad o resistencia a enfermedades y en la selección de donantes/receptores en trasplantes de...

Intervening before the onset of Type 1 diabetes

DEFF Research Database (Denmark)

Reimers, Jesper Irving

2003-01-01

AIMS/HYPOTHESIS: To set up a clinical trial to establish whether nicotinamide can prevent or delay clinical onset of Type 1 diabetes. METHOD: The European Nicotinamide Diabetes Intervention Trial is a randomised, double-blind, placebo-controlled intervention trial undertaken in 18 European...... countries, Canada and the USA. Entry criteria were a first-degree family history of Type 1 diabetes, age 3-40 years, confirmed islet cell antibody (ICA) levels greater than or equal to 20 JDF units, and a non-diabetic OGTT; the study group was further characterised by intravenous glucose tolerance testing......) centile in 34%. Additional islet autoantibodies were identified in 354 trial entrants. Diabetes-associated HLA class II haplotypes were found in 84% of the younger age group and 80% of the older group. The protective haplotype HLA-DQA1*0102-DQB1*0602 was found in 10% overall. CONCLUSIONS...

Post-Traumatic Narcolepsy Associated with Thalamic/Hypothalamic Injury

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Kikyoung Yi

2015-12-01

Full Text Available The hypothalamus is an important structure that regulates sleep via hypocretin neurotransmission. Central nervous system disorders such as tumors and vascular legions involving the hypothalamus can cause secondary narcolepsy. In addition, brain trauma can contribute to post-traumatic narcolepsy despite lack of any definite brain lesion. Here, we present a case of a 37-year-old man suffering from a hypothalamus-to-thalamus hemorrhage after a traffic accident. After this trauma, he suffered from excessive daytime sleepiness and was diagnosed with post-traumatic narcolepsy by polysomnography and multiple sleep latency tests. He was positive for human leukocyte antigen (HLA-DQB1*03:01 and HLA-DQB1*06:01 antigens.

Unrelated Hematopoietic Stem Cell Donor Matching Probability and Search Algorithm

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J.-M. Tiercy

2012-01-01

Full Text Available In transplantation of hematopoietic stem cells (HSCs from unrelated donors a high HLA compatibility level decreases the risk of acute graft-versus-host disease and mortality. The diversity of the HLA system at the allelic and haplotypic level and the heterogeneity of HLA typing data of the registered donors render the search process a complex task. This paper summarizes our experience with a search algorithm that includes at the start of the search a probability estimate (high/intermediate/low to identify a HLA-A, B, C, DRB1, DQB1-compatible donor (a 10/10 match. Based on 2002–2011 searches about 30% of patients have a high, 30% an intermediate, and 40% a low probability search. Search success rate and duration are presented and discussed in light of the experience of other centers. Overall a 9-10/10 matched HSC donor can now be identified for 60–80% of patients of European descent. For high probability searches donors can be selected on the basis of DPB1-matching with an estimated success rate of >40%. For low probability searches there is no consensus on which HLA incompatibilities are more permissive, although HLA-DQB1 mismatches are generally considered as acceptable. Models for the discrimination of more detrimental mismatches based on specific amino acid residues rather than specific HLA alleles are presented.

HLA-DRB1 among patients with Vogt-Koyanagi-Harada disease in Saudi Arabia.

Science.gov (United States)

Iqniebi, Alia; Gaafar, Ameera; Sheereen, Atia; Al-Suliman, Abdullah; Mohamed, Gamal; Al-Hussein, Khaled; Tabbara, Khalid F

2009-09-12

Vogt-Koyanagi-Harada (VKH) disease is an immune-mediated disorder with autoimmune insult directed against antigens associated with melanocytes. The genetic predisposition among VKH has not been explored in Saudi Arabia. So, the purpose of this study was to investigate the association of human leukocyte antigen (HLA)-DRB1 alleles to VKH patients and to clarify the molecular genetic mechanism underlying the susceptibility or resistance to VKH disease. Genomic DNA from a total of 30 patients with VKH and 29 control subjects was extracted from peripheral blood, and HLA-DRB1 alleles were typed by polymerase chain reaction and sequence based typing (SBT). We found a statistically significant difference in the prevalence of HLA-DRB1 *0405 between the VKH patients and control subjects (p<0.05). Eleven out of thirty (36.6%) patients with VKH had positive HLA-DRB1 *0405 compared to two out of twenty-nine (6.9%) control subjects. However, there were no statistically significant differences in the HLA-DRB1 alleles *01, *0101, *0102, *0301, *04, *0403, *0404, *0701, *1001, *1101, *1112, *1301, *1302, *1303, *1501, and *1502 between the VKH patients and controls. Patients with VKH had significantly greater incidence of HLA-DRB1 *0405 when compared to age and sex-matched controls. Consequently, this finding suggests that HLA-DRB1 *0405 allele might play a role in the pathogenesis of VKH disease.

Application of High-Throughput Next-Generation Sequencing for HLA Typing on Buccal Extracted DNA: Results from over 10,000 Donor Recruitment Samples.

Science.gov (United States)

Yin, Yuxin; Lan, James H; Nguyen, David; Valenzuela, Nicole; Takemura, Ping; Bolon, Yung-Tsi; Springer, Brianna; Saito, Katsuyuki; Zheng, Ying; Hague, Tim; Pasztor, Agnes; Horvath, Gyorgy; Rigo, Krisztina; Reed, Elaine F; Zhang, Qiuheng

2016-01-01

Unambiguous HLA typing is important in hematopoietic stem cell transplantation (HSCT), HLA disease association studies, and solid organ transplantation. However, current molecular typing methods only interrogate the antigen recognition site (ARS) of HLA genes, resulting in many cis-trans ambiguities that require additional typing methods to resolve. Here we report high-resolution HLA typing of 10,063 National Marrow Donor Program (NMDP) registry donors using long-range PCR by next generation sequencing (NGS) approach on buccal swab DNA. Multiplex long-range PCR primers amplified the full-length of HLA class I genes (A, B, C) from promotor to 3' UTR. Class II genes (DRB1, DQB1) were amplified from exon 2 through part of exon 4. PCR amplicons were pooled and sheared using Covaris fragmentation. Library preparation was performed using the Illumina TruSeq Nano kit on the Beckman FX automated platform. Each sample was tagged with a unique barcode, followed by 2×250 bp paired-end sequencing on the Illumina MiSeq. HLA typing was assigned using Omixon Twin software that combines two independent computational algorithms to ensure high confidence in allele calling. Consensus sequence and typing results were reported in Histoimmunogenetics Markup Language (HML) format. All homozygous alleles were confirmed by Luminex SSO typing and exon novelties were confirmed by Sanger sequencing. Using this automated workflow, over 10,063 NMDP registry donors were successfully typed under high-resolution by NGS. Despite known challenges of nucleic acid degradation and low DNA concentration commonly associated with buccal-based specimens, 97.8% of samples were successfully amplified using long-range PCR. Among these, 98.2% were successfully reported by NGS, with an accuracy rate of 99.84% in an independent blind Quality Control audit performed by the NDMP. In this study, NGS-HLA typing identified 23 null alleles (0.023%), 92 rare alleles (0.091%) and 42 exon novelties (0.042%). Long

Application of High-Throughput Next-Generation Sequencing for HLA Typing on Buccal Extracted DNA: Results from over 10,000 Donor Recruitment Samples.

Directory of Open Access Journals (Sweden)

Yuxin Yin

Full Text Available Unambiguous HLA typing is important in hematopoietic stem cell transplantation (HSCT, HLA disease association studies, and solid organ transplantation. However, current molecular typing methods only interrogate the antigen recognition site (ARS of HLA genes, resulting in many cis-trans ambiguities that require additional typing methods to resolve. Here we report high-resolution HLA typing of 10,063 National Marrow Donor Program (NMDP registry donors using long-range PCR by next generation sequencing (NGS approach on buccal swab DNA.Multiplex long-range PCR primers amplified the full-length of HLA class I genes (A, B, C from promotor to 3' UTR. Class II genes (DRB1, DQB1 were amplified from exon 2 through part of exon 4. PCR amplicons were pooled and sheared using Covaris fragmentation. Library preparation was performed using the Illumina TruSeq Nano kit on the Beckman FX automated platform. Each sample was tagged with a unique barcode, followed by 2×250 bp paired-end sequencing on the Illumina MiSeq. HLA typing was assigned using Omixon Twin software that combines two independent computational algorithms to ensure high confidence in allele calling. Consensus sequence and typing results were reported in Histoimmunogenetics Markup Language (HML format. All homozygous alleles were confirmed by Luminex SSO typing and exon novelties were confirmed by Sanger sequencing.Using this automated workflow, over 10,063 NMDP registry donors were successfully typed under high-resolution by NGS. Despite known challenges of nucleic acid degradation and low DNA concentration commonly associated with buccal-based specimens, 97.8% of samples were successfully amplified using long-range PCR. Among these, 98.2% were successfully reported by NGS, with an accuracy rate of 99.84% in an independent blind Quality Control audit performed by the NDMP. In this study, NGS-HLA typing identified 23 null alleles (0.023%, 92 rare alleles (0.091% and 42 exon novelties (0.042%.Long

The value of some genetic factors for prediction of chronic hepatitis C antiviral treatment effectiveness

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V. M. Mitsura

2014-01-01

Full Text Available Aim: To determine the value of gene polymorphisms of interleukin-28B (IL28B, RNase L, HLA DRB1*1101 and HLADQB1*03 alleles as predictors of antiviral treatment efficacy in patients with chronic hepatitis C (CHC.Material and methods. A total of 156 in-patients with chronic hepatitis C (65.4% men, 62.4% had genotype 1 hepatitis C virus – HCV were studied. The results of treatment with interferon (IFN and ribavirin (RBV were analyzed in 74 patients. Polymerase chain reaction identified single nucleotide polymorphisms (SNP of the gene IL28B 39743165T>G (rs8099917, SNP 39738787C> T (rs12979860, RNase L gene (1385G>A, HLA DRB1*1101 and HLA-DQB1*03 alleles.Results. In patients with HCV genotype 1 mutant alleles were more common in SNP 39743165T>G (p=0.001 and 39738787C>T (p=0.0002 than in patients with other genotypes. Response to therapy IFN/RBV was higher in those with “favorable” TT variant (SNP 39743165T>G and CC (SNP 39738787C>T, in those with their combination virologic response ffect were found according to genes IL28B and RNase L SNP variants, DRB1*1101 and HLA-DQB1*03 alleles.Conclusion. Testing for SNP 39738787C>T of IL28B gene is recommended before starting therapy IFN / RBV for all patients with genotype 1 HCV as a predictor of treatment response. Testing SNP 1385G>A gene RNase L and DRB1*1101, HLA-DQB1*03 alleles has no apparent prognostic value for patients with CHC antiviral therapy.

Narcolepsy: Autoimmunity, Effector T Cell Activation Due to Infection, or T Cell Independent, Major Histocompatibility Complex Class II Induced Neuronal Loss?

Science.gov (United States)

Fontana, Adriano; Gast, Heidemarie; Reith, Walter; Recher, Mike; Birchler, Thomas; Bassetti, Claudio L.

2010-01-01

Human narcolepsy with cataplexy is a neurological disorder, which develops due to a deficiency in hypocretin producing neurons in the hypothalamus. There is a strong association with human leucocyte antigens HLA-DR2 and HLA-DQB1*0602. The disease typically starts in adolescence. Recent developments in narcolepsy research support the hypothesis of…

Lower Frequency of HLA-DRB1 Type 1 Diabetes Risk Alleles in Pediatric Patients with MODY.

Science.gov (United States)

Urrutia, Inés; Martínez, Rosa; López-Euba, Tamara; Velayos, Teresa; Martínez de LaPiscina, Idoia; Bilbao, José Ramón; Rica, Itxaso; Castaño, Luis

2017-01-01

The aim of this study was to determine the frequency of susceptible HLA-DRB1 alleles for type 1 diabetes in a cohort of pediatric patients with a confirmed genetic diagnosis of MODY. 160 families with a proband diagnosed with type 1 diabetes and 74 families with a molecular diagnosis of MODY (61 GCK-MODY and 13 HNF1A-MODY) were categorized at high definition for HLA-DRB1 locus. According to the presence or absence of the susceptible HLA-DRB1 alleles for type 1 diabetes, we considered three different HLA-DRB1 genotypes: 0 risk alleles (no DR3 no DR4); 1 risk allele (DR3 or DR4); 2 risk alleles (DR3 and/or DR4). Compared with type 1 diabetes, patients with MODY carried higher frequency of 0 risk alleles, OR 22.7 (95% CI: 10.7-48.6) and lower frequency of 1 or 2 risk alleles, OR 0.53 (95% CI: 0.29-0.96) and OR 0.06 (95% CI: 0.02-0.18), respectively. The frequency of HLA-DRB1 risk alleles for type 1 diabetes is significantly lower in patients with MODY. In children and adolescents with diabetes, the presence of 2 risk alleles (DR3 and/or DR4) reduces the probability of MODY diagnosis, whereas the lack of risk alleles increases it. Therefore, we might consider that HLA-DRB1 provides additional information for the selection of patients with high probability of monogenic diabetes.

Lower Frequency of HLA-DRB1 Type 1 Diabetes Risk Alleles in Pediatric Patients with MODY.

Directory of Open Access Journals (Sweden)

Inés Urrutia

Full Text Available The aim of this study was to determine the frequency of susceptible HLA-DRB1 alleles for type 1 diabetes in a cohort of pediatric patients with a confirmed genetic diagnosis of MODY.160 families with a proband diagnosed with type 1 diabetes and 74 families with a molecular diagnosis of MODY (61 GCK-MODY and 13 HNF1A-MODY were categorized at high definition for HLA-DRB1 locus. According to the presence or absence of the susceptible HLA-DRB1 alleles for type 1 diabetes, we considered three different HLA-DRB1 genotypes: 0 risk alleles (no DR3 no DR4; 1 risk allele (DR3 or DR4; 2 risk alleles (DR3 and/or DR4.Compared with type 1 diabetes, patients with MODY carried higher frequency of 0 risk alleles, OR 22.7 (95% CI: 10.7-48.6 and lower frequency of 1 or 2 risk alleles, OR 0.53 (95% CI: 0.29-0.96 and OR 0.06 (95% CI: 0.02-0.18, respectively.The frequency of HLA-DRB1 risk alleles for type 1 diabetes is significantly lower in patients with MODY. In children and adolescents with diabetes, the presence of 2 risk alleles (DR3 and/or DR4 reduces the probability of MODY diagnosis, whereas the lack of risk alleles increases it. Therefore, we might consider that HLA-DRB1 provides additional information for the selection of patients with high probability of monogenic diabetes.

High Frequency of Haplotype HLA-DQ7 in Celiac Disease Patients from South Italy: Retrospective Evaluation of 5,535 Subjects at Risk of Celiac Disease.

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Nadia Tinto

Full Text Available Celiac disease (CD has a strong genetic component mainly due to HLA DQ2/DQ8 encoding genes. However, a minority of CD patients are DQ2/DQ8-negative. To address this issue, we retrospectively characterized HLA haplotypes in 5,535 subjects at risk of CD (either relatives of CD patients or subjects with CD-like symptoms referred to our center during a 10-year period.We identified loci DQA1/DQB1/DRB1 by sequence-specific oligonucleotide-PCR and sequence-specific primer-PCR; anti-transglutaminase IgA/IgG and anti-endomysium IgA by ELISA and indirect immunofluorescence, respectively.We diagnosed CD in 666/5,535 individuals, 4.2% of whom were DQ2/DQ8-negative. Interestingly, DQ7 was one of the most abundant haplotypes in all CD patients and significantly more frequent in DQ2/DQ8-negative (38% than in DQ2/DQ8-positive CD patients (24% (p<0.05.Our data lend support to the concept that DQ7 represents an additive or independent CD risk haplotype with respect to DQ2/DQ8 haplotypes but this finding should be verified in other large CD populations.

Presentation of human minor histocompatibility antigens by HLA-B35 and HLA-B38 molecules

International Nuclear Information System (INIS)

Yamamoto, Junji; Kariyone, Ai; Kano, Kyoichi; Takiguchi, Masafumi; Akiyama, Nobuo

1990-01-01

Cytotoxic T lymphocyte (CTL) clones specific for human minor histocompatibility antigens (hmHAs) were produced from a patient who had been grafted with the kidneys from his mother and two HLA-identical sisters. Of eight CTL clones generated, four recognized an hmHA (hmHA-1) expressed on cells from the mother and sister 3 (second donor); two recognized another antigen (hmHA-2) on cells from the father, sister (third donor), and sister 3; and the remaining two clones recognized still another antigen (hmHA-3) on cells from the father and sister 3. Panel studies revealed that CTL recognition of hmHA-1 was restricted by HLA-B35 and that of hmHA-2 and hmHA-3 was restricted by HLA-B38. The HLA-B35 restriction of the hmHA-1 -specific CTL clones was substantiated by the fact that they killed HLA-A null/HLA-B null Hmy2CIR targets transfected with HLA-B35 but not HLA-B51, -Bw52, or -Bw53 transfected Hmy2CIR targets. These data demonstrated that the five amino acids substitutions on the α 1 domain between HLA-B35 and -Bw53, which are associated with Bw4/Bw6 epitopes, play a critical role in the relationship of hmHA-1 to HLA-B35 molecules. The fact that the hmHA-1-specific CTLs failed to kill Hmy2CIR cells expressing HLA-B35/51 chimeric molecules composed of the α 1 domain of HLA-B35 and other domains of HLA-B51 indicated that eight residues on the α 2 domain also affect the interaction of hmHA-1 and the HLA-B35 molecules

DIFFERENTIAL IMPACT OF HLA-A, HLA-B AND HLA-DR COMPATIBILITY ON THE RENAL ALLOGRAFT SURVIVAL

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V. Y. Abramov

2012-01-01

Full Text Available We studied the long-term results of 532 deceased donor kidney transplantations to investigate the impact of HLA match on the survival of renal allograft. All transplants were performed in our center in 1996–2009 and moni- tored prospectively for 1–14 years. We found, the survival of 58 kidneys grafted with 0–2 mismatch for HLA- ABDR to be significantly better (Plogrank = 0,016 than the survival of the kidneys grafted with 3–6 HLA-ABDR mismatch. The full compatibility for HLA-A (n = 75 did not influence the long-term survival (Plogrank = 0,48. The absence of HLA-DR mismatch had a beneficial effect for survival of 68 kidneys (Plogrank = 0,07. Eighteen cases with the full HLA-B compatibility between graft and recipient demonstrated excellent long-term survival (Plogrank = 0,007. HLA-B compatibility influenced significantly (P = 0,042 the survival of transplanted kidney in the Cox regression model adjusted for donor and recipient age, panel-reactive antibody level, re-transplant, and immunosuppression protocol. The data obtained support the conclusion, that HLA compatibility should be one of the criteria of deceased donor kidney allocation. 

Abstract

Indian Academy of Sciences (India)

2017-03-10

Mar 10, 2017 ... factors with low to moderate effect which have been described (Klareskog et al. 2006). The strongest ... 2014). Several studies in GWAS and meta-analyses ... All patients and healthy controls gave informed consent to .... HLA-DQB1 encoded chain of MHC-II protein and HLA-DQA2 encoded chain of MHC-II ...

Association of primary biliary cirrhosis with the allele HLA-DPB1*0301 in a German population.

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Mella, J G; Roschmann, E; Maier, K P; Volk, B A

1995-02-01

The major histocompatibility complex class II alleles at the HLA-DPB1 locus were investigated in 32 German Caucasoid patients with primary biliary cirrhosis (PBC) and compared with those from 47 normal control patients using molecular genotyping techniques. The second exon of the HLA-DPB1 gene was amplified by polymerase chain reaction (PCR) and hybridized with 25 sequence-specific oligonucleotides (SSOs) to assign the HLA-DPB1 alleles on the basis of known sequence variations, according to the protocols of the Eleventh International Histocompatibility Workshop. A strong association of PBC was found with the allele HLA-DPB1*0301. The allele HLA DPB1*0301 was present in 50% (16 of 32) of the patients with PBC compared with 13% (6 of 47) of normal controls (P corrected < .015), whereas the other HLA-DPB1 alleles showed no significant differences in both groups. The relative risk (RR) estimate for the allele HLA-DPB1*0301 was 6.8 (95% confidence limits: 2.27 to 20.57). In summary, this study clearly demonstrates an association of PBC with the HLA-DPB1*0301 allele in German Caucasoids and may add new data to the immunogenetic background of PBC, suggesting a contribution of the HLA-DPB1 gene to the genetic susceptibility of the disease.

Frequency of class I anti-HLA alloantibodies in patients infected by HIV-1

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Elza Regina Manzolli Leite

2010-02-01

Full Text Available The aim of this study was to evaluate the presence of class I anti-HLA alloantibodies in patients infected by HIV-1 and relate it with the different clinical courses of the disease. Blood samples were collected in EDTA tubes from 145 individuals. HIV-1 infection was confirmed by ELISA test. The presence of class I anti-HLA alloantibodies and HLA allele's were determined. Clinical evolution was set as fast (3 years. Class I anti-HLA alloantibodies presence was lower in healthy individuals than in those infected by HIV-1 (4.2% against 32.4%. However, an equal distribution of these alloantibodies was found among the individuals infected, independent on the clinical evolution. Thus, class I anti-HLA alloantibodies was not a determinant factor for patient worsening.O objetivo deste estudo foi avaliar a presença de aloanticorpos anti-HLA classe I em pacientes infectados pelo HIV-1 e relacioná-la aos diferentes cursos clínicos da doença. Amostras de sangue de 145 indivíduos HIV positivo foram coletadas em tubos com EDTA. A infecção pelo HIV-1 foi confirmada por teste ELISA e a presença de aloanticorpos anti-HLA classe I determinada em seguida. A evolução clínica foi definida como rápida (3 anos. A presença de aloanticorpos anti-HLA classe I foi menor em indivíduos saudáveis em relação aos infectados pelo HIV-1 (4,2% contra 32,4%. Porém, a distribuição destes aloanticorpos entre os indivíduos infectados foi igual, independente da evolução clínica. Deste modo, a presença de aloanticorpos anti-HLA classe I não é um fator determinante na piora clínica do paciente.

Cytotoxic T cell recognition of an endogenous class I HLA peptide presented by a class II HLA molecule.

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Chen, B P; Madrigal, A; Parham, P

1990-09-01

Human leukocytes were stimulated in vitro with peptides corresponding in sequence to the highly variable helix of the alpha 1 domain of various HLA-B and -C molecules. A CD4+ CD8- cytotoxic T cell line, CTL-AV, that is specific for the HLA-B7 peptide presented by HLA-DR11.1 was obtained. The HLA-DR11.2 molecule, which only differs at three residues from HLA-DR11.1, did not present the HLA-B7 peptide to CTL-AV. Peptides from the alpha 1 domain helix of other HLA-A and HLA-B molecules, but not HLA-C molecules, competed with the HLA-B7 peptide for binding to HLA-DR11.1. A cell line (WT50) that coexpresses HLA-B7 and HLA-DR11.1 was killed by CTL-AV in the absence of any added HLA-B7 peptide. The processing and presentation of HLA-B7 in these cells appears to be through the endogenous, and not the exogenous, pathway of antigen presentation. Thus, Brefeldin A inhibits presentation and chloroquine does not. Furthermore, introduction of purified HLA-B7 molecules into HLA-DR11.1+, HLA-B7- cells by cytoplasmic loading via osmotic lysis of pinosomes, but not by simple incubation, rendered them susceptible to CTL-AV killing. These results provide an example of class II major histocompatibility complex (MHC) presentation of a constitutively synthesized self protein that uses the endogenous pathway of antigen presentation. They also emphasize the capacity for presentation of MHC peptides by MHC molecules.

Polymorphism of HLA class I and class II alleles in influenza A(H1N1)pdm09 virus infected population of Assam, Northeast India.

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Dutta, Mousumi; Dutta, Prafulla; Medhi, Subhash; Borkakoty, Biswajyoti; Biswas, Dipankar

2018-05-01

Human leucocyte antigen (HLA) represents one of the most highly polymorphic systems which plays a central role in the immune response. Genetic polymorphism of HLA in influenza A(H1N1)pdm09 infected population may be an important factor in disease progression and severity that needs further probing. In this study, a total of 110 Influenza like illness patients were recruited from the population of Assam, Northeast India, from which 35 cases infected by A(H1N1)pdm09 viruses and 35 controls were typed for HLA-A, B and DRB1 locus by PCR-SSP method. A total of seven alleles of HLA-A, 16 alleles of HLA-B, and 11 alleles of HLA-DRB1 locus were identified. The most common alleles within each locus in cases were HLA-A*11 (85.71%, P = 0.046), HLA-B*35 (25%, P = 0.0001), and HLA-DRB1*15 (49.35%,  P = 0.133) as compared to the controls, HLA-A*11 (40.82%), HLA-B*35 (0.00%), and HLA-DRB1*15 (67.53%). The frequency of HLA-A*11 and HLA-B*35 were significantly higher in cases as compared to the controls. In DRB1 locus, HLA-DRB1*10 was significantly higher in cases (20.78%, P = 0.005) than that of controls (0.00%). Whereas, HLA-DRB1*15 showed a higher frequency in controls than in cases. In addition, HLA-DRB3*01 (P = 0.053), DRB4*01 (P = 1.000), and DRB5*01(P = 0.591) were also identified along with HLA-DRB1 haplotype. From this preliminary study, it is suspected that there may be a role of HLA-A*11, HLA-B*35 and HLA-DRB1*10 in conferring susceptibility to influenza A(H1N1)pdm09 infection in the study population. A larger extended study on HLA polymorphism may explain the association between HLA and influenza A(H1N1)pdm09 infection and provide insights for HLA restricted peptide based vaccines. © 2018 Wiley Periodicals, Inc.

Donor-derived HLA antibody production in patients undergoing SCT from HLA antibody-positive donors.

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Taniguchi, K; Yoshihara, S; Maruya, E; Ikegame, K; Kaida, K; Hayashi, K; Kato, R; Inoue, T; Fujioka, T; Tamaki, H; Okada, M; Onuma, T; Fujii, N; Kusunoki, Y; Soma, T; Saji, H; Ogawa, H

2012-10-01

Pre-existing donor-specific HLA antibodies in patients undergoing HLA-mismatched SCT have increasingly been recognized as a risk factor for primary graft failure. However, the clinical implications of the presence of HLA antibodies in donors remain unknown. We prospectively examined 123 related donors for the presence of HLA antibodies by using a Luminex-based single antigen assay. Of these, 1/57 (1.8%) male, 6/27 (22%) parous female and 0/39 (0%) nonparous female donors were HLA antibody-positive. Then, we determined the presence of HLA antibodies in seven patients who received SCT from antibody-positive donors. Of these, four became HLA antibody-positive after SCT. The specificities of the antibodies that emerged in the patients closely resembled those of the antibodies found in the donors, indicating their production by donor-derived plasma cells. Moreover, the kinetics of the HLA antibody levels were similar in all four patients: levels started increasing within 1 week after SCT and peaked at days 10-21, followed by a gradual decrease. These results suggest that donor-derived HLA antibody production frequently occurs in patients undergoing SCT from antibody-positive donors. Further studies are warranted for clarifying the clinical significance of donor-derived HLA antibodies, including the role of these antibodies in post transplant platelet transfusion refractoriness.

Long-term control of HIV-1 in hemophiliacs carrying slow-progressing allele HLA-B*5101.

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Kawashima, Yuka; Kuse, Nozomi; Gatanaga, Hiroyuki; Naruto, Takuya; Fujiwara, Mamoru; Dohki, Sachi; Akahoshi, Tomohiro; Maenaka, Katsumi; Goulder, Philip; Oka, Shinichi; Takiguchi, Masafumi

2010-07-01

HLA-B*51 alleles are reported to be associated with slow disease progression to AIDS, but the mechanism underlying this association is still unclear. In the present study, we analyzed the effect of HLA-B*5101 on clinical outcome for Japanese hemophiliacs who had been infected with HIV-1 before 1985 and had been recruited in 1998 for this study. HLA-B*5101(+) hemophiliacs exhibited significantly slow progression. The analysis of HLA-B*5101-restricted HIV-1-specific cytotoxic T-lymphocyte (CTL) responses to 4 HLA-B*-restricted epitopes in 10 antiretroviral-therapy (ART)-free HLA-B*5101(+) hemophiliacs showed that the frequency of Pol283-8-specific CD8(+) T cells was inversely correlated with the viral load, whereas the frequencies of CD8(+) T cells specific for 3 other epitopes were positively correlated with the viral load. The HLA-B*5101(+) hemophiliacs whose HIV-1 replication had been controlled for approximately 25 years had HIV-1 possessing the wild-type Pol283-8 sequence or the Pol283-8V mutant, which does not critically affect T-cell recognition, whereas other HLA-B*5101(+) hemophiliacs had HIV-1 with escape mutations in this epitope. The results suggest that the control of HIV-1 over approximately 25 years in HLA-B*5101-positive hemophiliacs is associated with a Pol283-8-specific CD8(+) T-cell response and that lack of control of HIV-1 is associated with the appearance of Pol283-8-specific escape mutants.

HLA-B*14

DEFF Research Database (Denmark)

Leitman, Ellen M.; Willberg, Christian B.; Tsai, Ming Han

2017-01-01

Immune control of human immunodeficiency virus type 1 (HIV) infection is typically associated with effective Gag-specific CD8+ T-cell responses. We here focus on HLA-B*14, which protects against HIV disease progression, but the immunodominant HLA-B*14-restricted anti-HIV response is Env specific...... higher functional avidity (P associated protection against HIV disease progression...... is significantly greater for HLA-B*14:02 than for HLA-B*14:01, consistent with the superior antiviral efficacy of the HLA-B*14-EL9 response. Thus, although Gag-specific CD8+ T-cell responses may usually have greater anti-HIV efficacy, factors independent of protein specificity, including functional avidity...

Screening of the target genes trans-activated by HLA-HA8 in hepatocytes

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Qi WANG

2011-06-01

Full Text Available Objective To clone and identify the target genes trans-activated by human minor histocompatibility antigen HLA-HA8 in hepatocytes with suppression subtractive hybridization(SSH and bioinfomatics technique.Methods mRNA was isolated from HepG2 cells transfected by pcDNA3.1(--HLA-HA8 and pcDNA3.1(- empty vector,and then used to synthesize the double-stranded cDNA(marked as Tester and Driver,respectively by reverse transcription.After being digested with restriction enzyme Rsa I,the tester cDNA was divided into two parts and ligated to the specific adaptor 1 and adaptor 2,respectively,and then hybridized with driver cDNA twice and underwent PCR twice.The production was subcloned into pEGM-Teasy plasmid vectors to set up the subtractive library.The library was then amplified by transfection into E.coli strain DH5α.The cDNA was sequenced and analyzed in GenBank with Blast search after PCR amplification.Results The subtractive library of genes trans-activated by HLA-HA8 was constructed successfully.The amplified library contained 101 positive clones.Colony PCR showed that all these clones contained 200-1000bp inserts.Twenty eight clones were selected randomly to analyze the sequences.The result of homologous analysis showed that altogether 16 coding sequences were gotten,of which 4 sequences were with unknown function.Conclusions The obtained sequences trans-activated by HLA-HA8 may code different proteins and play important roles in cell growth and metabolism,energy synthesis and metabolism,material transport and signal transduction.This finding will bring some new clues for the studies not only on the biological functions of HLA-HA8,but also on the HBV infection mechanism.

El complejo mayor de histocompatibilidad humano: sistema HLA

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Luis Fernando García

1989-02-01

Full Text Available

El complejo mayor de histocompatibilidad humano, o sistema HLA, está localizado en el brazo corto del cromosoma 6. Sus genes codifican tres tipos de moléculas. Los antígenos clase I (HLA-A, B, C y E están formados por una cadena pesada unida no covalentemente a la β2-microglobulina y se expresan en la superficie de la mayoría de las células nucleadas del organismo. Estos antígenos actúan como elementos de restricción en la activación de los linfocitos T CD8+. Los antígenos clase II son dímeros compuestos por cadenas α y β y su distribución tisular está limitada sólo a algunos tipos de células. Estas moléculas actúan restringiendo la presentación de antígenos a los linfocitos CD4+. Los antígenos de clase III son proteínas plasmáticas del sistema del complemento. Los diferentes loci del sistema HLA son muy polimórficos y sus productos se heredan en bloques conocidos como haplotipos. Debido a que los diferentes grupos étnicos presentan variaciones en la frecuencia de ale ios y haplotipos, el HLA ha sido muy útil en los estudios antropogenéticos. Algunos antígenos HLA están presentes en pacientes con determinadas enfermedades con una frecuencia significativamente diferente a la encontrada en la población general. Estos hallazgos han sido de gran importancia para comprender la patogénesis y los mecanismos genéticos de resistencia o susceptibilidad a dichas enfermedades. En el campo de los transplantes de órganos, la compatibilidad HLA donante-receptor correlaciona con la sobrevida del injerto. El sistema HLA también parece tener mucha importancia en los fenómenos inmunológicos que ocurren durante el

Full genotyping of a highly polymorphic human gene trait by time-resolved fluorescence resonance energy transfer.

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Edoardo Totè

Full Text Available The ability of detecting the subtle variations occurring, among different individuals, within specific DNA sequences encompassed in highly polymorphic genes discloses new applications in genomics and diagnostics. DQB1 is a gene of the HLA-II DQ locus of the Human Leukocyte Antigens (HLA system. The polymorphisms of the trait of the DQB1 gene including codons 52-57 modulate the susceptibility to a number of severe pathologies. Moreover, the donor-receiver tissue compatibility in bone marrow transplantations is routinely assessed through crossed genotyping of DQB and DQA. For the above reasons, the development of rapid, reliable and cost-effective typing technologies of DQB1 in general, and more specifically of the codons 52-57, is a relevant although challenging task. Quantitative assessment of the fluorescence resonance energy transfer (FRET efficiency between chromophores labelling the opposite ends of gene-specific oligonucleotide probes has proven to be a powerful tool to type DNA polymorphisms with single-nucleotide resolution. The FRET efficiency can be most conveniently quantified by applying a time-resolved fluorescence analysis methodology, i.e. time-correlated single-photon counting, which allows working on very diluted template specimens and in the presence of fluorescent contaminants. Here we present a full in-vitro characterization of the fluorescence responses of two probes when hybridized to oligonucleotide mixtures mimicking all the possible genotypes of the codons 52-57 trait of DQB1 (8 homozygous and 28 heterozygous. We show that each genotype can be effectively tagged by the combination of the fluorescence decay constants extrapolated from the data obtained with such probes.

Spontaneous control of HIV-1 viremia in a subject with protective HLA-B plus HLA-C alleles and HLA-C associated single nucleotide polymorphisms.

Science.gov (United States)

Moroni, Marco; Ghezzi, Silvia; Baroli, Paolo; Heltai, Silvia; De Battista, Davide; Pensieroso, Simone; Cavarelli, Mariangela; Dispinseri, Stefania; Vanni, Irene; Pastori, Claudia; Zerbi, Pietro; Tosoni, Antonella; Vicenzi, Elisa; Nebuloni, Manuela; Wong, Kim; Zhao, Hong; McHugh, Sarah; Poli, Guido; Lopalco, Lucia; Scarlatti, Gabriella; Biassoni, Roberto; Mullins, James I; Malnati, Mauro S; Alfano, Massimo

2014-12-05

Understanding the mechanisms by which some individuals are able to naturally control HIV-1 infection is an important goal of AIDS research. We here describe the case of an HIV-1(+) woman, CASE1, who has spontaneously controlled her viremia for the last 14 of her 20 years of infection. CASE1 has been clinically monitored since 1993. Detailed immunological, virological and histological analyses were performed on samples obtained between 2009 and 2011. As for other Elite Controllers, CASE1 is characterized by low to undetectable levels of plasma HIV-1 RNA, peripheral blood mononuclear cell (PBMC) associated HIV-1 DNA and reduced in vitro susceptibility of target cells to HIV-1 infection. Furthermore, a slow rate of virus evolution was demonstrated in spite the lack of assumption of any antiretroviral agent. CASE1 failed to transmit HIV-1 to either her sexual male partner or to her child born by vaginal delivery. Normal values and ratios of T and B cells were observed, along with normal histology of the intestinal mucosa. Attempts to isolate HIV-1 from her PBMC and gut-derived cells were unsuccessful, despite expression of normal cell surface levels of CD4, CCRC5 and CXCR4. CASE1 did not produce detectable anti-HIV neutralizing antibodies in her serum or genital mucosal fluid although she displayed potent T cell responses against HIV-1 Gag and Nef. CASE1 also possessed multiple genetic polymorphisms, including HLA alleles (B*14, B*57, C*06 and C*08.02) and HLA-C single nucleotide polymorphisms (SNPs, rs9264942 C/C and rs67384697 del/del), that have been previously individually associated with spontaneous control of plasma viremia, maintenance of high CD4(+) T cell counts and delayed disease progression. CASE1 has controlled her HIV-1 viremia below the limit of detection in the absence of antiretroviral therapy for more than 14 years and has not shown any sign of immunologic deterioration or disease progression. Co-expression of multiple protective HLA alleles, HLA

Correlation Between HLA-A, B and DRB1 Alleles and Severe Fever with Thrombocytopenia Syndrome.

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Shu-Jun Ding

2016-10-01

Full Text Available Severe fever with thrombocytopenia syndrome (SFTS is an emerging hemorrhagic fever caused by a tick-borne bunyavirus (SFTSV in East Asian countries. The role of human leukocyte antigen (HLA in resistance and susceptibility to SFTSV is not known. We investigated the correlation of HLA locus A, B and DRB1 alleles with the occurrence of SFTS.A total of 84 confirmed SFTS patients (patient group and 501 unrelated non-SFTS patients (healthy individuals as control group from Shandong Province were genotyped by PCR-sequence specific oligonucleotide probe (PCR-SSOP for HLA-A, B and DRB1 loci.Allele frequency was calculated and compared using χ2 test or the Fisher's exact test. A corrected P value was calculated with a bonferronis correction. Odds Ratio (OR and 95% confidence intervals (CI were calculated by Woolf's method.A total of 11 HLA-A, 23 HLA-B and 12 HLA-DRB1 alleles were identified in the patient group, whereas 15 HLA-A, 30 HLA-B and 13 HLA-DRB1 alleles were detected in the control group. The frequencies of A*30 and B*13 in the SFTS patient group were lower than that in the control group (P = 0.0341 and 0.0085, Pc = 0.5115 and 0.252. The ORs of A*30 and B*13 in the SFTS patient group were 0.54 and 0.49, respectively. The frequency of two-locus haplotype A*30-B*13 was lower in the patient group than in the control group(5.59% versus 12.27%, P = 0.037,OR = 0.41, 95%CI = 0.18-0.96 without significance(Pc>0.05. A*30-B*13-DRB1*07 and A*02-B*15-DRB1*04 had strong associations with SFTS resistance and susceptibility respectively (Pc = 0.0412 and 0.0001,OR = 0.43 and 5.07.The host HLA class I polymorphism might play an important role with the occurrence of SFTS. Negative associations were observed with HLA-A*30, HLA-B*13 and Haplotype A*30-B*13, although the associations were not statistically significant. A*30-B*13-DRB1*07 had negative correlation with the occurrence of SFTS; in contrast, haplotype A*02-B*15-DRB1*04 was positively correlated with SFTS.

HLA AND CROSS·REACTIVE ANTIGEN GROUP MATCHING FOR CADAVER KIDNEY ALLOCATION1

Science.gov (United States)

Starzl, Thomas E.; Eliasziw, Michael; Gjertson, David; Terasaki, Paul I.; Fung, John J.; Trucco, Massimo; Martell, Joan; McMichael, John; Scantlebury, Velma; Shapiro, Ron; Donner, Allan

2010-01-01

Background Allocation of cadaver kidneys by graded human leukocyte antigen (HLA) compatibility scoring arguably has had little effect on overall survival while prejudicing the transplant candidacy of African-American and other hard to match populations. Consequently, matching has been proposed of deduced amino acid residues of the individual HLA molecules shared by cross-reactive antigen groups (CREGs). We have examined the circumstances under which compatibility with either method impacted graft survival. Methods Using Cox proportional hazards regression modeling, we studied the relationship between levels of conventional HLA mismatch and other donor and recipient factors on primary cadaver kidney survival between 1981 and 1995 at the University of Pittsburgh (n=1,780) and in the United Network for Organ Sharing (UNOS) Scientific Registry during 1991–1995 (n=31,291). The results were compared with those obtained by the matching of amino acid residues that identified CREG-compatible cases with as many as four (but not five and six) HLA mismatches. Results With more than one HLA mismatch (>85% of patients in both series), most of the survival advantage of a zero mismatch was lost. None of the HLA loci were “weak.” In the UNOS (but not Pittsburgh) category of one-HLA mismatch (n=1334), a subgroup of CREG-matched recipients (35.3%) had better graft survival than the remaining 64.7%, who were CREG-mismatched. There was no advantage of a CREG match in the two- to four-HLA incompatibility tiers. Better graft survival with tacrolimus was observed in both the Pittsburgh and UNOS series. Conclusions Obligatory national sharing of cadaver kidneys is justifiable only for zero-HLA-mismatched kidneys. The potential value of CREG matching observed in the one-HLA-mismatched recipients of the UNOS (but not the Pittsburgh) experience deserves further study. PMID:9381546

HLA-DRB1 allele association with rheumatoid arthritis susceptibility and severity in Syria.

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Mourad, Jamil; Monem, Fawza

2013-02-01

Rheumatoid arthritis (RA) is a complex multifactorial chronic disease. The importance of human leukocyte antigen as a major genetic risk factor for RA was studied worldwide. Although it is widely distributed in different Syrian areas, studies of human leukocyte antigen (HLA) alleles' role are absent. The aim of our study was to determine the association of HLA-DRB1 alleles with the susceptibility and severity of RA in Syria. Eighty-six RA patients and 200 healthy controls from Syria were genotyped using polymerase chain reaction with sequence-specific primer (PCR-SSP). Anti-CCP antibodies were measured by ELISA. Rheumatoid factor (RF), C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), and disease activity score 28 (DAS-28) values were obtained from patients' medical records. DAS-28 was used to assess the clinical severity of the patients. The HLA-DRB1*01, *04, and *10 frequencies showed a strong association with the disease susceptibility (OR = 2.29, 95% CI = 1.11-4.75, P = 0.022; OR = 3.16, 95% CI = 2.0 -4.8, P < 0.0001; OR = 2.43, 95% CI = 1.07-5.51, P = 0.029 respectively), while the frequencies of HLA-DRB1*11, and *13 were significantly lower in RA patients than in controls (OR = 0.49, 95% CI = 0.3-0.8, P = 0.004; OR = 0.32, 95% CI = 0.15-0.69, P = 0.002, respectively). The other HLA-DRB1 alleles showed no significant difference. The frequency of anti-CCP antibodies was higher in shared epitope (SE) positive patients compared with SE-negative patients (OR = 5.5, 95% CI = 2-15.1, P = 0.00054). DAS-28 of RA patients didn't show significant difference between the SE negative and the SE positive groups. Our results indicate that HLA-DRB1*01, *04, and *10 alleles are related with RA, while HLA-DRB1*11 and *13 protect against RA in the Syrian population.

Identification of NY-BR-1-specific CD4(+) T cell epitopes using HLA-transgenic mice.

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Gardyan, Adriane; Osen, Wolfram; Zörnig, Inka; Podola, Lilli; Agarwal, Maria; Aulmann, Sebastian; Ruggiero, Eliana; Schmidt, Manfred; Halama, Niels; Leuchs, Barbara; von Kalle, Christof; Beckhove, Philipp; Schneeweiss, Andreas; Jäger, Dirk; Eichmüller, Stefan B

2015-06-01

Breast cancer represents the second most common cancer type worldwide and has remained the leading cause of cancer-related deaths among women. The differentiation antigen NY-BR-1 appears overexpressed in invasive mammary carcinomas compared to healthy breast tissue, thus representing a promising target antigen for T cell based tumor immunotherapy approaches. Since efficient immune attack of tumors depends on the activity of tumor antigen-specific CD4(+) effector T cells, NY-BR-1 was screened for the presence of HLA-restricted CD4(+) T cell epitopes that could be included in immunological treatment approaches. Upon NY-BR-1-specific DNA immunization of HLA-transgenic mice and functional ex vivo analysis, a panel of NY-BR-1-derived library peptides was determined that specifically stimulated IFNγ secretion among splenocytes of immunized mice. Following in silico analyses, four candidate epitopes were determined which were successfully used for peptide immunization to establish NY-BR-1-specific, HLA-DRB1*0301- or HLA-DRB1*0401-restricted CD4(+) T cell lines from splenocytes of peptide immunized HLA-transgenic mice. Notably, all four CD4(+) T cell lines recognized human HLA-DR-matched dendritic cells (DC) pulsed with lysates of NY-BR-1 expressing human tumor cells, demonstrating natural processing of these epitopes also within the human system. Finally, CD4(+) T cells specific for all four CD4(+) T cell epitopes were detectable among PBMC of breast cancer patients, showing that CD4(+) T cell responses against the new epitopes are not deleted nor inactivated by self-tolerance mechanisms. Our results present the first NY-BR-1-specific HLA-DRB1*0301- and HLA-DRB1*0401-restricted T cell epitopes that could be exploited for therapeutic intervention against breast cancer. © 2014 UICC.

HLA-A*01:03, HLA-A*24:02, HLA-B*08:01, HLA-B*27:05, HLA-B*35:01, HLA-B*44:02, and HLA-C*07:01 Monochain Transgenic/H-2 Class I Null Mice

DEFF Research Database (Denmark)

Boucherma, Rachid; Kridane-Miledi, Hédia; Bouziat, Romain

2013-01-01

We have generated a panel of transgenic mice expressing HLA-A*01:03, -A*24:02, -B*08:01, -B*27:05, -B*35:01, -B*44:02, or -C*07:01 as chimeric monochain molecules (i.e., appropriate HLA α1α2 H chain domains fused with a mouse α3 domain and covalently linked to human β2-microglobulin). Whereas...... a quantitative and qualitative restoration of the peripheral CD8(+) T cell repertoire, which exhibited a TCR diversity comparable with C57BL/6 WT mice. Potent epitope-specific, HLA-restricted, IFN-γ-producing CD8(+) T cell responses were generated against known reference T cell epitopes after either peptide...

PADI4 and the HLA-DRB1 shared epitope in juvenile idiopathic arthritis.

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Hisa, Kaori; Yanagimachi, Masakatsu D; Naruto, Takuya; Miyamae, Takako; Kikuchi, Masako; Hara, Rhoki; Imagawa, Tomoyuki; Yokota, Shumpei; Mori, Masaaki

2017-01-01

Both genetic and environmental factors are associated with susceptibility to juvenile idiopathic arthritis (JIA). Many studies have reported that both a 'shared epitope' (SE) encoded by several HLA-DRB1 alleles and the peptidyl arginine deiminase type 4 (PADI4) gene polymorphisms are associated with susceptibility to rheumatoid arthritis (RA). However, it is uncertain whether JIA and RA share the latter genetic risk factor. Therefore, here we investigated relationships between HLA-SE and PADI4 polymorphisms with clinical subtypes of JIA. JIA patients (39 oligoarthritis, 48 RF-positive polyarthritis, 19 RF-negative polyarthritis and 82 systemic) and 188 healthy controls were genotyped for HLA-DRB1 by PCR-sequence-specific oligonucleotide probe methodology. Three PADI4 gene single nucleotide polymorphisms (SNPs), rs2240340, rs2240337 and rs1748033, were genotyped using TaqMan SNP Genotyping Assays. Frequencies of the HLA-SE were higher in RF-positive polyarticular JIA than in healthy controls. RF-positive polyarticular JIA was associated with HLA-SE (OR = 5.3, 95% CI = 2.5-11.9, pc < 0.001). No associations were found between clinical subtypes of JIA and PADI4 allele frequency. Nonetheless, rs2240337 in the PADI4 gene was significantly associated with anti-cyclic citrullinated peptide antibody (ACPA)-positivity in JIA. The A allele at rs2240337 was a significant risk factor for ACPA positivity in JIA (OR = 5.6, 95% CI = 1.71-23.7 pc = 0.03). PADI4 gene polymorphism is associated with ACPA-positivity in JIA. The association of HLA-SE with RF-positive polyarticular JIA as well as RA is confirmed in Japanese. Thus, HLA-SE and PADI4 status both influence JIA clinical manifestations.

[Narcolepsy with cataplexy: an autoimmune disease?].

Science.gov (United States)

Jacob, Louis; Dauvilliers, Yves

2014-12-01

Narcolepsy type 1 (also named narcolepsy-cataplexy or hypocretin deficiency syndrome) is a rare sleep disorder characterized by excessive daytime sleepiness and cataplexy, plus frequently hypnagogic hallucinations, sleep paralysis and nocturnal sleep disturbances. Narcolepsy type 1 is an immune system-associated disease linked with the destruction of 70.000-90.000 hypocretin neurons notably involved in wakefulness. Among narcoleptic patients, 98% are positive for HLA-DQB1*06:02, a HLA class II allele, against 20-25% in general population. Individuals carrying HLA-DQB1*06:02 have an extraordinary risk to develop narcolepsy (odd ratio: 251). Other genes involved in CD4+ T cells and immune system activation as T-cell receptor α are also associated with narcolepsy. The development of the disease is linked with environmental factors such as influenza and streptococcal infections. Narcolepsy type 1 incidence also increased in Europe following the use of Pandemrix, a 2009 H1N1 AS03-adjuvanted vaccine manufactured by GlaxoSmithKline. Interestingly, such increase was not observed with Arepanrix, another vaccine developed by GSK very similar to Pandemrix. © 2014 médecine/sciences – Inserm.

Assignment of C1q-binding HLA antibodies as unacceptable HLA antigens avoids positive CDC-crossmatches prior to transplantation of deceased donor organs.

Science.gov (United States)

Juhl, David; Marget, Matthias; Hallensleben, Michael; Görg, Siegfried; Ziemann, Malte

2017-03-01

Soon, a virtual crossmatch shall replace the complement-dependent cytotoxicity (CDC) allocation crossmatch in the Eurotransplant region. To prevent positive CDC-crossmatches in the recipient centre, careful definition of unacceptable antigens is necessary. For highly sensitized patients, this is difficult by CDC alone. Assignment of all antibodies detected by sensitive assays, however, could prevent organ allocation. To assess the usefulness of the Luminex C1q-assay to prevent positive CDC-crossmatches, all CDC-crossmatches performed prior to deceased kidney transplantation in a 16-month-period were reviewed. Sera causing positive crossmatches were investigated by the C1q-assay. 31 out of 1432 crossmatches (2.2%) were positive. Sera involved in 26 positive crossmatches were available. C1q-binding donor-specific antibodies were detected in 19 sera (73.1%). The other sera were from recipients without any HLA antibodies detectable by CDC or common solid phase assays. Three patients had known Non-HLA antibodies causing positive CDC-results. Four crossmatches were only weak positive. Therefore, avoidance of donors with HLA antigens against whom C1q-binding antibodies were detected would have prevented all positive crossmatches due to HLA antibodies. Provided that all HLA specificities against which antibodies are detected by the Luminex C1q-assay are considered as unacceptable antigens, CDC-crossmatches prior to transplantation might safely be omitted in many patients. They should be maintained in highly immunized patients, however, for whom assignment of all C1q-positive antibodies as unacceptable antigens could lead to a significant delay or even prevention of transplantation. Copyright © 2017 Elsevier B.V. All rights reserved.

Long-Term Control of HIV-1 in Hemophiliacs Carrying Slow-Progressing Allele HLA-B*5101▿ †

Science.gov (United States)

Kawashima, Yuka; Kuse, Nozomi; Gatanaga, Hiroyuki; Naruto, Takuya; Fujiwara, Mamoru; Dohki, Sachi; Akahoshi, Tomohiro; Maenaka, Katsumi; Goulder, Philip; Oka, Shinichi; Takiguchi, Masafumi

2010-01-01

HLA-B*51 alleles are reported to be associated with slow disease progression to AIDS, but the mechanism underlying this association is still unclear. In the present study, we analyzed the effect of HLA-B*5101 on clinical outcome for Japanese hemophiliacs who had been infected with HIV-1 before 1985 and had been recruited in 1998 for this study. HLA-B*5101+ hemophiliacs exhibited significantly slow progression. The analysis of HLA-B*5101-restricted HIV-1-specific cytotoxic T-lymphocyte (CTL) responses to 4 HLA-B*-restricted epitopes in 10 antiretroviral-therapy (ART)-free HLA-B*5101+ hemophiliacs showed that the frequency of Pol283-8-specific CD8+ T cells was inversely correlated with the viral load, whereas the frequencies of CD8+ T cells specific for 3 other epitopes were positively correlated with the viral load. The HLA-B*5101+ hemophiliacs whose HIV-1 replication had been controlled for approximately 25 years had HIV-1 possessing the wild-type Pol283-8 sequence or the Pol283-8V mutant, which does not critically affect T-cell recognition, whereas other HLA-B*5101+ hemophiliacs had HIV-1 with escape mutations in this epitope. The results suggest that the control of HIV-1 over approximately 25 years in HLA-B*5101-positive hemophiliacs is associated with a Pol283-8-specific CD8+ T-cell response and that lack of control of HIV-1 is associated with the appearance of Pol283-8-specific escape mutants. PMID:20410273

PADI4 and the HLA-DRB1 shared epitope in juvenile idiopathic arthritis.

Directory of Open Access Journals (Sweden)

Kaori Hisa

Full Text Available Both genetic and environmental factors are associated with susceptibility to juvenile idiopathic arthritis (JIA. Many studies have reported that both a 'shared epitope' (SE encoded by several HLA-DRB1 alleles and the peptidyl arginine deiminase type 4 (PADI4 gene polymorphisms are associated with susceptibility to rheumatoid arthritis (RA. However, it is uncertain whether JIA and RA share the latter genetic risk factor. Therefore, here we investigated relationships between HLA-SE and PADI4 polymorphisms with clinical subtypes of JIA.JIA patients (39 oligoarthritis, 48 RF-positive polyarthritis, 19 RF-negative polyarthritis and 82 systemic and 188 healthy controls were genotyped for HLA-DRB1 by PCR-sequence-specific oligonucleotide probe methodology. Three PADI4 gene single nucleotide polymorphisms (SNPs, rs2240340, rs2240337 and rs1748033, were genotyped using TaqMan SNP Genotyping Assays.Frequencies of the HLA-SE were higher in RF-positive polyarticular JIA than in healthy controls. RF-positive polyarticular JIA was associated with HLA-SE (OR = 5.3, 95% CI = 2.5-11.9, pc < 0.001. No associations were found between clinical subtypes of JIA and PADI4 allele frequency. Nonetheless, rs2240337 in the PADI4 gene was significantly associated with anti-cyclic citrullinated peptide antibody (ACPA-positivity in JIA. The A allele at rs2240337 was a significant risk factor for ACPA positivity in JIA (OR = 5.6, 95% CI = 1.71-23.7 pc = 0.03.PADI4 gene polymorphism is associated with ACPA-positivity in JIA. The association of HLA-SE with RF-positive polyarticular JIA as well as RA is confirmed in Japanese. Thus, HLA-SE and PADI4 status both influence JIA clinical manifestations.

A genomic study on distribution of human leukocyte antigen (HLA-A and HLA-B alleles in Lak population of Iran

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Farhad Shahsavar

2017-03-01

Full Text Available Anthropological studies based on the highly polymorphic gene, human leukocyte antigen (HLA, provide useful information for bone marrow donor registry, forensic medicine, disease association studies, as well as infertility treatment, designing peptide vaccines against tumors, and infectious or autoimmune diseases. The aim of this study was to determine HLA-A and HLA-B allele frequencies in 100 unrelated Lak/lᴂk/individuals from Lorestan province of Iran. Finally, we compared the results with that previously described in Iranian population. Commercial HLA-Type kits from BAG (Lich, Germany company were used for determination of the HLA-A and HLA-B allele frequencies in genomic DNA, based on polymerase chain reaction with sequence specific primer (PCR-SSP assay. The differences between the populations in distribution of HLA-A and HLA-B alleles were estimated by chi-squared test with Yate's correction. The most frequent HLA-A alleles were *24 (20%, *02 (18%, *03 (12% and *11 (10%, and the most frequent HLA-B alleles were *35 (24%, *51 (16%, *18 (6% and *38 (6% in Lak population. HLA-A*66 (1%, *74(1% and HLA-B*48 (1%, *55(1% were the least observed frequencies in Lak population. Our results based on HLA-A and HLA-B allele frequencies showed that Lak population possesses the previously reported general features of Iranians but still with unique.

Estudio genético HLA en poblaciones iraníes: epidemiología, antropología y farmacogenética

OpenAIRE

Rey Medrano, Diego Federico

2015-01-01

The HLA system is the most polymorphic genetic system described in humans. It consists of several closely linked loci encoding cell surface glycoproteins whose best known function is activating immune system response through antigenic presentation. New loci and new alleles have been described since the discovery of this genetic system and the presently available DNA typing and sequencing of these new alleles have increased the variety of HLA allelism. Due to the fact that HLA gene frequencies...

Association between HLA-DQA1 gene copy number polymorphisms ...

Indian Academy of Sciences (India)

2014-04-21

Apr 21, 2014 ... 2007), type 1 diabetes (T1D) (Grayson et al. 2010), ... The aim of this study was to explore HLA-DQA1. CNVs that potentially .... McKinney C. and Merriman T. R. 2012 Meta-analysis confirms a ... Harrison A. A., Highton J. et al.

Exploring the genetic role of the HLA-DPB1 locus in Chileans with intrahepatic cholestasis of pregnancy.

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Mella, J G; Roschmann, E; Glasinovic, J C; Alvarado, A; Scrivanti, M; Volk, B A

1996-03-01

Intrahepatic cholestasis of pregnancy is a rare disease of unknown etiology, with a strikingly higher prevalence in Chile than in most other countries. Although several studies suggest that a genetic predisposition is involved in the pathogenesis, no genetic disease-marker has so far been identified. Using a recently developed HLA-genotyping technique, we performed an association study with a highly polymorphic HLA class II gene in patients with recurrent intrahepatic cholestasis of pregnancy and normal control patients. Genomic DNA was extracted from 26 unrelated patients with recurrent ICP and 30 unrelated multiparous women without a personal or family history of this disease among a Chilean population. The polymorphic second exon of the HLA-DPB1 gene was amplified by the polymerase chain reaction and hybridized with 25 sequence-specific oligonucleotide probes to assign the HLA-DPB1 alleles on the basis of known sequence variations. Out of more than 50 HLA-DPB1 alleles presently known, 13 were represented in the analyzed groups. Patients with ICP had a higher frequency of the allele DPB*0402 when compared to controls (69% vs 43%). This difference failed to reach statistical significance (x2 = 2.81, corrected p > 0.5). No significant differences were observed between the frequencies of other detected HLA-DPB1 alleles in the analyzed groups. In this study, we observed a high frequency of the allele HLA-DPB1*0402 among Chilean patients with recurrent ICP, but no association of the disease with HLA-DPB1 alleles. Therefore, HLA-DPB1 alleles do not play a major role in determining susceptibility or resistance to intrahepatic cholestasis of pregnancy.

Predictors of associated autoimmune diseases (AAID) in families with type 1 diabetes (T1D). Results from the Type 1 Diabetes Genetics Consortium (T1DGC)

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Wägner, Ana M; Santana, Ángelo; Hernández, Marta; Wiebe, Julia C; Nóvoa, Javier; Mauricio, Didac

2011-01-01

Background Type 1 diabetes (T1D) is a clinically heterogeneous disease. The presence of associated autoimmune diseases (AAID) may represent a distinct form of autoimmune diabetes, with involvement of specific mechanisms. The aim of this study was to find predictors of AAID in the Type 1 Diabetes Genetics Consortium (T1DGC) data set. Methods 3263 families with at least 2 siblings with T1D were included. Clinical information was obtained using questionnaires, anti-GAD and anti-IA-2 were measured and HLA-genotyping was performed. Siblings with T1D with and without AAID were compared and a multivariate regression analysis was performed to find predictors of AAID. T1D-associated HLA haplotypes were defined as the 4 most susceptible and protective, respectively. Results AAID was present in 14.4% of the T1D affected siblings. Age of diabetes onset, current age and time since diagnosis were higher, and there was a female predominance and more family history of AAID in the group with AAID, as well as more frequent anti-GAD and less frequent anti-IA2 positivity. Risk and protective HLA haplotype distributions were similar, though DRB1*0301-DQA1*0501-DQB1*0201 was more frequent in the group with AAID. In the multivariate analysis, female gender, age of onset, family history of AAID, time since diagnosis and anti-GAD positivity were significantly associated with AAID. Conclusions In patients with T1D, the presence of AAID is associated with female predominance, more frequent family history of AAID, later onset of T1D and more anti-GAD antibodies, despite longer duration of the disease. The predominance of certain HLA haplotypes suggests that specific mechanisms of disease may be involved. PMID:21744463

Therapeutic preparations of IVIg contain naturally occurring anti-HLA-E antibodies that react with HLA-Ia (HLA-A/-B/-Cw) alleles.

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Ravindranath, Mepur H; Terasaki, Paul I; Pham, Tho; Jucaud, Vadim; Kawakita, Satoru

2013-03-14

The US Food and Drug Administration approved intravenous immunoglobulin (IVIg), extracted from the plasma of thousands of blood donors, for removing HLA antibodies (Abs) in highly sensitized patients awaiting organ transplants. Since the blood of healthy individuals has HLA Abs, we tested different IVIg preparations for reactivity to HLA single antigen Luminex beads. All preparations showed high levels of HLA-Ia and -Ib reactivity. Since normal nonalloimmunized males have natural antibodies to the heavy chains (HCs) of HLA antigens, the preparations were then tested against iBeads coated only with intact HLA antigens. All IVIg preparations varied in level of antibody reactivity to intact HLA antigens. We raised monoclonal Abs against HLA-E that mimicked IVIg's HLA-Ia and HLA-Ib reactivity but reacted only to HLA-I HCs. Inhibition experiments with synthetic peptides showed that HLA-E shares epitopes with HLA-Ia alleles. Importantly, depleting anti-HLA-E Abs from IVIg totally eliminated the HLA-Ia reactivity of IVIg. Since anti-HLA-E mAbs react with HLA-Ia, they might be useful in suppressing HLA antibody production, similar to the way anti-RhD Abs suppress production. At the same time, anti-HLA-E mAb, which reacts only to HLA-I HCs, is unlikely to produce transfusion-related acute lung injury, in contrast to antibodies reacting to intact-HLA.

Distribution of HLA-A, -B, and -C Alleles and HLA/KIR Combinations in Han Population in China

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Yunsong Shen

2014-01-01

Full Text Available We investigated polymorphisms of the human leukocyte antigen (HLA class I (A, B, and C loci of a Han population (n, 239 from the Yunnan province, Southwest China, using high-resolution polymerase chain reaction-Luminex (PCR-Luminex typing. We combined the HLA data from this study with the KIR genotypes from a previous study of this Han population to analyze the combination of KIR/HLA ligands. A total of 27 HLA-A, 54 HLA-B, and 31 HLA-C alleles were found in this population. The frequencies of A*11:01, A*24:02, B*40:01, B*46:01, C*01:02, C*03:04, and C*07:02 were all > 10%. The following haplotypes were common, with frequencies > 5%: 1 A-B (A*02:07-B*46:01, 2 A-C (A*02:07-C*01:02, and A*11:01-C*07:02, 4 C-B (B*13:01-C*03:04, B*40:01-C*07:02, B*46:01-C*01:02 and B*58:01-C*03:02, and 1 A-C-B (A*02:07-C*01:02-B*46:01. Analysis of KIR3D and their ligands HLA-A3/A11 and HLA-Bw4 showed that the frequencies of 3DL2+-A3/A11+ and 3DL2+-A3/A11− were 0.527 and 0.473, and the frequencies of 3DL1+-Bw4+, 3DL1+-Bw4−, 3DL1−-Bw4+, and 3DL1−-Bw4− were 0.552, 0.397, 0.038, and 0.013, respectively. The results of KIR/HLA-C combination analysis showed that all individuals had at least one inhibitory or activating KIR/HLA-C pair, and one KIR/HLA-C pair was the most frequent (157/239, followed by two pairs (46/239, three pairs (33/239, and no pairs (3/239. Comparison of KIR gene and HLA gene and their pair frequency between Yunnan Han and the isolated Han (FYDH who also lived in Yunnan province showed no significant difference (P>0.05 in KIR frequencies, but significant differences (P0.05 between the two populations for KIR/HLA pairs.

Aspectos genéticos da SAOS Genetic aspects of obstructive sleep apnea syndrome

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Adriane C. Mesquita Petruco

2010-06-01

Full Text Available A fisiopatologia da SAOS é resultante da interação entre fatores genéticos e ambientais. Os mais importantes fatores de risco são obesidade e idade. Outros fatores relevantes são anormalidades craniofaciais, hipotireoidismo, menopausa e uso de álcool e de sedativos. A hereditariedade tem sido relacionada a SAOS pela a associação de SAOS a níveis de HLA, obesidade, síndromes genéticas, etnias, sonolência excessiva, alteração do controle ventilatório, expressão de mediadores inflamatórios, entre outros. Este capítulo aborda a variabilidade genética e fenotípica da doença, demonstrando sua relevância no entendimento da fisiopatologia e na avaliação clínica de SAOS.The physiopathology of obstructive sleep apnea syndrome (OSAS results from the interaction between genetic and environmental factors. The principal risk factors are obesity and age. Other relevant risk factors are craniofacial abnormalities, hypothyroidism and menopause, as well as the use of alcohol and sedatives. By virtue of its association with factors such as HLA levels, obesity, genetic syndromes, ethnicity, excessive sleepiness, alterations in ventilatory control and expression of inflammatory mediators, OSAS has been related to heritability. This chapter addresses the genetic and phenotypic variability of the disease, showing its relevance in the understanding of the physiopathology and clinical evaluation of OSAS.

Association of HLA-A and HLA-B Alleles with Lamotrigine-Induced Cutaneous Adverse Drug Reactions in the Thai Population

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Napatrupron Koomdee

2017-11-01

Full Text Available Background: Lamotrigine (LTG is commonly used for treatment of epilepsy and bipolar disorder. It is one of the common cause of cutaneous adverse drug reactions (CADR. Clinical symptoms of LTG-induced CADR range from maculopapular exanthema (MPE to severe cutaneous adverse reactions (SCAR. This study aimed to determine the association of the LTG-induced CADR with human leukocyte antigen (HLA alleles in Thai patients.Methods: Fifteen patients with LTG-induced CADR [10 MPE; 4 Stevens–Johnson syndrome; and 1 drug reaction with eosinophilia and systemic symptoms] and 50 LTG-tolerant controls were included in the study. HLA-A and HLA-B genotyping was performed using polymerase chain reaction-sequence-specific oligonucleotides probes.Results: The proportion of HLA-A∗02:07 and HLA-B∗15:02 allele carriers were significantly higher in the LTG-induced CADR group than in the tolerant controls [odds ratio (OR: 7.83; 95% confidence interval (CI: 1.60–38.25; P = 0.013, and OR: 4.89; 95% CI: 1.28–18.67; P = 0.014]. In addition, subjects with HLA-A∗33:03, HLA-B∗15:02, and HLA-B∗44:03 were significantly higher in the LTG-induced MPE group than in the tolerant controls (OR: 8.27; 95% CI: 1.83–37.41; P = 0.005, OR: 7.33; 95% CI: 1.63–33.02; P = 0.005; and OR: 10.29; 95% CI: 1.45–72.81; P = 0.029. In contrast to the LTG-induced MPE group, there were no significant differences between HLA alleles and LTG-induced SCAR group.Conclusion:HLA-A∗02:07 and HLA-B∗15:02 were associated with LTG-induced CADR in Thai patients. We also identified an association between HLA-A∗33:03, HLA-B∗15:02, and HLA-B∗44:03 and LTG-induced MPE in this population. These results suggest that these alleles could be useful screening markers for preventing CADR before LTG treatment in Thai patients, but further replication studies with larger sample sizes are needed.

The major genetic determinants of HIV-1 control affect HLA class I peptide presentation.

Science.gov (United States)

Pereyra, Florencia; Jia, Xiaoming; McLaren, Paul J; Telenti, Amalio; de Bakker, Paul I W; Walker, Bruce D; Ripke, Stephan; Brumme, Chanson J; Pulit, Sara L; Carrington, Mary; Kadie, Carl M; Carlson, Jonathan M; Heckerman, David; Graham, Robert R; Plenge, Robert M; Deeks, Steven G; Gianniny, Lauren; Crawford, Gabriel; Sullivan, Jordan; Gonzalez, Elena; Davies, Leela; Camargo, Amy; Moore, Jamie M; Beattie, Nicole; Gupta, Supriya; Crenshaw, Andrew; Burtt, Noël P; Guiducci, Candace; Gupta, Namrata; Gao, Xiaojiang; Qi, Ying; Yuki, Yuko; Piechocka-Trocha, Alicja; Cutrell, Emily; Rosenberg, Rachel; Moss, Kristin L; Lemay, Paul; O'Leary, Jessica; Schaefer, Todd; Verma, Pranshu; Toth, Ildiko; Block, Brian; Baker, Brett; Rothchild, Alissa; Lian, Jeffrey; Proudfoot, Jacqueline; Alvino, Donna Marie L; Vine, Seanna; Addo, Marylyn M; Allen, Todd M; Altfeld, Marcus; Henn, Matthew R; Le Gall, Sylvie; Streeck, Hendrik; Haas, David W; Kuritzkes, Daniel R; Robbins, Gregory K; Shafer, Robert W; Gulick, Roy M; Shikuma, Cecilia M; Haubrich, Richard; Riddler, Sharon; Sax, Paul E; Daar, Eric S; Ribaudo, Heather J; Agan, Brian; Agarwal, Shanu; Ahern, Richard L; Allen, Brady L; Altidor, Sherly; Altschuler, Eric L; Ambardar, Sujata; Anastos, Kathryn; Anderson, Ben; Anderson, Val; Andrady, Ushan; Antoniskis, Diana; Bangsberg, David; Barbaro, Daniel; Barrie, William; Bartczak, J; Barton, Simon; Basden, Patricia; Basgoz, Nesli; Bazner, Suzane; Bellos, Nicholaos C; Benson, Anne M; Berger, Judith; Bernard, Nicole F; Bernard, Annette M; Birch, Christopher; Bodner, Stanley J; Bolan, Robert K; Boudreaux, Emilie T; Bradley, Meg; Braun, James F; Brndjar, Jon E; Brown, Stephen J; Brown, Katherine; Brown, Sheldon T; Burack, Jedidiah; Bush, Larry M; Cafaro, Virginia; Campbell, Omobolaji; Campbell, John; Carlson, Robert H; Carmichael, J Kevin; Casey, Kathleen K; Cavacuiti, Chris; Celestin, Gregory; Chambers, Steven T; Chez, Nancy; Chirch, Lisa M; Cimoch, Paul J; Cohen, Daniel; Cohn, Lillian E; Conway, Brian; Cooper, David A; Cornelson, Brian; Cox, David T; Cristofano, Michael V; Cuchural, George; Czartoski, Julie L; Dahman, Joseph M; Daly, Jennifer S; Davis, Benjamin T; Davis, Kristine; Davod, Sheila M; DeJesus, Edwin; Dietz, Craig A; Dunham, Eleanor; Dunn, Michael E; Ellerin, Todd B; Eron, Joseph J; Fangman, John J W; Farel, Claire E; Ferlazzo, Helen; Fidler, Sarah; Fleenor-Ford, Anita; Frankel, Renee; Freedberg, Kenneth A; French, Neel K; Fuchs, Jonathan D; Fuller, Jon D; Gaberman, Jonna; Gallant, Joel E; Gandhi, Rajesh T; Garcia, Efrain; Garmon, Donald; Gathe, Joseph C; Gaultier, Cyril R; Gebre, Wondwoosen; Gilman, Frank D; Gilson, Ian; Goepfert, Paul A; Gottlieb, Michael S; Goulston, Claudia; Groger, Richard K; Gurley, T Douglas; Haber, Stuart; Hardwicke, Robin; Hardy, W David; Harrigan, P Richard; Hawkins, Trevor N; Heath, Sonya; Hecht, Frederick M; Henry, W Keith; Hladek, Melissa; Hoffman, Robert P; Horton, James M; Hsu, Ricky K; Huhn, Gregory D; Hunt, Peter; Hupert, Mark J; Illeman, Mark L; Jaeger, Hans; Jellinger, Robert M; John, Mina; Johnson, Jennifer A; Johnson, Kristin L; Johnson, Heather; Johnson, Kay; Joly, Jennifer; Jordan, Wilbert C; Kauffman, Carol A; Khanlou, Homayoon; Killian, Robert K; Kim, Arthur Y; Kim, David D; Kinder, Clifford A; Kirchner, Jeffrey T; Kogelman, Laura; Kojic, Erna Milunka; Korthuis, P Todd; Kurisu, Wayne; Kwon, Douglas S; LaMar, Melissa; Lampiris, Harry; Lanzafame, Massimiliano; Lederman, Michael M; Lee, David M; Lee, Jean M L; Lee, Marah J; Lee, Edward T Y; Lemoine, Janice; Levy, Jay A; Llibre, Josep M; Liguori, Michael A; Little, Susan J; Liu, Anne Y; Lopez, Alvaro J; Loutfy, Mono R; Loy, Dawn; Mohammed, Debbie Y; Man, Alan; Mansour, Michael K; Marconi, Vincent C; Markowitz, Martin; Marques, Rui; Martin, Jeffrey N; Martin, Harold L; Mayer, Kenneth Hugh; McElrath, M Juliana; McGhee, Theresa A; McGovern, Barbara H; McGowan, Katherine; McIntyre, Dawn; Mcleod, Gavin X; Menezes, Prema; Mesa, Greg; Metroka, Craig E; Meyer-Olson, Dirk; Miller, Andy O; Montgomery, Kate; Mounzer, Karam C; Nagami, Ellen H; Nagin, Iris; Nahass, Ronald G; Nelson, Margret O; Nielsen, Craig; Norene, David L; O'Connor, David H; Ojikutu, Bisola O; Okulicz, Jason; Oladehin, Olakunle O; Oldfield, Edward C; Olender, Susan A; Ostrowski, Mario; Owen, William F; Pae, Eunice; Parsonnet, Jeffrey; Pavlatos, Andrew M; Perlmutter, Aaron M; Pierce, Michael N; Pincus, Jonathan M; Pisani, Leandro; Price, Lawrence Jay; Proia, Laurie; Prokesch, Richard C; Pujet, Heather Calderon; Ramgopal, Moti; Rathod, Almas; Rausch, Michael; Ravishankar, J; Rhame, Frank S; Richards, Constance Shamuyarira; Richman, Douglas D; Rodes, Berta; Rodriguez, Milagros; Rose, Richard C; Rosenberg, Eric S; Rosenthal, Daniel; Ross, Polly E; Rubin, David S; Rumbaugh, Elease; Saenz, Luis; Salvaggio, Michelle R; Sanchez, William C; Sanjana, Veeraf M; Santiago, Steven; Schmidt, Wolfgang; Schuitemaker, Hanneke; Sestak, Philip M; Shalit, Peter; Shay, William; Shirvani, Vivian N; Silebi, Vanessa I; Sizemore, James M; Skolnik, Paul R; Sokol-Anderson, Marcia; Sosman, James M; Stabile, Paul; Stapleton, Jack T; Starrett, Sheree; Stein, Francine; Stellbrink, Hans-Jurgen; Sterman, F Lisa; Stone, Valerie E; Stone, David R; Tambussi, Giuseppe; Taplitz, Randy A; Tedaldi, Ellen M; Telenti, Amalio; Theisen, William; Torres, Richard; Tosiello, Lorraine; Tremblay, Cecile; Tribble, Marc A; Trinh, Phuong D; Tsao, Alice; Ueda, Peggy; Vaccaro, Anthony; Valadas, Emilia; Vanig, Thanes J; Vecino, Isabel; Vega, Vilma M; Veikley, Wenoah; Wade, Barbara H; Walworth, Charles; Wanidworanun, Chingchai; Ward, Douglas J; Warner, Daniel A; Weber, Robert D; Webster, Duncan; Weis, Steve; Wheeler, David A; White, David J; Wilkins, Ed; Winston, Alan; Wlodaver, Clifford G; van't Wout, Angelique; Wright, David P; Yang, Otto O; Yurdin, David L; Zabukovic, Brandon W; Zachary, Kimon C; Zeeman, Beth; Zhao, Meng

2010-12-10

Infectious and inflammatory diseases have repeatedly shown strong genetic associations within the major histocompatibility complex (MHC); however, the basis for these associations remains elusive. To define host genetic effects on the outcome of a chronic viral infection, we performed genome-wide association analysis in a multiethnic cohort of HIV-1 controllers and progressors, and we analyzed the effects of individual amino acids within the classical human leukocyte antigen (HLA) proteins. We identified >300 genome-wide significant single-nucleotide polymorphisms (SNPs) within the MHC and none elsewhere. Specific amino acids in the HLA-B peptide binding groove, as well as an independent HLA-C effect, explain the SNP associations and reconcile both protective and risk HLA alleles. These results implicate the nature of the HLA-viral peptide interaction as the major factor modulating durable control of HIV infection.

Microsatellite and HLA class II oligonucleotide typing in a population of Yanomami Indians.

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Roewer, L; Nagy, M; Schmidt, P; Epplen, J T; Herzog-Schröder, G

1993-01-01

We have used three different microsatellites (on chromosome 12 and Y) together with HLA class II oligonucleotide typing (DQA and DQB) to analyze families of Yanomami indians settling in villages in Southern Venezuela. There exist complex networks of biological relationship between villages as a result of wife exchange, village fissioning and changing patterns of alliances associated with inter-village warfare. Social status in this society is largely determined by the kinship system. Polygyny is common, especially among headmen, with additional wives, frequently being chosen among the sisters of the first wife. Our preliminary results mainly obtained from inhabitants of the village HAP show the expected allele distribution in populations with a high degree of consanguinity: (i) deficiency of observed heterozygotes at the autosomal loci and (ii) almost all men carry the same Y chromosomal allele. Nevertheless in the Yanomami village two thirds of the described autosomal microsatellite alleles were identified. Several paternities were clarified.

Identification of novel genetic markers associated with clinical phenotypes of systemic sclerosis through a genome-wide association strategy.

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Olga Gorlova

2011-07-01

Full Text Available The aim of this study was to determine, through a genome-wide association study (GWAS, the genetic components contributing to different clinical sub-phenotypes of systemic sclerosis (SSc. We considered limited (lcSSc and diffuse (dcSSc cutaneous involvement, and the relationships with presence of the SSc-specific auto-antibodies, anti-centromere (ACA, and anti-topoisomerase I (ATA. Four GWAS cohorts, comprising 2,296 SSc patients and 5,171 healthy controls, were meta-analyzed looking for associations in the selected subgroups. Eighteen polymorphisms were further tested in nine independent cohorts comprising an additional 3,175 SSc patients and 4,971 controls. Conditional analysis for associated SNPs in the HLA region was performed to explore their independent association in antibody subgroups. Overall analysis showed that non-HLA polymorphism rs11642873 in IRF8 gene to be associated at GWAS level with lcSSc (P = 2.32×10(-12, OR = 0.75. Also, rs12540874 in GRB10 gene (P = 1.27 × 10(-6, OR = 1.15 and rs11047102 in SOX5 gene (P = 1.39×10(-7, OR = 1.36 showed a suggestive association with lcSSc and ACA subgroups respectively. In the HLA region, we observed highly associated allelic combinations in the HLA-DQB1 locus with ACA (P = 1.79×10(-61, OR = 2.48, in the HLA-DPA1/B1 loci with ATA (P = 4.57×10(-76, OR = 8.84, and in NOTCH4 with ACA P = 8.84×10(-21, OR = 0.55 and ATA (P = 1.14×10(-8, OR = 0.54. We have identified three new non-HLA genes (IRF8, GRB10, and SOX5 associated with SSc clinical and auto-antibody subgroups. Within the HLA region, HLA-DQB1, HLA-DPA1/B1, and NOTCH4 associations with SSc are likely confined to specific auto-antibodies. These data emphasize the differential genetic components of subphenotypes of SSc.

Dynamic range of Nef-mediated evasion of HLA class II-restricted immune responses in early HIV-1 infection.

Science.gov (United States)

Mahiti, Macdonald; Brumme, Zabrina L; Jessen, Heiko; Brockman, Mark A; Ueno, Takamasa

2015-07-31

HLA class II-restricted CD4(+) T lymphocytes play an important role in controlling HIV-1 replication, especially in the acute/early infection stage. But, HIV-1 Nef counteracts this immune response by down-regulating HLA-DR and up-regulating the invariant chain associated with immature HLA-II (Ii). Although functional heterogeneity of various Nef activities, including down-regulation of HLA class I (HLA-I), is well documented, our understanding of Nef-mediated evasion of HLA-II-restricted immune responses during acute/early infection remains limited. Here, we examined the ability of Nef clones from 47 subjects with acute/early progressive infection and 46 subjects with chronic progressive infection to up-regulate Ii and down-regulate HLA-DR and HLA-I from the surface of HIV-infected cells. HLA-I down-regulation function was preserved among acute/early Nef clones, whereas both HLA-DR down-regulation and Ii up-regulation functions displayed relatively broad dynamic ranges. Nef's ability to down-regulate HLA-DR and up-regulate Ii correlated positively at this stage, suggesting they are functionally linked in vivo. Acute/early Nef clones also exhibited higher HLA-DR down-regulation and lower Ii up-regulation functions compared to chronic Nef clones. Taken together, our results support enhanced Nef-mediated HLA class II immune evasion activities in acute/early compared to chronic infection, highlighting the potential importance of these functions following transmission. Copyright © 2015 Elsevier Inc. All rights reserved.

IFNA-AS1 regulates CD4+ T cell activation in myasthenia gravis though HLA-DRB1.

Science.gov (United States)

Luo, Mengchuan; Liu, Xiaofang; Meng, Huanyu; Xu, Liqun; Li, Yi; Li, Zhibin; Liu, Chang; Luo, Yue-Bei; Hu, Bo; Xue, Yuanyuan; Liu, Yu; Luo, Zhaohui; Yang, Huan

2017-10-01

Abnormal CD4 + T cell activation is known to play roles in the pathogenesis of myasthenia gravis (MG). However, little is known about the mechanisms underlying the roles of lncRNAs in regulating CD4 + T cell. In this study, we discovered that the lncRNA IFNG-AS1 is abnormally expressed in MG patients associated with quantitative myasthenia gravis (QMG) and the positive anti-AchR Ab levels patients. IFNG-AS1 influenced Th1/Treg cell proliferation and regulated the expression levels of their transcription factors in an experimental autoimmune myasthenia gravis (EAMG)model. IFNG-AS1 could reduce the expression of HLA-DRB and HLA-DOB and they had a negative correlation in MG. Furthermore IFNG-AS1 influenced the expression levels of CD40L and CD4 + T cells activation in MG patient partly depend on effecting the HLA-DRB1 expression. It suggests that IFNG-AS1 may be involved in CD4 + T cell-mediated immune responses in MG. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

HLA-DQA1 typing in Danes by two polymerase chain reaction (PCR) based methods

DEFF Research Database (Denmark)

Cowland, J B; Madsen, H O; Morling, N

1995-01-01

(ASA) method, which together recognise eight alleles. In 146 unrelated Danish individuals, the HLA-DQA1 alleles were in Hardy-Weinberg equilibrium. For identity testing, the power of discrimination (PD) of HLA-DQA1 was 0.932 with the RDB method and 0.942 with the PCR-RFLP/ASA method. For paternity...

DNA typing for HLA-DPB1*02 and -DPB1*04 in multiple sclerosis and juvenile rheumatoid arthritis

DEFF Research Database (Denmark)

Fugger, L; Ryder, L P; Morling, N

1990-01-01

DP gene typing using in vitro DNA amplification combined with sequence-specific oligonucleotide probes (SSOP) has recently been reported. The amplification step may be specific for the HLA-DPB locus, or it may be specific for one or a group of HLA-DPB alleles, thus increasing the discriminatory...... power of the system. We report the combined use of group-specific DNA in vitro amplification followed by SSOP in typing for DPB1*02 and DPB1*04 variants. The method was used to type for these variants in 96 randomly selected, healthy Danes, in 37 patients with pauciarticular juvenile rheumatoid...... based on the cellularly defined HLA-DP types of the patients and the frequencies of the DPB1*02 and DPB1*04 variants among healthy Danes....

Human leukocyte antigen class I and II alleles and cervical adenocarcinoma: a pooled analysis of two epidemiologic studies

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Mahboobeh eSafaeian

2014-06-01

Full Text Available Associations between human leukocyte antigens (HLA alleles and cervical cancer are largely representative of squamous cell carcinoma (SCC, the major histologic subtype. We evaluated the association between HLA class I (A, B, and C and class II (DRB1 and DQB1 loci and risk of cervical adenocarcinoma (ADC, a less common but aggressive histologic subtype.We pooled data from the Eastern and Western US cervical cancer studies, and evaluated the association between individual alleles and allele combinations and ADC (n=630 ADC; n=775 controls. Risk estimates were calculated for 11 a priori (based on known associations with cervical cancer regardless of histologic type and 38 non a priori common alleles, as odds ratios (OR and 95% confidence intervals (CI, adjusted for age and study. In exploratory analysis, we compared the risk associations between subgroups with HPV16 or HPV18 DNA in ADC tumor tissues in the Western US study cases and controls. Three of the a priori alleles were significantly associated with decreased risk of ADC (DRB1*13:01 (OR=0.61; 95%CI:0.41-0.93, DRB1*13:02 (OR=0.49; 95%CI:0.31-0.77, and DQB1*06:03 (OR=0.64; 95%CI:0.42-0.95; one was associated with increased risk (B*07:02(OR=1.39; 95%CI:1.07-1.79. Among alleles not previously reported, DQB1*06:04 (OR=0.46; 95%CI: 0.27-0.78 was associated with decreased risk of ADC and C*07:02 (OR=1.41; 95%CI:1.09-1.81 was associated with increased risk. We did not observe a difference by histologic subtype. ADC was most strongly associated with increased risk with B*07:02/C*07:02 alleles (OR=1.33; 95%CI:1.01-1.76 and decreased risk with DRB1*13:02/DQB1*06:04 (OR=0.41; 95%CI:0.21-0.80. Results suggest that HLA allele associations with cervical ADC are similar to those for cervical SCC. An intriguing finding was the difference in risk associated with several alleles restricted to HPV16 or HPV18 related tumors, consistent with the hypothesis that HLA recognition is HPV type specific.

HLA-DQ Mismatching and Kidney Transplant Outcomes.

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Leeaphorn, Napat; Pena, Jeremy Ryan A; Thamcharoen, Natanong; Khankin, Eliyahu V; Pavlakis, Martha; Cardarelli, Francesca

2018-05-07

Recent evidence suggests that HLA epitope-mismatching at HLA-DQ loci is associated with the development of anti-DQ donor-specific antibodies and adverse graft outcomes. However, the clinical significance of broad antigen HLA-DQ mismatching for graft outcomes is not well examined. Using the United Network Organ Sharing/the Organ Procurement and Transplantation Network (UNOS/OPTN) data, patients with primary kidney transplants performed between 2005 and 2014 were included. Patients were classified as having either zero HLA-DQ mismatches, or one or two HLA-DQ mismatches. Primary outcomes were death-censored graft survival and incidence of acute rejection. A total of 93,782 patients were included. Of these, 22,730 (24%) and 71,052 (76%) received zero and one or two HLA-DQ mismatched kidneys, respectively. After adjusting for variables including HLA-ABDR, HLA-DQ mismatching was associated with a higher risk of graft loss in living kidney donor recipients with an adjusted hazard ratio (HR) of 1.18 (95% confidence interval [95% CI], 1.07 to 1.30; P HLA-DQ mismatching was associated with a higher risk of graft loss in deceased kidney donor recipients with cold ischemic time ≤17 hours (HR, 1.12; 95% CI, 1.02 to 1.27; P =0.002), but not in deceased kidney donor recipients with cold ischemic time >17 hours (HR, 0.97; 95% CI, 0.88 to 1.06; P =0.49) ( P value for interaction HLA-DQ mismatched kidneys had a higher incidence of acute rejection at 1 year, with adjusted odds ratios of 1.13 (95% CI, 1.03 to 1.23; P transplant recipients. Specific donor-DQ mismatches seemed to be associated with the risk of acute rejection and graft failure, whereas others did not. HLA-DQ mismatching is associated with lower graft survival independent of HLA-ABDR in living donor kidney transplants and deceased donor kidney transplants with cold ischemia time ≤17 hours, and a higher 1-year risk of acute rejection in living and deceased donor kidney transplants. Copyright © 2018 by the American

Human leukocyte antigen (HLA) polymorphism and type 1 diabetes ...

African Journals Online (AJOL)

Insulin-dependent diabetes mellitus or type 1 diabetes is an autoimmune multifactorial disease which has a great socio-economic impact. In Morocco, less is known about the contribution of Human leukocyte antigen (HLA) alleles to type 1 diabetes susceptibility. Our study focused on evaluating the distribution of class II ...

Increased β-haemolytic group A streptococcal M6 serotype and streptodornase B-specific cellular immune responses in Swedish narcolepsy cases.

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Ambati, A; Poiret, T; Svahn, B-M; Valentini, D; Khademi, M; Kockum, I; Lima, I; Arnheim-Dahlström, L; Lamb, F; Fink, K; Meng, Q; Kumar, A; Rane, L; Olsson, T; Maeurer, M

2015-09-01

Type 1 narcolepsy is a neurological disorder characterized by excessive daytime sleepiness and cataplexy associated with the HLA allele DQB1*06:02. Genetic predisposition along with external triggering factors may drive autoimmune responses, ultimately leading to the selective loss of hypocretin-positive neurons. The aim of this study was to investigate potential aetiological factors in Swedish cases of postvaccination (Pandemrix) narcolepsy defined by interferon-gamma (IFNγ) production from immune cells in response to molecularly defined targets. Cellular reactivity defined by IFNγ production was examined in blood from 38 (HLA-DQB1*06:02(+) ) Pandemrix-vaccinated narcolepsy cases and 76 (23 HLA-DQB1*06:02(+) and 53 HLA-DQB1*06:02(-) ) control subjects, matched for age, sex and exposure, using a variety of different antigens: β-haemolytic group A streptococcal (GAS) antigens (M5, M6 and streptodornase B), influenza (the pandemic A/H1N1/California/7/09 NYMC X-179A and A/H1N1/California/7/09 NYMC X-181 vaccine antigens, previous Flu-A and -B vaccine targets, A/H1N1/Brisbane/59/2007, A/H1N1/Solomon Islands/3/2006, A/H3N2/Uruguay/716/2007, A/H3N2/Wisconsin/67/2005, A/H5N1/Vietnam/1203/2004 and B/Malaysia/2506/2004), noninfluenza viral targets (CMVpp65, EBNA-1 and EBNA-3) and auto-antigens (hypocretin peptide, Tribbles homolog 2 peptide cocktail and extract from rat hypothalamus tissue). IFN-γ production was significantly increased in whole blood from narcolepsy cases in response to streptococcus serotype M6 (P = 0.0065) and streptodornase B protein (P = 0.0050). T-cell recognition of M6 and streptodornase B was confirmed at the single-cell level by intracellular cytokine (IL-2, IFNγ, tumour necrosis factor-alpha and IL-17) production after stimulation with synthetic M6 or streptodornase B peptides. Significantly, higher (P = 0.02) titres of serum antistreptolysin O were observed in narcolepsy cases, compared to vaccinated controls. β-haemolytic GAS may be

Intravenous immunoglobulin treatment and screening for hypocretin neuron-specific autoantibodies in recent onset childhood narcolepsy with cataplexy

DEFF Research Database (Denmark)

Knudsen, S; Mikkelsen, J D; Bang, B

2010-01-01

Narcolepsy with cataplexy (NC) is caused by substantial loss of hypocretin neurons. NC patients carry the HLA-DQB1*0602 allele suggesting that hypocretin neuron loss is due to an autoimmune attack. We tested intravenous immunoglobulin (IVIG) treatment in early onset NC....

Protective human leucocyte antigen haplotype, HLA-DRB1*01-B*14, against chronic Chagas disease in Bolivia.

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Florencia del Puerto

Full Text Available BACKGROUND: Chagas disease, caused by the flagellate parasite Trypanosoma cruzi affects 8-10 million people in Latin America. The mechanisms that underlie the development of complications of chronic Chagas disease, characterized primarily by pathology of the heart and digestive system, are not currently understood. To identify possible host genetic factors that may influence the clinical course of Chagas disease, Human Leucocyte Antigen (HLA regional gene polymorphism was analyzed in patients presenting with differing clinical symptoms. METHODOLOGY: Two hundred and twenty nine chronic Chagas disease patients in Santa Cruz, Bolivia, were examined by serological tests, electrocardiogram (ECG, and Barium enema colon X-ray. 31.4% of the examinees showed ECG alterations, 15.7% megacolon and 58.1% showed neither of them. A further 62 seropositive megacolon patients who had undergone colonectomy due to acute abdomen were recruited. We analyzed their HLA genetic polymorphisms (HLA-A, HLA-B, MICA, MICB, DRB1 and TNF-alpha promoter region mainly through Sequence based and LABType SSO typing test using LUMINEX Technology. PRINCIPAL FINDINGS: The frequencies of HLA-DRB1*01 and HLA-B*14:02 were significantly lower in patients suffering from megacolon as well as in those with ECG alteration and/or megacolon compared with a group of patients with indeterminate symptoms. The DRB1*0102, B*1402 and MICA*011 alleles were in strong Linkage Disequilibrium (LD, and the HLA-DRB1*01-B*14-MICA*011 haplotype was associated with resistance against chronic Chagas disease. CONCLUSIONS: This is the first report of HLA haplotype association with resistance to chronic Chagas disease.

HLA-DRB1 alleles associated with polymyalgia rheumatica in northern Italy: correlation with disease severity

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Salvarani, C.; Boiardi, L.; Mantovani, V.; Ranzi, A.; Cantini, F.; Olivieri, I.; Bragliani, M.; Collina, E.; Macchioni, P.

1999-01-01

OBJECTIVE—To examine the association of HLA-DRB1 alleles with polymyalgia rheumatica (PMR) in a Mediterranean country and to explore the role of HLA-DRB1 genes in determining disease severity.
METHODS—A five year prospective follow up study of 92 consecutive PMR patients diagnosed by the secondary referral centre of rheumatology of Reggio Emilia, Italy was conducted. HLA-DRB1 alleles were determined in the 92 patients, in 29 DR4 positive rheumatoid arthritis (RA) patients, and in 148 controls from the same geographical area by polymerase chain reaction amplification and oligonucleotide hybridisation.
RESULTS—No significant differences were observed in the frequencies of HLA-DRB1 types and in the expression of HLA-DRB 70-74 shared motif between PMR and controls. The frequency of the patients with double dose of epitope was low and not significantly different in PMR and in controls. No significant differences in the distribution of HLA-DR4 subtypes were observed between DR4+ PMR, DR+ RA, and DR4+ controls. Results of the univariate analysis indicated that an erythrocyte sedimentation rate (ESR) at diagnosis > 72 mm 1st h, the presence of HLA-DR1, DR10, rheumatoid epitope, and the type of rheumatoid epitope were significant risk factors associated with relapse/recurrence. Cox proportional hazards modelling identified two variables that independently increased the risk of relapse/recurrence: ESR at diagnosis > 72 mm 1st h (RR=1.5) and type 2 (encoded by a non-DR4 allele) rheumatoid epitope (RR=2.7).
CONCLUSION—These data from a Mediterranean country showed no association of rheumatoid epitope with PMR in northern Italian patients. A high ESR at diagnosis and the presence of rheumatoid epitope encoded by a non-DR4 allele are independent valuable markers of disease severity.

 PMID:10225816

Interaction between polymorphisms of the Human Leukocyte Antigen and HPV-16 Variants on the risk of invasive cervical cancer

International Nuclear Information System (INIS)

Araujo Souza, Patricia S de; Maciag, Paulo C; Ribeiro, Karina B; Petzl-Erler, Maria Luiza; Franco, Eduardo L; Villa, Luisa L

2008-01-01

Persistent infection with oncogenic types of human papillomavirus (HPV) is the major risk factor for invasive cervical cancer (ICC), and non-European variants of HPV-16 are associated with an increased risk of persistence and ICC. HLA class II polymorphisms are also associated with genetic susceptibility to ICC. Our aim is to verify if these associations are influenced by HPV-16 variability. We characterized HPV-16 variants by PCR in 107 ICC cases, which were typed for HLA-DQA1, DRB1 and DQB1 genes and compared to 257 controls. We measured the magnitude of associations by logistic regression analysis. European (E), Asian-American (AA) and African (Af) variants were identified. Here we show that inverse association between DQB1*05 (adjusted odds ratio [OR] = 0.66; 95% confidence interval [CI]: 0.39–1.12]) and HPV-16 positive ICC in our previous report was mostly attributable to AA variant carriers (OR = 0.27; 95%CI: 0.10–0.75). We observed similar proportions of HLA DRB1*1302 carriers in E-P positive cases and controls, but interestingly, this allele was not found in AA cases (p = 0.03, Fisher exact test). A positive association with DRB1*15 was observed in both groups of women harboring either E (OR = 2.99; 95% CI: 1.13–7.86) or AA variants (OR = 2.34; 95% CI: 1.00–5.46). There was an inverse association between DRB1*04 and ICC among women with HPV-16 carrying the 350T [83L] single nucleotide polymorphism in the E6 gene (OR = 0.27; 95% CI: 0.08–0.96). An inverse association between DQB1*05 and cases carrying 350G (83V) variants was also found (OR = 0.37; 95% CI: 0.15–0.89). Our results suggest that the association between HLA polymorphism and risk of ICC might be influenced by the distribution of HPV-16 variants

Chronic cerebrospinal vascular insufficiency is not associated with HLA DRB1*1501 status in multiple sclerosis patients.

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Bianca Weinstock-Guttman

Full Text Available BACKGROUND: Chronic cerebrospinal venous insufficiency (CCSVI was described as a vascular condition characterized by anomalies of veins outside the skull was reported to be associated with multiple sclerosis (MS. The objective was to assess the associations between HLA DRB1*1501 status and the occurrence of CCSVI in MS patients. METHODOLOGY/PRINCIPAL FINDINGS: This study included 423 of 499 subjects enrolled in the Combined Transcranial and Extracranial Venous Doppler Evaluation (CTEVD study. The HLA DRB1*1501 status was obtained in 268 MS patients and 155 controls by genotyping rs3135005, a SNP associated with DRB1*1501 status. All subjects underwent a clinical examination and Doppler scan of the head and neck. The frequency of CCSVI was higher (OR = 4.52, p<0.001 in the MS group 56.0% vs. 21.9% in the controls group and also higher in the progressive MS group 69.8% vs. 49.5% in the non-progressive MS group. The 51.9% frequency of HLA DRB1*1501 positivity (HLA(+ in MS was higher compared (OR = 2.33, p<0.001 to 31.6% to controls. The HLA(+ frequency in the non-progressive (51.6% and progressive MS groups (52.3% was similar. The frequency of HLA(+ CCSVI(+ was 40.7% in progressive MS, 27.5% in non-progressive MS and 8.4% in controls. The presence of CCSVI was independent of HLA DRB1*1501 status in MS patients. CONCLUSIONS/SIGNIFICANCE: The lack of strong associations of CCSVI with HLA DRB1*1501 suggests that the role of the underlying associations of CCSVI in MS should be interpreted with caution. Further longitudinal studies should determine whether interactions between these factors can contribute to disease progression in MS.

An Anti-C1s Monoclonal, TNT003, Inhibits Complement Activation Induced by Antibodies Against HLA.

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Thomas, K A; Valenzuela, N M; Gjertson, D; Mulder, A; Fishbein, M C; Parry, G C; Panicker, S; Reed, E F

2015-08-01

Antibody-mediated rejection (AMR) of solid organ transplants (SOT) is characterized by damage triggered by donor-specific antibodies (DSA) binding donor Class I and II HLA (HLA-I and HLA-II) expressed on endothelial cells. While F(ab')2 portions of DSA cause cellular activation and proliferation, Fc regions activate the classical complement cascade, resulting in complement deposition and leukocyte recruitment, both hallmark features of AMR. We characterized the ability of an anti-C1s monoclonal antibody, TNT003, to inhibit HLA antibody (HLA-Ab)-induced complement activation. Complement deposition induced by HLA-Ab was evaluated using novel cell- and bead-based assays. Human aortic endothelial cells (HAEC) were cultured with HLA-Ab and human complement; production of activated complement proteins was measured by flow cytometry. Additionally, C3d deposition was measured on single antigen beads (SAB) mixed with HLA-Ab and human complement. TNT003 inhibited HLA-Ab mediated complement deposition on HAEC in a concentration-dependent manner; C3a, C4a and C5a anaphylatoxin production was also diminished by TNT003. Finally, TNT003 blocked C3d deposition induced by Class I (HLAI-Ab)- and Class II (HLAII-Ab)-specific antibodies on SAB. These data suggest TNT003 may be useful for modulating the effects of DSA, as TNT003 inhibits complement deposition and split product formation generated by HLA-I/II-Ab in vitro. © 2015 The Authors. American Journal of Transplantation Published by Wiley Periodicals, Inc.

Microbiological, immunological and genetic factors in family members with periodontitis as a manifestation of systemic disease, associated with hematological disorders.

Science.gov (United States)

Okada, Mitsugi; Awane, Saori; Suzuki, Junji; Hino, Takamune; Takemoto, Toshinobu; Kurihara, Hidemi; Miura, Kazuo

2002-08-01

The microflora, immunological profiles of host defence functions, and human leukocyte antigen (HLA) findings are reported for a mother, son and daughter who were diagnosed as having 'periodontitis as a manifestation of systemic diseases, associated with hematological disorders'. Examinations were made of the bacterial flora from the periodontal pocket, neutrophil chemotaxis, neutrophil phagocytosis, and the genotypes (DQB1) and serotypes (DR locus) of HLA class II antigens. Phenotypic analyses of the peripheral lymphocytes were also conducted. The subgingival microflora from the mother was dominated by Gram-negative rods, especially Porphyromonas endodontalis, Prevotella intermedia/Prevotella nigrescens and Fusobacterium nucleatum. Subgingival microflora samples from the son and daughter were dominated by Gram-positive cocci and Gram-positive rods. Through the use of polymerase chain reaction, Campylobacter rectus and Capnocytophaga gingivalis were detected in all subjects, whereas Porphyromonas gingivalis, P. intermedia, and Treponema denticola were not detected in any subjects. All three subjects showed a remarkable level of depressed neutrophil chemotaxis to N-formyl-methionyl-leucyl-phenylalanine, although their phagocyte function levels were normal, in comparison to healthy control subjects. Each subject had the same genotype, HLA-DQB1*0601, while the mother had HLA-DR2 and HLA-DR8, and the son and daughter had HLA-DR2 only. In summary, the members of this family showed a similar predisposition to periodontitis with regard to certain host defence functions. It is suggested that the depressed neutrophil chemotaxis that was identified here could be a significant risk factor for periodontitis in this family.

HLA-DPB1 typing with polymerase chain reaction and restriction fragment length polymorphism technique in Danes

DEFF Research Database (Denmark)

Hviid, Thomas Vauvert F.; Madsen, Hans O; Morling, Niels

1992-01-01

We have used the polymerase chain reaction (PCR) in combination with the restriction fragment length polymorphism (RFLP) technique for HLA-DBP1 typing. After PCR amplification of the polymorphic second exon of the HLA-DPB1 locus, the PCR product was digested with seven allele-specific restriction...... endonucleases: RsaI, FokI, ApaI, SacI, BstUI, EcoNI, and DdeI, and the DNA fragments were separated by electrophoresis in agarose gels. Altogether, 71 individuals were investigated and 16 different HLA-DPB1 types were observed in 26 different heterozygotic combinations, as well as five possible homozygotes....... Four heterozygotes could not be unequivocally typed with the PCR-RFLP method. The HLA-DPB1 typing results obtained with the PCR-RFLP method were compared with the typing results obtained with PCR allele-specific oligonucleotides (PCR-ASO) in 50 individuals. The results obtained with the two methods...

HLA-G molecule as inductor of immunotolerance

International Nuclear Information System (INIS)

Alfonso Valdes, Maria E

2009-01-01

HLA-G are molecules are (non-classic) class I antigens from main histocompatibility system. There are sis isoforms of HLA-G antigen codifying four proteins united to a membrane (HLA-G1, HLA-G2, HLA-G3, HLA-G4), and three soluble isoforms (HLA-G5, HLA-G6, HLA-G7). The first ones are expressed in cells of placental extravillous cytotrophoblast (Langhans' layer), amnios epithelial cells, fetal endothelial cells, mesenchymal macrophages of chorionic villi, and in epithelial cells of thymus medulla; the second ones in amniotic fluid, in maternal peripheral blood and that of the umbilical cord. There was a HLA-G expression in some types of tumors, stroma cells under inflammation conditions, virus-infected cells and in serum of transplant patients. There are strong evidences of HLA-G molecules role in tolerance induction to these physiological and pathological situations through suppression of lithic activity of NK cells and of cytotoxic T lymphocytes. This knowledge may be very useful in future therapeutical management of these entities as well as to favor the success of tissue and organ transplant

HLA class I antigen processing machinery (APM) component expression and PD-1:PD-L1 pathway activation in HIV-infected head and neck cancers.

Science.gov (United States)

Pai, Sara I; Jack Lee, J; Carey, Thomas E; Westra, William H; Ferrone, Soldano; Moore, Charles; Mosunjac, Marina B; Shin, Dong M; Ferris, Robert L

2018-02-01

Human immunodeficiency virus (HIV)-infected individuals are at increased risk for developing several non-AIDS related malignancies and are often excluded from cancer immunotherapy regimens. To evaluate the immune competence of this cancer patient population, we evaluated HLA class I antigen presenting machinery (APM) component expression and PD-1:PD-L1 pathway upregulation in HIV(+) and HIV(-) head and neck cancers (HNCs). Sixty-two HIV(+) and 44 matched HIV(-) controls diagnosed with HNC between 1991 and 2011 from five tertiary care referral centers in the United States were identified. HLA class I APM component, PD-1, and PD-L1 expression were analyzed by immunohistochemical staining with monoclonal antibodies (mAbs). Clinical data was abstracted from the medical records. There was no significant difference between the cases and controls in LMP2, TAP1, HLA-A and HLA-B/C, as well as PD-1 and PD-L1 expression. Overall, 62% of all subjects had high PD-1 expression and 82% of the subjects expressed PD-L1 within the tumor microenvironment. LMP2, HLA-A and HLA-B/C expression were significantly associated with moderate to high PD-1 expression in the HIV(+) HNC cases (p = .004, p = .026, and p = .006, respectively) but not in the HIV(-) controls. In addition, HLA-A expression was significantly associated with PD-L1 expression in the HIV(+) HNC cases only (p = .029). HIV-infected individuals diagnosed with HNC do not have any detectable defects in HLA class I APM component expression and in PD-1:PD-L1 pathway activation. Given the current successes of HAART therapy in maintaining immune cell counts, HIV(+) patients diagnosed with cancer may benefit from the recently FDA-approved immune checkpoint blockade therapy. Copyright © 2017 Elsevier Ltd. All rights reserved.

Superantigen and HLA-DR ligation induce phospholipase-C gamma 1 activation in class II+ T cells

DEFF Research Database (Denmark)

Kanner, S B; Odum, Niels; Grosmaire, L

1992-01-01

Bacterial enterotoxin superantigens bind directly to HLA class II molecules (HLA-DR) expressed on both APC and activated human T cells, and simultaneously bind to certain V beta chains of the TCR. In this report, we compared early T cell signaling events in human alloantigen-stimulated T cells when...... activated by HLA-DR ligation through antibody cross-linking or by direct enterotoxin superantigen binding. Both types of stimuli induced tyrosine phosphorylation of phosphatidylinositol-specific phospholipase C gamma 1 (PLC gamma 1) and an increase in intracellular calcium concentration; however......, superantigen-induced signaling was stronger than class II ligation alone. Antibody-mediated ligation of HLA-DR with CD3 resulted in augmented PLC gamma 1 activation and increased calcium mobilization, consistent with a mechanism of superantigen activity through a combination of class II and CD3/Ti signals...

[Interaction between HLA-DRB1 gene polymorphism and environmental risk factors in the development of gestational diabetes mellitus].

Science.gov (United States)

Wang, Ming; Zhang, Li; Liu, Xinghui

2014-04-01

To explore the interactions between human leukocyte antigen (HLA) -DRB1 gene polymorphism and environmental risk factors in gestational diabetes mellitus (GDM) pathogenesis. Pregnant women who had prenatal cares in Obstetric Department, West China Second Hospital of Sichuan University were recruited from January 1(st) to December 31(st) in 2011. A prospective cohort study was conducted in the women who had a glucose challenge test (GCT) or 75 g oral glucose tolerance test (OGTT) during 24-28 gestational weeks. A total of 104 women diagnosed with GDM were randomly included in GDM group while another 103 normal women fell into the control group. The HLA-DRB1 polymorphism was detected by Polymerase Chain Reaction - Sequence Specific Primers (PCR-SSP) method in both groups. The interactions between HLA-DRB1 polymorphism and environmental risk factors were analyzed based on the simple-case-study method. (1) There were 712 pregnant women with complete perinatal information during January 1(st) to December 31(st) , 2011, among whom 175 (24.6%) women were diagnosed with GDM. A logistic regression analysis showed that advanced maternal age (OR = 1.081, 95%CI: 1.027- 1.138), imbalanced diet (OR = 3.329, 95%CI: 2.167-5.116), high body mass index (BMI ≥ 24.0 kg/m(2)) before pregnancy (OR = 1.095, 95%CI:1.008-1.190), HBsAg carrier status (OR = 3.173, 95%CI: 1.387-7.260) and family history of diabetes mellitus (DM) (OR = 1.798, 95%CI: 1.063-3.041) were risk factors of GDM. (2) There were 49 HLA-DRB1 genotypes and 51 HLA-DRB1 genotypes in GDM group and the control group, respectively. We further compared the genotypes that occurred in over 3 cases in either group and found that HLA-DRB1*12, 16 was only detected in 5 cases (5/103, 4.9%) in control group, and the difference was significant between the two groups (P = 0.029). HLA-DRB1*11, 16 and HLA-DRB1*09,09 were only detected in 4 cases (3.8%, 4/104) and 5 cases (4.8%, 5/104) in GDM group respectively, but without significant

Journal of Biosciences | Indian Academy of Sciences

Indian Academy of Sciences (India)

Standard methods of serological HLA typing, ABO and Rh (D) groups, and screening for Rh D antibodies were used. 392 unrelated individuals from the population were compared as controls. In addition 45 unrelated individuals from the same population were typed for HLA DRB and DQB gene using PCR-SSP kits.

Susceptibility to aplastic anemia is associated with HLA-DRB1*1501 in an aboriginal population in Sabah, Malaysia.

Science.gov (United States)

Dhaliwal, J S; Wong, Lily; Kamaluddin, Muhammad Amir; Yin, Lee Yin; Murad, Shahnaz

2011-10-01

The incidence of aplastic anemia is reported to be higher in Asia than elsewhere. We studied the frequency of human leukocyte antigen (HLA) DRB1 alleles in aplastic anemia patients from 2 genetically similar aboriginal groups, the Kadazan and the Dusun, and compared them with genetically matched community and hospital controls. HLA-DRB1*15 was significantly higher in the patients compared with controls (p = 0.005), confirming similar findings in Japanese and Caucasian studies. Further testing indicated a significantly higher frequency of HLA-DRB1*1501 in patients compared with controls (p = 0.0004) but no significant difference in the frequency of HLA-DRB1*1502. The high frequency of HLA-DRB1*15 in the Kadazan and Dusun population combined with the wide variety of environmental factors associated with aplastic anemia could be the reason for the elevated incidence of aplastic anemia in the Kadazan and Dusun in Sabah. Copyright © 2011 American Society for Histocompatibility and Immunogenetics. Published by Elsevier Inc. All rights reserved.

Moving beyond HLA: a review of nHLA antibodies in organ transplantation.

Science.gov (United States)

Sigdel, Tara K; Sarwal, Minnie M

2013-11-01

Given the finite graft life expectancy of HLA identical organ transplants and the recognition of humoral graft injury in the absence of donor directed anti-HLA antibodies, the clinical impact of antibodies against non-HLA (nHLA) antigens in transplant injury is being increasingly recognized. The recognition of the impact of nHLA antigen discrepancies between donor and recipient on transplant outcomes is timely given the advances in rapid and lower cost sequencing methods that can soon provide complete maps of all recipient and donor HLA and nHLA mismatch data. In this review, we present a summary of recent reports evaluating the role of nHLA antibodies and their relevance to the field of organ transplantation. Copyright © 2013 American Society for Histocompatibility and Immunogenetics. Published by Elsevier Inc. All rights reserved.

Protective Effect of HLA-B*5701 and HLA-C -35 Genetic Variants in HIV-Positive Caucasians from Northern Poland.

Directory of Open Access Journals (Sweden)

Magdalena Leszczyszyn-Pynka

Full Text Available Association of two HLA class I variants with HIV-1 pretreatment viremia, CD4+ T cell count at the care-entry and CD4+ T cell nadir.414 HIV-positive Caucasians (30% women aged 19-73 years were genotyped for HLA-C -35 (rs9264942 and HLA-B*5701 variants. HIV-1 viral load, as well as CD4+ T cell count at care-entry and nadir, were compared across alleles, genotypes and haplotypes.HLA-C -35 C/C genotype was found in 17.6% patients, C/T genotype in 48.1%, and T/T genotype in 34.3% patients. HLA-B*5701 variant was present in 5.8% of studied population. HIV plasma viremia in the group with C allele was significantly lower (p=0.0002 compared to T/T group [mean:4.66 log (SD:1.03 vs. 5.07 (SD:0.85 log HIV-RNA copies/ml, respectively], while CD4+ T cell count at baseline was notably higher among C allele carriers compared to T/T homozygotes [median: 318 (IQR:127-537 cells/μl vs. median: 203 (IQR:55-410 cells/μl, respectively] (p=0.0007. Moreover, CD4+ T cell nadir among patients with C allele [median: 205 (IQR:83.5-390 cells/μl] was significantly higher compared to T/T group [median: 133 (IQR:46-328 cells/μl] (p=0.006. Among cases with HLA-B*5701 allele, significantly lower pretreatment viremia and higher baseline CD4+ T cell count were found (mean: 4.08 [SD: 1.2] vs. mean: 4.84 [SD:0.97] log HIV-RNA copies/ml, p=0.003 and 431 vs. 270 cells/μl, p=0.04, respectively compared to HLA-B*5701 negative individuals. The lowest viremia (mean: 3.85 log [SD:1.3] HIV-RNA copies/ml and the highest baseline and nadir CD4+ T cell [median: 476 (IQR:304-682 vs. median: 361 (IQR: 205-574 cells/μl, respectively were found in individuals with HLA-B*5701(+/HLA-C -35 C/C haplotype.HLA-C -35 C and HLA-B*5701 allele exert a favorable effect on the immunological (higher baseline and nadir CD4+ T cell count and virologic (lower pretreatment HIV viral load variables. This protective effect is additive for the compound HLA-B*5701(+/HLA-C -35 C/C haplotype.

Non HLA genetic markers association with type-1 diabetes mellitus ...

African Journals Online (AJOL)

The currently available data identified IDDM1 and IDDM2 as 2 susceptibility loci for type 1 diabetes (T1D). The major histocompatibility complex (MHC)/HLA region referred to as IDDM1 contains several 100 genes known to have a great influence on T1D risk. Within IDDM2, a minisatellite variable number of tandem repeats ...

Discovery of new risk loci for IgA nephropathy implicates genes involved in immunity against intestinal pathogens

Science.gov (United States)

Kiryluk, Krzysztof; Li, Yifu; Scolari, Francesco; Sanna-Cherchi, Simone; Choi, Murim; Verbitsky, Miguel; Fasel, David; Lata, Sneh; Prakash, Sindhuri; Shapiro, Samantha; Fischman, Clara; Snyder, Holly J.; Appel, Gerald; Izzi, Claudia; Viola, Battista Fabio; Dallera, Nadia; Vecchio, Lucia Del; Barlassina, Cristina; Salvi, Erika; Bertinetto, Francesca Eleonora; Amoroso, Antonio; Savoldi, Silvana; Rocchietti, Marcella; Amore, Alessandro; Peruzzi, Licia; Coppo, Rosanna; Salvadori, Maurizio; Ravani, Pietro; Magistroni, Riccardo; Ghiggeri, Gian Marco; Caridi, Gianluca; Bodria, Monica; Lugani, Francesca; Allegri, Landino; Delsante, Marco; Maiorana, Mariarosa; Magnano, Andrea; Frasca, Giovanni; Boer, Emanuela; Boscutti, Giuliano; Ponticelli, Claudio; Mignani, Renzo; Marcantoni, Carmelita; Di Landro, Domenico; Santoro, Domenico; Pani, Antonello; Polci, Rosaria; Feriozzi, Sandro; Chicca, Silvana; Galliani, Marco; Gigante, Maddalena; Gesualdo, Loreto; Zamboli, Pasquale; Maixnerová, Dita; Tesar, Vladimir; Eitner, Frank; Rauen, Thomas; Floege, Jürgen; Kovacs, Tibor; Nagy, Judit; Mucha, Krzysztof; Pączek, Leszek; Zaniew, Marcin; Mizerska-Wasiak, Małgorzata; Roszkowska-Blaim, Maria; Pawlaczyk, Krzysztof; Gale, Daniel; Barratt, Jonathan; Thibaudin, Lise; Berthoux, Francois; Canaud, Guillaume; Boland, Anne; Metzger, Marie; Panzer, Ulf; Suzuki, Hitoshi; Goto, Shin; Narita, Ichiei; Caliskan, Yasar; Xie, Jingyuan; Hou, Ping; Chen, Nan; Zhang, Hong; Wyatt, Robert J.; Novak, Jan; Julian, Bruce A.; Feehally, John; Stengel, Benedicte; Cusi, Daniele; Lifton, Richard P.; Gharavi, Ali G.

2014-01-01

We performed a genome-wide association study (GWAS) of IgA nephropathy (IgAN), the most common form of glomerulonephritis, with discovery and follow-up in 20,612 individuals of European and East Asian ancestry. We identified six novel genome-wide significant associations, four in ITGAM-ITGAX, VAV3 and CARD9 and two new independent signals at HLA-DQB1 and DEFA. We replicated the nine previously reported signals, including known SNPs in the HLA-DQB1 and DEFA loci. The cumulative burden of risk alleles is strongly associated with age at disease onset. Most loci are either directly associated with risk of inflammatory bowel disease (IBD) or maintenance of the intestinal epithelial barrier and response to mucosal pathogens. The geo-spatial distribution of risk alleles is highly suggestive of multi-locus adaptation and the genetic risk correlates strongly with variation in local pathogens, particularly helminth diversity, suggesting a possible role for host-intestinal pathogen interactions in shaping the genetic landscape of IgAN. PMID:25305756

The Major Genetic Determinants of HIV-1 Control Affect HLA Class I Peptide Presentation

Science.gov (United States)

Pereyra, Florencia; Jia, Xiaoming; McLaren, Paul J.; Telenti, Amalio; de Bakker, Paul I.W.; Walker, Bruce D.; Jia, Xiaoming; McLaren, Paul J.; Ripke, Stephan; Brumme, Chanson J.; Pulit, Sara L.; Telenti, Amalio; Carrington, Mary; Kadie, Carl M.; Carlson, Jonathan M.; Heckerman, David; de Bakker, Paul I.W.; Pereyra, Florencia; de Bakker, Paul I.W.; Graham, Robert R.; Plenge, Robert M.; Deeks, Steven G.; Walker, Bruce D.; Gianniny, Lauren; Crawford, Gabriel; Sullivan, Jordan; Gonzalez, Elena; Davies, Leela; Camargo, Amy; Moore, Jamie M.; Beattie, Nicole; Gupta, Supriya; Crenshaw, Andrew; Burtt, Noël P.; Guiducci, Candace; Gupta, Namrata; Carrington, Mary; Gao, Xiaojiang; Qi, Ying; Yuki, Yuko; Pereyra, Florencia; Piechocka-Trocha, Alicja; Cutrell, Emily; Rosenberg, Rachel; Moss, Kristin L.; Lemay, Paul; O’Leary, Jessica; Schaefer, Todd; Verma, Pranshu; Toth, Ildiko; Block, Brian; Baker, Brett; Rothchild, Alissa; Lian, Jeffrey; Proudfoot, Jacqueline; Alvino, Donna Marie L.; Vine, Seanna; Addo, Marylyn M.; Allen, Todd M.; Altfeld, Marcus; Henn, Matthew R.; Le Gall, Sylvie; Streeck, Hendrik; Walker, Bruce D.; Haas, David W.; Kuritzkes, Daniel R.; Robbins, Gregory K.; Shafer, Robert W.; Gulick, Roy M.; Shikuma, Cecilia M.; Haubrich, Richard; Riddler, Sharon; Sax, Paul E.; Daar, Eric S.; Ribaudo, Heather J.; Agan, Brian; Agarwal, Shanu; Ahern, Richard L.; Allen, Brady L.; Altidor, Sherly; Altschuler, Eric L.; Ambardar, Sujata; Anastos, Kathryn; Anderson, Ben; Anderson, Val; Andrady, Ushan; Antoniskis, Diana; Bangsberg, David; Barbaro, Daniel; Barrie, William; Bartczak, J.; Barton, Simon; Basden, Patricia; Basgoz, Nesli; Bazner, Suzane; Bellos, Nicholaos C.; Benson, Anne M.; Berger, Judith; Bernard, Nicole F.; Bernard, Annette M.; Birch, Christopher; Bodner, Stanley J.; Bolan, Robert K.; Boudreaux, Emilie T.; Bradley, Meg; Braun, James F.; Brndjar, Jon E.; Brown, Stephen J.; Brown, Katherine; Brown, Sheldon T.; Burack, Jedidiah; Bush, Larry M.; Cafaro, Virginia; Campbell, Omobolaji; Campbell, John; Carlson, Robert H.; Carmichael, J. Kevin; Casey, Kathleen K.; Cavacuiti, Chris; Celestin, Gregory; Chambers, Steven T.; Chez, Nancy; Chirch, Lisa M.; Cimoch, Paul J.; Cohen, Daniel; Cohn, Lillian E.; Conway, Brian; Cooper, David A.; Cornelson, Brian; Cox, David T.; Cristofano, Michael V.; Cuchural, George; Czartoski, Julie L.; Dahman, Joseph M.; Daly, Jennifer S.; Davis, Benjamin T.; Davis, Kristine; Davod, Sheila M.; Deeks, Steven G.; DeJesus, Edwin; Dietz, Craig A.; Dunham, Eleanor; Dunn, Michael E.; Ellerin, Todd B.; Eron, Joseph J.; Fangman, John J.W.; Farel, Claire E.; Ferlazzo, Helen; Fidler, Sarah; Fleenor-Ford, Anita; Frankel, Renee; Freedberg, Kenneth A.; French, Neel K.; Fuchs, Jonathan D.; Fuller, Jon D.; Gaberman, Jonna; Gallant, Joel E.; Gandhi, Rajesh T.; Garcia, Efrain; Garmon, Donald; Gathe, Joseph C.; Gaultier, Cyril R.; Gebre, Wondwoosen; Gilman, Frank D.; Gilson, Ian; Goepfert, Paul A.; Gottlieb, Michael S.; Goulston, Claudia; Groger, Richard K.; Gurley, T. Douglas; Haber, Stuart; Hardwicke, Robin; Hardy, W. David; Harrigan, P. Richard; Hawkins, Trevor N.; Heath, Sonya; Hecht, Frederick M.; Henry, W. Keith; Hladek, Melissa; Hoffman, Robert P.; Horton, James M.; Hsu, Ricky K.; Huhn, Gregory D.; Hunt, Peter; Hupert, Mark J.; Illeman, Mark L.; Jaeger, Hans; Jellinger, Robert M.; John, Mina; Johnson, Jennifer A.; Johnson, Kristin L.; Johnson, Heather; Johnson, Kay; Joly, Jennifer; Jordan, Wilbert C.; Kauffman, Carol A.; Khanlou, Homayoon; Killian, Robert K.; Kim, Arthur Y.; Kim, David D.; Kinder, Clifford A.; Kirchner, Jeffrey T.; Kogelman, Laura; Kojic, Erna Milunka; Korthuis, P. Todd; Kurisu, Wayne; Kwon, Douglas S.; LaMar, Melissa; Lampiris, Harry; Lanzafame, Massimiliano; Lederman, Michael M.; Lee, David M.; Lee, Jean M.L.; Lee, Marah J.; Lee, Edward T.Y.; Lemoine, Janice; Levy, Jay A.; Llibre, Josep M.; Liguori, Michael A.; Little, Susan J.; Liu, Anne Y.; Lopez, Alvaro J.; Loutfy, Mono R.; Loy, Dawn; Mohammed, Debbie Y.; Man, Alan; Mansour, Michael K.; Marconi, Vincent C.; Markowitz, Martin; Marques, Rui; Martin, Jeffrey N.; Martin, Harold L.; Mayer, Kenneth Hugh; McElrath, M. Juliana; McGhee, Theresa A.; McGovern, Barbara H.; McGowan, Katherine; McIntyre, Dawn; Mcleod, Gavin X.; Menezes, Prema; Mesa, Greg; Metroka, Craig E.; Meyer-Olson, Dirk; Miller, Andy O.; Montgomery, Kate; Mounzer, Karam C.; Nagami, Ellen H.; Nagin, Iris; Nahass, Ronald G.; Nelson, Margret O.; Nielsen, Craig; Norene, David L.; O’Connor, David H.; Ojikutu, Bisola O.; Okulicz, Jason; Oladehin, Olakunle O.; Oldfield, Edward C.; Olender, Susan A.; Ostrowski, Mario; Owen, William F.; Pae, Eunice; Parsonnet, Jeffrey; Pavlatos, Andrew M.; Perlmutter, Aaron M.; Pierce, Michael N.; Pincus, Jonathan M.; Pisani, Leandro; Price, Lawrence Jay; Proia, Laurie; Prokesch, Richard C.; Pujet, Heather Calderon; Ramgopal, Moti; Rathod, Almas; Rausch, Michael; Ravishankar, J.; Rhame, Frank S.; Richards, Constance Shamuyarira; Richman, Douglas D.; Robbins, Gregory K.; Rodes, Berta; Rodriguez, Milagros; Rose, Richard C.; Rosenberg, Eric S.; Rosenthal, Daniel; Ross, Polly E.; Rubin, David S.; Rumbaugh, Elease; Saenz, Luis; Salvaggio, Michelle R.; Sanchez, William C.; Sanjana, Veeraf M.; Santiago, Steven; Schmidt, Wolfgang; Schuitemaker, Hanneke; Sestak, Philip M.; Shalit, Peter; Shay, William; Shirvani, Vivian N.; Silebi, Vanessa I.; Sizemore, James M.; Skolnik, Paul R.; Sokol-Anderson, Marcia; Sosman, James M.; Stabile, Paul; Stapleton, Jack T.; Starrett, Sheree; Stein, Francine; Stellbrink, Hans-Jurgen; Sterman, F. Lisa; Stone, Valerie E.; Stone, David R.; Tambussi, Giuseppe; Taplitz, Randy A.; Tedaldi, Ellen M.; Telenti, Amalio; Theisen, William; Torres, Richard; Tosiello, Lorraine; Tremblay, Cecile; Tribble, Marc A.; Trinh, Phuong D.; Tsao, Alice; Ueda, Peggy; Vaccaro, Anthony; Valadas, Emilia; Vanig, Thanes J.; Vecino, Isabel; Vega, Vilma M.; Veikley, Wenoah; Wade, Barbara H.; Walworth, Charles; Wanidworanun, Chingchai; Ward, Douglas J.; Warner, Daniel A.; Weber, Robert D.; Webster, Duncan; Weis, Steve; Wheeler, David A.; White, David J.; Wilkins, Ed; Winston, Alan; Wlodaver, Clifford G.; Wout, Angelique van’t; Wright, David P.; Yang, Otto O.; Yurdin, David L.; Zabukovic, Brandon W.; Zachary, Kimon C.; Zeeman, Beth; Zhao, Meng

2011-01-01

Infectious and inflammatory diseases have repeatedly shown strong genetic associations within the major histocompatibility complex (MHC); however, the basis for these associations remains elusive. To define host genetic effects on the outcome of a chronic viral infection, we performed genome-wide association analysis in a multiethnic cohort of HIV-1 controllers and progressors, and we analyzed the effects of individual amino acids within the classical human leukocyte antigen (HLA) proteins. We identified >300 genome-wide significant single-nucleotide polymorphisms (SNPs) within the MHC and none elsewhere. Specific amino acids in the HLA-B peptide binding groove, as well as an independent HLA-C effect, explain the SNP associations and reconcile both protective and risk HLA alleles. These results implicate the nature of the HLA–viral peptide interaction as the major factor modulating durable control of HIV infection. PMID:21051598

HLA-A, -B, -DRB1 allele and haplotype frequencies of 920 cord blood units from Central Chile.

Science.gov (United States)

Schäfer, Christian; Sauter, Jürgen; Riethmüller, Tobias; Kashi, Zahra Mehdizadeh; Schmidt, Alexander H; Barriga, Francisco J

2016-08-01

We present human leukocyte antigen (HLA) haplotype and allele/antigenic group frequencies derived from a data set of 920 umbilical cord blood units collected in Central Chile. HLA-A and -B genotypes were typed using sequence specific oligonucleotide probe methods while HLA-DRB1 genotypes were obtained from sequencing-based typing. The most frequent haplotype is A*29~B*44~DRB1*07:01 with an estimated frequency of 2.1%. Copyright © 2016 American Society for Histocompatibility and Immunogenetics. Published by Elsevier Inc. All rights reserved.

[Correlation between HLA-DB1 genes and susceptibility to echinococcosis in Tibetan population in Tibetan Plateau].

Science.gov (United States)

Shu-Feng, Gao; Xiu-Min, Han; Xue-Fei, Zhang; Yong-Shun, Wang; Wei, Wang; Ya-Min, Guo; Yong-Shou, Li

2017-10-23

To determine the susceptibility genes and resistance genes in HLA-DRB1 alleles in Tibetan patients with cystic and alveolar hydatid diseases, so as to provide the references for the research of the genetic characteristics and infection mechanism of Tibetan hydatid diseases. The case control method was applied. The Tibetan patients with cystic and alveolar hydatid diseases (63 and 73 cases respectively) in Yushu and Guoluo Tibetan Autonomous Prefecture, and unrelated healthy people (60 cases) in this area were selected as the study subjects. The polymerase chain reaction-sequence based typing (PCR-SBT) technique was applied for genotyping of HLA-DRB1, and the comparison of the gene frequency. The frequency of HLA-DRB1*04 in the alveolar/cystic echinococcosis group was lower than that in the control group ( χ 2 = 4.71, 4.31, both P < 0.05). HLA-DRB1*04 genotypes may be associated with the resistance of cystic and alveolar echinococcosis and its resistance genes.

HIV-1 Control by NK Cells via Reduced Interaction between KIR2DL2 and HLA-C∗12:02/C∗14:03.

Science.gov (United States)

Lin, Zhansong; Kuroki, Kimiko; Kuse, Nozomi; Sun, Xiaoming; Akahoshi, Tomohiro; Qi, Ying; Chikata, Takayuki; Naruto, Takuya; Koyanagi, Madoka; Murakoshi, Hayato; Gatanaga, Hiroyuki; Oka, Shinichi; Carrington, Mary; Maenaka, Katsumi; Takiguchi, Masafumi

2016-11-22

Natural killer (NK) cells control viral infection in part through the interaction between killer cell immunoglobulin-like receptors (KIRs) and their human leukocyte antigen (HLA) ligands. We investigated 504 anti-retroviral (ART)-free Japanese patients chronically infected with HIV-1 and identified two KIR/HLA combinations, KIR2DL2/HLA-C ∗ 12:02 and KIR2DL2/HLA-C ∗ 14:03, that impact suppression of HIV-1 replication. KIR2DL2 + NK cells suppressed viral replication in HLA-C ∗ 14:03 + or HLA-C ∗ 12:02 + cells to a significantly greater extent than did KIR2DL2 - NK cells in vitro. Functional analysis showed that the binding between HIV-1-derived peptide and HLA-C ∗ 14:03 or HLA-C ∗ 12:02 influenced KIR2DL2 + NK cell activity through reduced expression of the peptide-HLA (pHLA) complex on the cell surface (i.e., reduced KIR2DL2 ligand expression), rather than through reduced binding affinity of KIR2DL2 to the respective pHLA complexes. Thus, KIR2DL2/HLA-C ∗ 12:02 and KIR2DL2/HLA-C ∗ 14:03 compound genotypes have protective effects on control of HIV-1 through a mechanism involving KIR2DL2-mediated NK cell recognition of virus-infected cells, providing additional understanding of NK cells in HIV-1 infection. Copyright © 2016 The Author(s). Published by Elsevier Inc. All rights reserved.

Quantitative Trait Locus and Brain Expression of HLA-DPA1 Offers Evidence of Shared Immune Alterations in Psychiatric Disorders

Directory of Open Access Journals (Sweden)

Ling Z. Morgan

2016-03-01

Full Text Available Genome-wide association studies of schizophrenia encompassing the major histocompatibility locus (MHC were highly significant following genome-wide correction. This broad region implicates many genes including the MHC complex class II. Within this interval we examined the expression of two MHC II genes (HLA-DPA1 and HLA-DRB1 in brain from individual subjects with schizophrenia (SZ, bipolar disorder (BD, major depressive disorder (MDD, and controls by differential gene expression methods. A third MHC II mRNA, CD74, was studied outside of the MHC II locus, as it interacts within the same immune complex. Exon microarrays were performed in anterior cingulate cortex (ACC in BD compared to controls, and both HLA-DPA1 and CD74 were decreased in expression in BD. The expression of HLA-DPA1 and CD74 were both reduced in hippocampus, amygdala, and dorsolateral prefrontal cortex regions in SZ and BD compared to controls by specific qPCR assay. We found several novel HLA-DPA1 mRNA variants spanning HLA-DPA1 exons 2-3-4 as suggested by exon microarrays. The intronic rs9277341 SNP was a significant cis expression quantitative trait locus (eQTL that was associated with the total expression of HLA-DPA1 in five brain regions. A biomarker study of MHC II mRNAs was conducted in SZ, BD, MDD, and control lymphoblastic cell lines (LCL by qPCR assay of 87 subjects. There was significantly decreased expression of HLA-DPA1 and CD74 in BD, and trends for reductions in SZ in LCLs. The discovery of multiple splicing variants in brain for HLA-DPA1 is important as the HLA-DPA1 gene is highly conserved, there are no reported splicing variants, and the functions in brain are unknown. Future work on the function and localization of MHC Class II proteins in brain will help to understand the role of alterations in neuropsychiatric disorders. The HLA-DPA1 eQTL is located within a large linkage disequilibrium block that has an irrefutable association with schizophrenia. Future

Molecular Characterization of Expressed DQA and DQB Genes in the California Sea Lion (Zalophus Californianus)

National Research Council Canada - National Science Library

Bowen, Lizabeth

2002-01-01

.... Five unique Zaca-DQA sequences and eight unique Zaca-DQB sequences, all encoding functional proteins, were identified in the two animals, indicating the presence of multiple DQ- loci in this species...

Traffic Generator (TrafficGen) Version 1.4.2: Users Guide

Science.gov (United States)

2016-06-01

the network with Transmission Control Protocol and User Datagram Protocol Internet Protocol traffic. Each node generating network traffic in an...TrafficGen Graphical User Interface (GUI) 3 3.1 Anatomy of the User Interface 3 3.2 Scenario Configuration and MGEN Files 4 4. Working with...for public release; distribution is unlimited. vi List of Figures Fig. 1 TrafficGen user interface

Focal epithelial hyperplasia associated with human papillomavirus 13 and common human leukocyte antigen alleles in a Turkish family.

Science.gov (United States)

Akoğlu, Gülşen; Metin, Ahmet; Ceylan, Gülay Güleç; Emre, Selma; Akpolat, Demet; Süngü, Nuran

2015-02-01

Focal epithelial hyperplasia (FEH) is a rare and benign papillomatous disease of the oral cavity, which is closely associated with human papillomavirus (HPV) type 13 and 32. Genetic susceptibility to HPV infections are supported by recent studies involving the human leukocyte antigen system (HLA). In this report, we aimed to determine the clinicopathological features of a Turkish family with FEH and to detect the shared HLA DR and DQ types. HPV DNA typing of tissue samples and HLA determination from blood samples of four family members were performed by polymerase chain reaction. Histopathological examination of all patients revealed acanthotic papillomatous epidermis, koilocytes, apoptotic keratinocytes, and mitosoid bodies. HPV13 was detected by polymerase chain reaction. HLA DQA1*0501, HLA DQB1*0302, and HLA DRB1*11 alleles were common in all family members. HLA DRB1*04 was detected in three of them. This report is the first step for the investigation of involvement of HLA types in the pathogenesis of Turkish patients with FEH. © 2014 The International Society of Dermatology.

Human leukocyte antigen (HLA)-G during pregnancy part I

DEFF Research Database (Denmark)

Klitkou, Louise; Dahl, Mette; Hviid, Thomas Vauvert F

2015-01-01

Human leukocyte antigen (HLA)-G is a class Ib molecule with restricted tissue distribution expressed on trophoblast cells and has been proposed to have immunomodulatory functions during pregnancy. Soluble HLA-G1 (sHLA-G1) can be generated by the shedding of membrane-bound HLA-G molecules; however...... of importance for production of sHLA-G in the mother and child, or it may support the theory that sHLA-G in the pregnant woman and the fetus is partly derived from a "shared organ", the placenta....

[Pathogenesis of narcolepsy: from HLA association to hypocretin deficiency].

Science.gov (United States)

Klein, G; Burghaus, L; Diederich, N

2012-11-01

Narcolepsy is a rare and chronic sleep disorder, characterised by excessive daytime sleepiness. Frequently associated signs are cataplexy, sleep paralysis and hypnagogic or hypnopompic hallucinations. Advances in understanding the pathogenesis of the disease have essentially been elucidated during the last fifteen years. The most significant finding has been the discovery of hypocretin-1 and -2 in 1998. Hypocretin-containing cells have widespread projections throughout the entire CNS and play a crucial role in the regulation of the sleep-wake cycle. They also contribute to olefaction and to the regulation of food intake. Animal models and human studies concordantly show that the disturbed hypocretin system is the probable cause of narcolepsy. However, it remains unclear why there is neuronal death of hypocretin-producing cells in the lateral hypothalamus. As the HLA-allele DQB1*0602 is associated with narcolepsy and hypocretin deficiency, an autoimmune reaction against hypocretin-producing neurons has been vigorously discussed. Newly discovered gene polymorphisms as well as previously unknown pathogenetic mechanisms, linking the sleep-wake cycle with the immune system, may also contribute to the pathogenetic cascade. Worthy of mention in this context is, e.g., the "insulin-like growth factor"-binding protein 3 (IGFBP3), whose overexpression causes a down-regulation of the hypocretin production. Substitution of the deficient neuropeptides by hypocretin agonists may become the causal treatment strategy of the future, if an adequate administration route can be found. Presently, animal trials, including genetic therapy, cell transplantations or the administration of hypocretin receptor agonists, are underway. © Georg Thieme Verlag KG Stuttgart · New York.

Polimorfismo de los alelos de los antígenos de leucocitos humanos HLA-DRB1 y su asociación con la artritis reumatoidea juvenil en una muestra de niños mestizos colombianos.

Directory of Open Access Journals (Sweden)

Gloria Garavito

2003-09-01

Full Text Available Se buscó tipificar molecularmente los alelos de los antígenos de leucocitos humanos HLADRB1 en un grupo de niños mestizos colombianos (población resultante de la mezcla genética de amrindios, europeos y africanos con artritis reumatoidea juvenil (ARJ, así como analizar su frecuencia de expresión y compararla con sujetos clínicamente normales e investigar la asociación entre la frecuencia de los alelos con los diferentes subgrupos clínicos de ARJ. El estudio involucró 65 pacientes con ARJ y 65 controles sanos. La tipificación de los alelos HLADRB1 se realizó por medio de la metodología de la reacción en cadena de la polimerasa con sondas de oligonucleótidos de secuencias específicas (PCR-SSOP, utilizando el protocolo recomendado por el XII International Histocompatibilty Workshop, realizado en St. Malo, París, en 1996. Los alelos HLADRB1* 1104 (prueba exacta de Fisher, PEF=0,013, OR=16,79, frecuencia etiológica (FE=0,93 y DRB1*1602 (PEF=0,016, OR=8,98, FE=0,88 se evidenciaron como marcadores de susceptibilidad. HLA-DRB1*1501 (FP=0,466; p=0,005 y HLA DRB1*1402 (FP=0,49; p=0,009 se comportaron como alelos asociados con protección. Al comparar las asociaciones entre alelos y los diferentes subgrupos clínicos se encontró asociación entre ARJ oligoarticular con HLA-DRB1* 1104 (p=0,0034, OR=41,53 , FE=0,97, la ARJ poliarticular se asoció con el alelo HLADRB1* 0404 (p=0,012, OR=8,75, FE=0,88 y en el grupo sistémico, el alelo más expresado fue el HLA-DRB1*1602 (p=0,005, OR=21,33, FE=0,95. La presencia de factor reumatoide estuvo asociado con los alelos HLA-DRB1*0407 (p=0,05, OR=11,2, FE=0,45 y HLA-DRB1*1302 (p=0,02, OR=22,8, FE=0,63. En el grupo de pacientes con ANA+, sólo hubo significancia estadística para el alelo HLA-DRB1* 0701 (p=0,001, OR=58, FE=0,73. Nuestros resultados sugieren que los genes del MHC en este subgrupo étnico inciden no sólo en la susceptibilidad a desarrollar ARJ sino también en la expresión cl

Associations of HLA-A, HLA-B and HLA-C Alleles Frequency with Prevalence of Herpes Simplex Virus Infections and Diseases Across Global Populations: Implication for the Development of an Universal CD8+ T-Cell Epitope-Based Vaccine

Science.gov (United States)

Samandary, Sarah; Kridane-Miledi, Hédia; Sandoval, Jacqueline S.; Choudhury, Zareen; Langa-Vives, Francina; Spencer, Doran; Chentoufi, Aziz A.; Lemonnier, François A.; BenMohamed, Lbachir

2014-01-01

A significant portion of the world’s population is infected with herpes simplex virus type 1 and/or type 2 (HSV-1 and/or HSV-2), that cause a wide range of diseases including genital herpes, oro-facial herpes, and the potentially blinding ocular herpes. While the global prevalence and distribution of HSV-1 and HSV-2 infections cannot be exactly established, the general trends indicate that: (i) HSV-1 infections are much more prevalent globally than HSV-2; (ii) Over half billion people worldwide are infected with HSV-2; (iii) the sub-Saharan African populations account for a disproportionate burden of genital herpes infections and diseases; (iv) the dramatic differences in the prevalence of herpes infections between regions of the world appear to be associated with differences in the frequencies of human leukocyte antigen (HLA) alleles. The present report: (i) analyzes the prevalence of HSV-1 and HSV-2 infections across various regions of the world; (ii) analyzes potential associations of common HLA-A, HLA-B and HLA-C alleles with the prevalence of HSV-1 and HSV-2 infections in the Caucasoid, Oriental, Hispanic and Black major populations; and (iii) discusses how our recently developed HLA-A, HLA-B, and HLA-C transgenic/H-2 class I null mice will help validate HLA/herpes prevalence associations. Overall, high prevalence of herpes infection and disease appears to be associated with high frequency of HLA-A*24, HLA-B*27, HLA-B*53 and HLA-B*58 alleles. In contrast, low prevalence of herpes infection and disease appears to be associated with high frequency of HLA-B*44 allele. The finding will aid in developing a T-cell epitope-based universal herpes vaccine and immunotherapy. PMID:24798939

Effects of the genome on immune regulation in type 1 diabetes

DEFF Research Database (Denmark)

Pociot, Flemming; Kaur, Simranjeet; Nielsen, Lotte B

2016-01-01

Type 1 diabetes (T1DM) is a complex disease, arising through the interaction of an incompletely defined combination of genetic susceptibility and environmental factors. It is well accepted that T1DM results from selective immune-mediated destruction of the insulin-producing β cells in the islets...... CCL2 and CCL4 in recent onset T1DM patients. Finally, we report that genetic variants predict autoantibody positivity in T1DM cases....... into a limited number of DRB1 and DQB1 amino acid residues that account for most of the HLA-risk. Second, we use the Immunochip data to look for functional significance by correlation to circulating levels of chemokines and demonstrate that genetic variation at chromosome 2, 3, and 6 correlates with circulating...

HLA typing in acute optic neuritis

DEFF Research Database (Denmark)

Frederiksen, J L; Madsen, H O; Ryder, L P

1997-01-01

OBJECTIVE: To study the association of brain magnetic resonance imaging (MRI) findings and HLA findings to clarify the relationship between monosymptomatic optic neuritis (ON) and ON as part of clinically definite multiple sclerosis (CDMS). DESIGN: Population-based cohort of patients with ON refe......OBJECTIVE: To study the association of brain magnetic resonance imaging (MRI) findings and HLA findings to clarify the relationship between monosymptomatic optic neuritis (ON) and ON as part of clinically definite multiple sclerosis (CDMS). DESIGN: Population-based cohort of patients......: The frequency of HLA-DR15 was significantly increased in patients with ON + CDMS (52%) and ON (47%) compared with control subjects (31%). The frequency of HLA-DR17 was almost equal in the ON + CDMS (18%), ON (23%), and control (23%) groups. The frequencies of HLA-DQA-1B (55% in ON + CDMS, 58% in ON) and HLA...

Síndrome Poliglandular Autoinmune Tipo II: Posible Asociación con HLA DRB1*-DQB1* Possible association of Type II Autoimmune Polyendrocrine Syndrome with HLA DRB1*-DQB1*

OpenAIRE

M.S. Mallea Gil; M.C. Ballarino; M.M. Aparicio; K. Bertini; M.C. Ridruejo; S. Gimenez; P. Galarza; A. Perusco; S. Roveto; D. Rimoldi

2010-01-01

Los síndromes poliendocrinos autoinmunes (APS) asocian enfermedades endocrinas autoinmunes con otros desórdenes autoinmunes no endocrinos. El APS tipo II se caracteriza por compromiso primario suprarrenal, tiroideo y/o DM tipo I. Presentamos un paciente masculino de 46 años que fue internado por astenia, adinamia, hiporexia, severa disminución de peso, mareos y vómitos. Antecedente de obesidad y diabetes diagnosticada 3 años antes. Presentaba hipotensión arterial, hiperpigmentación de mucosas...

HLA-G allelic variants are associated with differences in the HLA-G mRNA isoform profile and HLA-G mRNA levels

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Hviid, Thomas Vauvert F; Hylenius, Sine; Rørbye, Christina

2003-01-01

between mother and fetus in several ways. Finally, the expression of membrane-bound HLA-G and soluble HLA-G has been proposed to influence the outcome of pregnancy, and an aberrant HLA-G expression in pre-eclamptic placentas and spontaneous abortions has been reported. Here, an association between certain...... HLA-G polymorphisms and the mRNA levels of the different alternatively spliced HLA-G isoforms in first trimester trophoblast cell populations is reported. Several alternatively spliced HLA-G mRNA isoforms, including a 14-bp polymorphism in the 3'UTR end (exon 8) of the HLA-G gene, are expressed...

Obesidad y factores de riesgo del síndrome metabólico en jóvenes con diabetes tipo 1 Obesity and risk factors for metabolic syndrome in young people with type 1 diabetes

Directory of Open Access Journals (Sweden)

Mariana Prieto

2012-08-01

Full Text Available Los cambios en la forma de presentación de la diabetes mellitus tipo 1(DM T1 en la infancia y adolescencia asociados a la obesidad, determinaron una superposición entre los dos tipos de diabetes, con mayor heterogeneidad en su presentación clínica. Con el objetivo de caracterizar el tipo de diabetes mellitus (DM, comienzo de la diabetes, independientemente de las clasificaciones disponibles y evaluar el impacto de la obesidad en la forma de presentación, se estudiaron cincuenta niños diabéticos agrupados según su condición nutricional. Se evaluó la reserva de insulina pancreática por medición de péptido C basal, índice glucemia/péptido C y en respuesta a comida mixta (MMTT, se determinó el genotipo HLA-DQB1 y los anticuerpos GADA, ICA 512, IAA y se evaluó la presencia de factores de riesgo para enfermedad metabólica como obesidad, hipertensión, diabetes y dislipidemia en el grupo familiar. El 38% de la población presentó sobrepeso/obesidad (SP/OB. Un 82% tuvo anticuerpos positivos GADA, ICA 512, IAA sin diferencia significativa entre ambos grupos, el 100% fue positivo para genotipo HLA-DQB1 de riesgo. El 84% de los familiares presentó factores de riesgo positivo para síndrome metabólico. Se dividió a la población en dos grupos (sobrepeso/obesidad vs. normopeso. No hubo diferencias en los valores de péptido C en ayunas o en el índice glucemia/péptido C entre los dos grupos El péptido C en el MMTT mostró mayor área bajo la curva (1.77 ng/ml vs. 5.5 ng/ml, p = 0.0007 y valores más altos a los 60 y 120 minutos (p: 0.02 y 0.03 en el grupo con SP/OB. En conclusión, los pacientes con diabetes tipo 1A con SP/OB tienen mayor capacidad de respuesta pancreática medida por péptido C, sugiriendo que el estado nutricional podría actuar como acelerador del comienzo clínico de la enfermedad.Changes in the clinical presentation of diabetes mellitus in childhood and adolescence associated with obesity have resulted in an

Conservation and diversity of influenza A H1N1 HLA-restricted T cell epitope candidates for epitope-based vaccines.

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Paul Thiamjoo Tan

2010-01-01

Full Text Available The immune-related evolution of influenza viruses is exceedingly complex and current vaccines against influenza must be reformulated for each influenza season because of the high degree of antigenic drift among circulating influenza strains. Delay in vaccine production is a serious problem in responding to a pandemic situation, such as that of the current H1N1 strain. Immune escape is generally attributed to reduced antibody recognition of the viral hemagglutinin and neuraminidase proteins whose rate of mutation is much greater than that of the internal non-structural proteins. As a possible alternative, vaccines directed at T cell epitope domains of internal influenza proteins, that are less susceptible to antigenic variation, have been investigated.HLA transgenic mouse strains expressing HLA class I A*0201, A*2402, and B*0702, and class II DRB1*1501, DRB1*0301 and DRB1*0401 were immunized with 196 influenza H1N1 peptides that contained residues of highly conserved proteome sequences of the human H1N1, H3N2, H1N2, H5N1, and avian influenza A strains. Fifty-four (54 peptides that elicited 63 HLA-restricted peptide-specific T cell epitope responses were identified by IFN-gamma ELISpot assay. The 54 peptides were compared to the 2007-2009 human H1N1 sequences for selection of sequences in the design of a new candidate H1N1 vaccine, specifically targeted to highly-conserved HLA-restricted T cell epitopes.Seventeen (17 T cell epitopes in PB1, PB2, and M1 were selected as vaccine targets based on sequence conservation over the past 30 years, high functional avidity, non-identity to human peptides, clustered localization, and promiscuity to multiple HLA alleles. These candidate vaccine antigen sequences may be applicable to any avian or human influenza A virus.

Analysis of Hypoxic and Hypercapnic Ventilatory Response in Healthy Volunteers

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Lin, Ling; Sharifi, Husham; Rico, Tom; Andlauer, Olivier; Aran, Adi; Bloomrosen, Efrat; Faraco, Juliette; Fang, Han; Mignot, Emmanuel

2017-01-01

Introduction A previous study has suggested that the Human Leukocyte Antigen (HLA) allele DQB1*06:02 affects hypoxic ventilatory response (HVR) but not hypercapnic ventilatory response (HCVR) in an Asian population. The current study evaluated the relationship in Caucasians and Asians. In addition we assessed whether gender or polymorphisms in genes participating in the control of breathing affect HVR and HCVR. Methods A re-breathing system was used to measure HVR and HCVR in 551 young adults (56.8% Caucasians, 30% Asians). HLA-DQB1*06:02 and tagged polymorphisms and coding variants in genes participating in breathing (PHOX2B, GPR4 and TASK2/KCNK5) were analyzed. The associations between HVR/HCVR and HLA-DQB1*06:02, genetic polymorphisms, and gender were evaluated using ANOVA or frequentist association testing with SNPTEST. Results HVR and gender are strongly correlated. HCVR and gender are not. Mean HVR in women was 0.276±0.168 (liter/minute/%SpO2) compared to 0.429±0.266 (liter/minute/%SpO2) in men, pHVR in men). Women had lower baseline minute ventilation (8.08±2.36 l/m vs. 10.00±3.43l/m, pHVR or HCVR. Genetic analysis revealed point wise, uncorrected significant associations between two TASK2/KCNK5 variants (rs2815118 and rs150380866) and HCVR. Conclusions This is the largest study to date reporting the relationship between gender and HVR/ HCVR and the first study assessing the association between genetic polymorphisms in humans and HVR/HCVR. The data suggest that gender has a large effect on hypoxic breathing response. PMID:28045995

Analysis of Hypoxic and Hypercapnic Ventilatory Response in Healthy Volunteers.

Science.gov (United States)

Goldberg, Shmuel; Ollila, Hanna Maria; Lin, Ling; Sharifi, Husham; Rico, Tom; Andlauer, Olivier; Aran, Adi; Bloomrosen, Efrat; Faraco, Juliette; Fang, Han; Mignot, Emmanuel

2017-01-01

A previous study has suggested that the Human Leukocyte Antigen (HLA) allele DQB1*06:02 affects hypoxic ventilatory response (HVR) but not hypercapnic ventilatory response (HCVR) in an Asian population. The current study evaluated the relationship in Caucasians and Asians. In addition we assessed whether gender or polymorphisms in genes participating in the control of breathing affect HVR and HCVR. A re-breathing system was used to measure HVR and HCVR in 551 young adults (56.8% Caucasians, 30% Asians). HLA-DQB1*06:02 and tagged polymorphisms and coding variants in genes participating in breathing (PHOX2B, GPR4 and TASK2/KCNK5) were analyzed. The associations between HVR/HCVR and HLA-DQB1*06:02, genetic polymorphisms, and gender were evaluated using ANOVA or frequentist association testing with SNPTEST. HVR and gender are strongly correlated. HCVR and gender are not. Mean HVR in women was 0.276±0.168 (liter/minute/%SpO2) compared to 0.429±0.266 (liter/minute/%SpO2) in men, pHVR in men). Women had lower baseline minute ventilation (8.08±2.36 l/m vs. 10.00±3.43l/m, pHVR or HCVR. Genetic analysis revealed point wise, uncorrected significant associations between two TASK2/KCNK5 variants (rs2815118 and rs150380866) and HCVR. This is the largest study to date reporting the relationship between gender and HVR/ HCVR and the first study assessing the association between genetic polymorphisms in humans and HVR/HCVR. The data suggest that gender has a large effect on hypoxic breathing response.

Clinicopathologic significance of HLA-G and HLA-E molecules in Tunisian patients with ovarian carcinoma.

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Babay, Wafa; Ben Yahia, Hamza; Boujelbene, Nadia; Zidi, Nour; Laaribi, Ahmed Baligh; Kacem, Dhikra; Ben Ghorbel, Radhia; Boudabous, Abdellatif; Ouzari, Hadda-Imene; Rizzo, Roberta; Rebmann, Vera; Mrad, Karima; Zidi, Inès

2018-06-01

The human leukocyte antigen (HLA)-G and HLA-E, non classical HLA class I molecules, have been highly implicated in immune tolerance. HLA-G and HLA-E molecules were proposed as putative markers of several advanced cancers. As a step towards a better understanding of ovarian carcinoma, we evaluated the expression of both HLA-G and HLA-E molecules and explored their prognostic implication. HLA-G and HLA-E expression were studied by immunohistochemistry on ovarian carcinoma tissues. This expression was semi-quantitatively scored into four expression groups and correlated to clinicopathological parameters and patients' survival. HLA-G and HLA-E have been found to be highly expressed in ovarian carcinoma tissues (Respectively, 72.4% and 96.8%). They are frequently co-expressed. Univariate and multivariate analysis revealed that a positive HLA-G expression status in tumor tissue is a promising candidate parameter to predict disease recurrence in addition to the disease status in Tunisian patients with ovarian carcinoma. Moreover, the elevated HLA-E expression was associated with serous ovarian carcinoma subtype as well as with advanced stages of ovarian carcinoma. HLA-G and HLA-E are highly represented in ovarian carcinoma suggesting a potential association with progressive disease mechanism. HLA-G and HLA-E molecules might be new candidates' markers for ovarian carcinoma progression. Copyright © 2018 American Society for Histocompatibility and Immunogenetics. Published by Elsevier Inc. All rights reserved.

Moving Beyond HLA: A Review of nHLA Antibodies in Organ Transplantation

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Sigdel, Tara K.; Sarwal, Minnie M.

2013-01-01

Given the finite graft life expectancy of HLA identical organ transplants and the recognition of humoral graft injury in the absence of donor directed anti-HLA antibodies, the clinical impact of antibodies against non-HLA (nHLA) antigens in transplant injury is being increasingly recognized. The recognition of the impact of nHLA antigen discrepancies between donor and recipient on transplant outcomes is timely given the advances in rapid and lower cost sequencing methods that can soon provide...

HLA-B*39:06 Efficiently Mediates Type 1 Diabetes in a Mouse Model Incorporating Reduced Thymic Insulin Expression.

Science.gov (United States)

Schloss, Jennifer; Ali, Riyasat; Racine, Jeremy J; Chapman, Harold D; Serreze, David V; DiLorenzo, Teresa P

2018-04-09

Type 1 diabetes (T1D) is characterized by T cell-mediated destruction of the insulin-producing β cells of the pancreatic islets. Among the loci associated with T1D risk, those most predisposing are found in the MHC region. HLA-B*39:06 is the most predisposing class I MHC allele and is associated with an early age of onset. To establish an NOD mouse model for the study of HLA-B*39:06, we expressed it in the absence of murine class I MHC. HLA-B*39:06 was able to mediate the development of CD8 T cells, support lymphocytic infiltration of the islets, and confer T1D susceptibility. Because reduced thymic insulin expression is associated with impaired immunological tolerance to insulin and increased T1D risk in patients, we incorporated this in our model as well, finding that HLA-B*39:06-transgenic NOD mice with reduced thymic insulin expression have an earlier age of disease onset and a higher overall prevalence as compared with littermates with typical thymic insulin expression. This was despite virtually indistinguishable blood insulin levels, T cell subset percentages, and TCR Vβ family usage, confirming that reduced thymic insulin expression does not impact T cell development on a global scale. Rather, it will facilitate the thymic escape of insulin-reactive HLA-B*39:06-restricted T cells, which participate in β cell destruction. We also found that in mice expressing either HLA-B*39:06 or HLA-A*02:01 in the absence of murine class I MHC, HLA transgene identity alters TCR Vβ usage by CD8 T cells, demonstrating that some TCR Vβ families have a preference for particular class I MHC alleles. Copyright © 2018 by The American Association of Immunologists, Inc.

HLA-A*7401-mediated control of HIV viremia is independent of its linkage disequilibrium with HLA-B*5703

DEFF Research Database (Denmark)

Matthews, Philippa C; Adland, Emily; Listgarten, Jennifer

2011-01-01

-clade-infected subjects. We present evidence that HLA-A*7401 operates an effect that is independent of HLA-B*5703, with which it is in linkage disequilibrium in some populations, to mediate lowered viremia. We describe a novel statistical approach to detecting additive effects between class I alleles in control of HIV-1...... epitopes appear immunodominant. We identify eight novel putative HLA-A*7401-restricted epitopes, of which three have been defined to the optimal epitope. In common with HLA-B alleles linked with slow progression, viremic control through an HLA-A*7401-restricted response appears to be associated...... with the selection of escape mutants within Gag epitopes that reduce viral replicative capacity. These studies highlight the potentially important contribution of an HLA-A allele to immune control of HIV infection, which may have been concealed by a stronger effect mediated by an HLA-B allele with which...

Can Non-HLA Single Nucleotide Polymorphisms Help Stratify Risk in TrialNet Relatives at Risk for Type 1 Diabetes?

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Steck, Andrea K; Xu, Ping; Geyer, Susan; Redondo, Maria J; Antinozzi, Peter; Wentworth, John M; Sosenko, Jay; Onengut-Gumuscu, Suna; Chen, Wei-Min; Rich, Stephen S; Pugliese, Alberto

2017-08-01

Genome-wide association studies identified >50 type 1 diabetes (T1D) associated non-human leukocyte antigens (non-HLA) loci. The purpose of this study was to assess the contribution of non-HLA single nucleotide polymorphisms (SNPs) to risk of disease progression. The TrialNet Pathway to Prevention Study follows relatives of T1D patients for development of autoantibodies (Abs) and T1D. Using the Immunochip, we analyzed 53 diabetes-associated, non-HLA SNPs in 1016 Ab-positive, at-risk non-Hispanic white relatives. Effect of SNPs on the development of multiple Abs and T1D. Cox proportional analyses included all substantial non-HLA SNPs, HLA genotypes, relationship to proband, sex, age at initial screening, initial Ab type, and number. Factors involved in progression from single to multiple Abs included age at screening, relationship to proband, HLA genotypes, and rs3087243 (cytotoxic T lymphocyte antigen-4). Significant factors for diabetes progression included age at screening, Ab number, HLA genotypes, rs6476839 [GLIS family zinc finger 3 (GLIS3)], and rs3184504 [SH2B adaptor protein 3 (SH2B3)]. When glucose area under the curve (AUC) was included, factors involved in disease progression included glucose AUC, age at screening, Ab number, relationship to proband, HLA genotypes, rs6476839 (GLIS3), and rs7221109 (CCR7). In stratified analyses by age, glucose AUC, age at screening, sibling, HLA genotypes, rs6476839 (GLIS3), and rs4900384 (C14orf64) were significantly associated with progression to diabetes in participants <12 years old, whereas glucose AUC, sibling, rs3184504 (SH2B3), and rs4900384 (C14orf64) were significant in those ≥12. In conclusion, we identified five non-HLA SNPs associated with increased risk of progression from Ab positivity to disease that may improve risk stratification for prevention trials. Copyright © 2017 by the Endocrine Society

HLA-DRB1 alleles in four Amerindian populations from Argentina and Paraguay

Science.gov (United States)

2009-01-01

The major histocompatibility complex (MHC) is one of the biological systems of major polymorphisms. The study of HLA class II variability has allowed the identification of several alleles that are characteristic to Amerindian populations, and it is an excellent tool to define the relations and biological affinities among them. In this work, we analyzed the allelic distribution of the HLA-DRB1 class II locus in four Amerindian populations: Mapuche (n = 34) and Tehuelche (n = 23) from the Patagonian region of Argentina, and Wichi SV (n = 24) and Lengua (n = 17) from the Argentinean and Paraguayan Chaco regions, respectively. In all of these groups, relatively high frequencies of Amerindian HLA-DRB1 alleles were observed (DRB1*0403, DRB1*0407, DRB1*0411, DRB1*0417, DRB1*0802, DRB1*0901, DRB1*1402, DRB1*1406 and DRB1*1602). However, we also detected the presence of non-Amerindian variants in Mapuche (35%) and Tehuelche (22%). We compared our data with those obtained in six indigenous groups of the Argentinean Chaco region and in a sample from Buenos Aires City. The genetic distance dendrogram showed a clear-cut division between the Patagonian and Chaco populations, which formed two different clusters. In spite of their linguistic differences, it can be inferred that the biological affinities observed are in concordance with the geographic distributions and interethnic relations established among the groups studied. PMID:21637670

Genome-wide meta-analysis associates HLA-DQA1/DRB1 and LPA and lifestyle factors with human longevity

DEFF Research Database (Denmark)

Joshi, Peter K; Pirastu, Nicola; Kentistou, Katherine A

2017-01-01

Genomic analysis of longevity offers the potential to illuminate the biology of human aging. Here, using genome-wide association meta-analysis of 606,059 parents' survival, we discover two regions associated with longevity (HLA-DQA1/DRB1 and LPA). We also validate previous suggestions that APOE...... that an increase of one body mass index unit reduces lifespan by 7 months while 1 year of education adds 11 months to expected lifespan.Variability in human longevity is genetically influenced. Using genetic data of parental lifespan, the authors identify associations at HLA-DQA/DRB1 and LPA and find that genetic...

High level of soluble HLA-G in the female genital tract of Beninese commercial sex workers is associated with HIV-1 infection.

Science.gov (United States)

Thibodeau, Valérie; Lajoie, Julie; Labbé, Annie-Claude; Zannou, Marcel D; Fowke, Keith R; Alary, Michel; Poudrier, Johanne; Roger, Michel

2011-01-01

Most HIV infections are transmitted across mucosal epithelium. Understanding the role of innate and specific mucosal immunity in susceptibility or protection against HIV infection, as well as the effect of HIV infection on mucosal immunity, are of fundamental importance. HLA-G is a powerful modulator of the immune response. The aim of this study was to investigate whether soluble HLA-G (sHLA-G) expression in the female genital tract is associated with HIV-1 infection. Genital levels of sHLA-G were determined in 52 HIV-1-uninfected and 44 antiretroviral naïve HIV-1-infected female commercial sex workers (CSWs), as well as 71 HIV-1-uninfected non-CSW women at low risk of exposure, recruited in Cotonou, Benin. HIV-1-infected CSWs had higher genital levels of sHLA-G compared with those in both the HIV-1-uninfected CSW (P = 0.009) and non-CSW groups (P = 0.0006). The presence of bacterial vaginosis (P = 0.008), and HLA-G*01:01:02 genotype (P = 0.002) were associated with higher genital levels of sHLA-G in the HIV-1-infected CSWs, whereas the HLA-G*01:04:04 genotype was also associated with higher genital level of sHLA-G in the overall population (P = 0.038). When adjustment was made for all significant variables, the increased expression of sHLA-G in the genital mucosa remained significantly associated with both HIV-1 infection (P = 0.02) and bacterial vaginosis (P = 0.03). This study demonstrates that high level of sHLA-G in the genital mucosa is independently associated with both HIV-1 infection and bacterial vaginosis.

Strategy for monitoring T cell responses to NY-ESO-1 in patients with any HLA class I allele

Science.gov (United States)

Gnjatic, Sacha; Nagata, Yasuhiro; Jäger, Elke; Stockert, Elisabeth; Shankara, Srinivas; Roberts, Bruce L.; Mazzara, Gail P.; Lee, Sang Yull; Dunbar, P. Rod; Dupont, Bo; Cerundolo, Vincenzo; Ritter, Gerd; Chen, Yao-Tseng; Knuth, Alexander; Old, Lloyd J.

2000-01-01

NY-ESO-1 elicits frequent antibody responses in cancer patients, accompanied by strong CD8+ T cell responses against HLA-A2-restricted epitopes. To broaden the range of cancer patients who can be assessed for immunity to NY-ESO-1, a general method was devised to detect T cell reactivity independent of prior characterization of epitopes. A recombinant adenoviral vector encoding the full cDNA sequence of NY-ESO-1 was used to transduce CD8-depleted peripheral blood lymphocytes as antigen-presenting cells. These modified antigen-presenting cells were then used to restimulate memory effector cells against NY-ESO-1 from the peripheral blood of cancer patients. Specific CD8+ T cells thus sensitized were assayed on autologous B cell targets infected with a recombinant vaccinia virus encoding NY-ESO-1. Strong polyclonal responses were observed against NY-ESO-1 in antibody-positive patients, regardless of their HLA profile. Because the vectors do not cross-react immunologically, only responses to NY-ESO-1 were detected. The approach described here allows monitoring of CD8+ T cell responses to NY-ESO-1 in the context of various HLA alleles and has led to the definition of NY-ESO-1 peptides presented by HLA-Cw3 and HLA-Cw6 molecules. PMID:11005863

Predictors of hypocretin (orexin) deficiency in narcolepsy without cataplexy.

Science.gov (United States)

Andlauer, Olivier; Moore, Hyatt; Hong, Seung-Chul; Dauvilliers, Yves; Kanbayashi, Takashi; Nishino, Seiji; Han, Fang; Silber, Michael H; Rico, Tom; Einen, Mali; Kornum, Birgitte R; Jennum, Poul; Knudsen, Stine; Nevsimalova, Sona; Poli, Francesca; Plazzi, Giuseppe; Mignot, Emmanuel

2012-09-01

To compare clinical, electrophysiologic, and biologic data in narcolepsy without cataplexy with low (≤ 110 pg/ml), intermediate (110-200 pg/ml), and normal (> 200 pg/ml) concentrations of cerebrospinal fluid (CSF) hypocretin-1. University-based sleep clinics and laboratories. Narcolepsy without cataplexy (n = 171) and control patients (n = 170), all with available CSF hypocretin-1. Retrospective comparison and receiver operating characteristics curve analysis. Patients were also recontacted to evaluate if they developed cataplexy by survival curve analysis. The optimal cutoff of CSF hypocretin-1 for narcolepsy without cataplexy diagnosis was 200 pg/ml rather than 110 pg/ml (sensitivity 33%, specificity 99%). Forty-one patients (24%), all HLA DQB1*06:02 positive, had low concentrations (≤ 110 pg/ml) of CSF hypocretin-1. Patients with low concentrations of hypocretin-1 only differed subjectively from other groups by a higher Epworth Sleepiness Scale score and more frequent sleep paralysis. Compared with patients with normal hypocretin-1 concentration (n = 117, 68%), those with low hypocretin-1 concentration had higher HLA DQB1*06:02 frequencies, were more frequently non-Caucasians (notably African Americans), with lower age of onset, and longer duration of illness. They also had more frequently short rapid-eye movement (REM) sleep latency (≤ 15 min) during polysomnography (64% versus 23%), and shorter sleep latencies (2.7 ± 0.3 versus 4.4 ± 0.2 min) and more sleep-onset REM periods (3.6 ± 0.1 versus 2.9 ± 0.1 min) during the Multiple Sleep Latency Test (MSLT). Patients with intermediate concentrations of CSF hypocretin-1 (n = 13, 8%) had intermediate HLA DQB1*06:02 and polysomnography results, suggesting heterogeneity. Of the 127 patients we were able to recontact, survival analysis showed that almost half (48%) with low concentration of CSF hypocretin-1 had developed typical cataplexy at 26 yr after onset, whereas only 2% had done so when CSF hypocretin-1

HLA-DQ genetic risk gradient for type 1 diabetes and celiac disease in north-western Mexico

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M.E. Mejía-León

2015-04-01

Conclusion: The Sonoran population has a distinctive HLA-DQ allele distribution due to its ancestry. The HLA-DQ8 combinations with DQ2 or one of its alleles conferred the highest risk for both diseases and T1D and CD frequently appear together.