WorldWideScience

Sample records for hla class iii

  1. HLA class II haplotypes differentiate between the adult autoimmune polyglandular syndrome types II and III.

    Science.gov (United States)

    Flesch, B K; Matheis, N; Alt, T; Weinstock, C; Bux, J; Kahaly, G J

    2014-01-01

    Genetics of the adult autoimmune polyglandular syndrome (APS) is poorly understood. The aim of this study was to gain further insight into the genetics of the adult APS types. SITE: The study was conducted at a university referral center. The human leukocyte antigen (HLA) class II alleles, haplotypes, and genotypes were determined in a large cohort of patients with APS, autoimmune thyroid disease (AITD), and type 1 diabetes and in healthy controls by the consistent application of high-resolution typing at a four-digit level. Comparison of the allele and haplotype frequencies significantly discriminated patients with APS vs AITD and controls. The HLA class II alleles DRB1*03:01 *04:01, DQA1*03:01, *05:01, DQB1*02:01, and *03:02 were observed more frequently (Pdisease (APS type II) and those without Addison's disease but including type 1 diabetes and AITD (APS type III) demonstrated DR3-DQ2/DRB1*04:01-DQ8 as a susceptibility genotype in APS III (Pctype II (Pctypes II and III. Susceptible haplotypes favor the development of polyglandular autoimmunity in patients with AITD.

  2. Association of single-nucleotide polymorphisms in HLA class II/III region with knee osteoarthritis.

    Science.gov (United States)

    Shi, D; Zheng, Q; Chen, D; Zhu, L; Qin, A; Fan, J; Liao, J; Xu, Z; Lin, Z; Norman, P; Xu, J; Nakamura, T; Dai, K; Zheng, M; Jiang, Q

    2010-11-01

    A genome-wide association study and a replication using Japanese, Spanish and Greek Caucasian populations have recently indicated two single-nucleotide polymorphisms (SNPs) (rs7775228 and rs10947262) associated with knee Osteoarthritis (OA) susceptibility. We have further evaluated the association in knee OA subjects from Han Chinese and Australian Caucasian origin. Two independent case-control association studies were performed using Han Chinese and Australian Caucasian populations. The two SNPs were genotyped in patients who had primary symptomatic knee OA with radiographic confirmation and/or received total knee replacement surgery as well as in matched controls. They were subjected to statistic analyses. A total of 991 OA patients and 1536 controls were genotyped. No significant difference was detected in genotype or allele frequencies of the two SNPs between knee OA and control groups in the two populations (all P>0.05). The association was also negative even after stratification by sex, body mass index (BMI) and Kellgren/Lawrence scores. The significant heterogeneity was detected between Chinese and Japanese (both P0.05). The result of meta-analysis showed significant association between knee OA and rs10947262 in total subjects [summary OR=1.26, 95%confidence intervals (CI)=1.07-1.27, P=3 × 10(-8)] and in Caucasian samples (summary OR=1.28, 95%CI=1.04-1.57, P=0.02). We demonstrated no association between the two SNPs in human leukocyte antigen (HLA) class II/III region and knee OA in Han Chinese population. A significant association was detected between SNP rs10947262 and knee OA in Caucasian subjects. Further replication studies are required to identify the impact of controversial association. Copyright © 2010 Osteoarthritis Research Society International. All rights reserved.

  3. No increased susceptibility to breast cancer from combined CHEK2 1100delC genotype and the HLA class III region risk factors

    NARCIS (Netherlands)

    de Jong, Mirjam; Nolte, Ilja; te Meerman, Gerhardus; van der Graaf, WTA; Oosterom, E; Bruinenberg, M; van der Steege, G; Oosterwijk, JC; van der Hout, Annemarie; Boezen, HM; Schaapveld, M; Kleibeuker, JH; de Vries, EGE

    CHEK2 is low-penetrance breast cancer susceptibility gene. The 1100delC mutation may interact with variants/mutations in other breast cancer susceptibility loci. We identified a risk haplotype in the HLA class III region in breast cancer patients [de Jong MM, Nolte IM, de Vries EGE, et al. The HLA

  4. The HLA class III subregion is responsible for an increased breast cancer risk

    NARCIS (Netherlands)

    de Jong, Mirjam; Nolte, IM; de Vries, EGE; Schaapveld, M; Kleibeuker, JH; Oosterom, E; Oosterwijk, JC; van der Hout, Annemarie; van der Steege, G; Bruinenberg, M; Boezen, HM; te Meerman, Gerhardus; van der Graaf, WTA

    2003-01-01

    BRCA1 and BRCA2 germline mutations account for <5% of breast cancer cases. Less penetrant breast cancer susceptibility genes are likely to exist. Earlier studies have suggested involvement of the HLA region. The HLA region was genotyped with 24 microsatellite markers and markers for two single

  5. The Possible Involvement of HLA Class III Haplotype (RAGE, HSP70 and TNF Genes) in Alzheimer's Disease.

    Science.gov (United States)

    Boiocchi, Chiara; Maggioli, Elisa; Monti, Maria Cristina; Zorzetto, Michele; Sinforiani, Elena; Cereda, Cristina; Ricevuti, Giovanni; Cuccia, Mariaclara

    2015-01-01

    In the central nervous system Hsp70s seems to have a protective role in repair and removal of cellular proteins damaged by stress conditions. A protective role of Hsp70 was also shown in Alzheimer Disease. The HSP70-1 +190 G/C polymorphism is located in the gene 5'UTR region and it is implicated in alteration of the transcription binding factor; HSP70-2 +1267 A/G causes a silent mutation in the coding region and it seems to influence the mechanism of mRNA translation; HSP70-hom +2437 A/G causes a substitution Met → The (M493T) in the coding region and it seems to influence the bond with the substrate and therefore on the chaperone activity of hsp70. The aim of our study will be to investigate Alzheimer susceptibility to Hsp70 polymorphisms, taking into account our previous findings on HLA class III region, and to hypothesize a role of HLA class III haplotype configuration based on the variants of three genes: RAGE, HSP70 and TNF. We studied these polymorphisms with PCR-RFLP and PCR-TSP. We investigated 173 AD patients and 211 control subjects. Our results have shown a statistically significant decrease of the C allele frequency of the HSP70-1 +190 G/C polymorphism in AD patients vs controls (P value = 0,018), as well as the G allele of HSP70-2 +1267 G/A (p value = 0,02). We focalized our attention on haplotype reconstruction. We have observed a significant statistically decrease of GGT haplotype frequency (empirical p-value=0.0133 ); GAT haplotype was statistically significant increase in AD patients compared with control (empirical p-value=0.007). The total HLA class III haplotype are reconstructed. The causative haplotypes are the following ones: TTGATGGG ( p value =0,005; empirical p =0,0042); TTGATAGG (p value =0,45; empirical p =0,034). Patients with these haplotypes may show an earlier onset of the disease than patients with TTGGTGGG (p value=0,0138; empirical p =0,0102); TTCGTGGG (p value=0,021; empirical p =0,017); TTCGTGGA (p value =0,058; empirical p =0

  6. Genetic analysis of multicase families of visceral leishmaniasis in northeastern Brazil: no major role for class II or class III regions of HLA.

    Science.gov (United States)

    Peacock, C S; Sanjeevi, C B; Shaw, M-A; Collins, A; Campbell, R D; March, R; Silveira, F; Costa, J; Coste, C H; Nascimento, M D; Siddiqui, R; Shaw, J J; Blackwell, J M

    2002-09-01

    Familial aggregation, high relative risk to siblings, and segregation analysis, suggest genetic control of visceral leishmaniasis in Brazil. Class II gene effects in mice, and high circulating tumour necrosis factor alpha in humans, provide reasons to target HLA. Fifteen polymorphic markers across 1.03 Mb (DQB1 to TNFa) were genotyped (87 multicase families; 638 individuals). Model-based parametric analyses using single-point combined segregation and linkage in COMDS, or multi-point linkage in ALLEGRO, failed to detect linkage. Model-free nonparametric affected sibling pair (SPLINK) or NPL(all) score (ALLEGRO) analyses also failed to detect linkage. Information content mapping confirmed sufficient marker information to detect linkage. Analysis of simulated data sets demonstrated that these families had 100% power to detect NPL(all) scores of 5 to 6 (>LOD4; P age-related penetrances for a disease susceptibility gene. The extended transmission disequilibrium test (TDT) showed no consistent allelic associations between disease and the 15 loci. TDT also failed to detect significant associations between extended haplotypes and disease, consistent with failure to detect significant linkage disequilibrium across the region. Linkage disequilibrium between adjacent groups of markers (HLADQ/DR; 82-1/82-3/-238bpTNFA; LTA/62/TNFa) was not accompanied by significant global haplotype TDT associations with disease. The data suggest that class II/III regions of HLA do not contain major disease gene(s) for visceral leishmaniasis in Brazil.

  7. Association with HLA class I in Epstein-Barr-virus-positive and with HLA class III in Epstein-Barr-virus-negative Hodgkin's lymphoma

    NARCIS (Netherlands)

    Diepstra, A; Niens, M; Vellenga, E; van Imhoff, GW; Nolte, IM; Schaapveld, M; van der Steege, G; van den Berg, Anke; Kibbelaar, RE; te Meerman, GJ; Poppema, S

    2005-01-01

    Background Associations of Hodgkin's lymphoma with HLA have been reported for many years. In 20-40% of patients with this disorder, Epstein-Barr virus (EBV) is present in the neoplastic cells. Because presentation of EBV antigenic peptides can elicit vigorous immune responses, we investigated

  8. Association of HLA-A and Non-Classical HLA Class I Alleles

    Science.gov (United States)

    Carlini, Federico; Ferreira, Virginia; Buhler, Stéphane; Tous, Audrey; Eliaou, Jean-François; René, Céline; Chiaroni, Jacques; Picard, Christophe; Di Cristofaro, Julie

    2016-01-01

    The HLA-A locus is surrounded by HLA class Ib genes: HLA-E, HLA-H, HLA-G and HLA-F. HLA class Ib molecules are involved in immuno-modulation with a central role for HLA-G and HLA-E, an emerging role for HLA-F and a yet unknown function for HLA-H. Thus, the principal objective of this study was to describe the main allelic associations between HLA-A and HLA-H, -G, -F and -E. Therefore, HLA-A, -E, -G, -H and -F coding polymorphisms, as well as HLA-G UnTranslated Region haplotypes (referred to as HLA-G UTRs), were explored in 191 voluntary blood donors. Allelic frequencies, Global Linkage Disequilibrium (GLD), Linkage Disequilibrium (LD) for specific pairs of alleles and two-loci haplotype frequencies were estimated. We showed that HLA-A, HLA-H, HLA-F, HLA-G and HLA-G UTRs were all in highly significant pairwise GLD, in contrast to HLA-E. Moreover, HLA-A displayed restricted associations with HLA-G UTR and HLA-H. We also confirmed several associations that were previously found to have a negative impact on transplantation outcome. In summary, our results suggest complex functional and clinical implications of the HLA-A genetic region. PMID:27701438

  9. Association of HLA-A and Non-Classical HLA Class I Alleles

    OpenAIRE

    Carlini, Federico; Ferreira, Virginia; Buhler, St?phane; Tous, Audrey; Eliaou, Jean-Fran?ois; Ren?, C?line; Chiaroni, Jacques; Picard, Christophe; Di Cristofaro, Julie

    2016-01-01

    The HLA-A locus is surrounded by HLA class Ib genes: HLA-E, HLA-H, HLA-G and HLA-F. HLA class Ib molecules are involved in immuno-modulation with a central role for HLA-G and HLA-E, an emerging role for HLA-F and a yet unknown function for HLA-H. Thus, the principal objective of this study was to describe the main allelic associations between HLA-A and HLA-H, -G, -F and -E. Therefore, HLA-A, -E, -G, -H and -F coding polymorphisms, as well as HLA-G UnTranslated Region haplotypes (referred to a...

  10. Short tandem repeat (STR) haplotypes in HLA: an integrated 50-kb STR/linkage disequilibrium/gene map between the RING3 and HLA-B genes and identification of STR haplotype diversification in the class III region.

    Science.gov (United States)

    Vorechovsky, I; Kralovicova, J; Laycock, M D; Webster, A D; Marsh, S G; Madrigal, A; Hammarström, L

    2001-08-01

    We present a dense STR/linkage disequilibrium(LD)/gene map between the RING3 and HLA-B loci, reference allelic sizes on the most prevalent HLA haplotypes and their allelic frequencies in pedigree founders. This resource will facilitate LD, evolution and gene mapping studies, including comparisons of HLA and STR haplotypes and identification of HLA recombinants. The map was constructed by testing novel and previously reported STRs using a panel of 885 individuals in 211 families and 60 DNA samples from cell lines and bone marrow donors homozygous in the HLA-A, -B and -DR loci selected from over 15 000 entries into the registry of Swedish bone marrow donors. We have also analysed the variability of STR alleles/haplotypes on the most prevalent HLA haplotypes to identify STRs useful for fine mapping of disease genes in the region previously implicated in susceptibility to many disorders. The analysis of 40 HLA-A*01, B*0801, DRB1*03011, DQB1*0201 haplotypes in homozygous donors showed a surprising stability in 23 STRs between the class II recombination hot spot and HLA-B, with the average of 1.9% (16/838) variant alleles. However, 40% variant alleles were found at the D6S2670 locus in intron 19 of the tenascin-X gene both in the families and homozygous donors. The nucleotide sequence analysis of this STR showed a complex polymorphism consisting of tetra- (CTTT)(8-18) and penta-nucleotide (CTTTT)(1-2) repeats, separated by an intervening non-polymorphic sequence of 42 bp. The HLA-A1, B*0801, DRB1*03011, DQB1*0201 haplotypes had five (CTTT)(14-18)/(CTTTT)(2) variants with a predominant (CTTT)(16) allele, implicating the tetranucleotide component as the source of this ancestral haplotype diversification, which may be due to the location of D6S2670 in the region of the highest GC content in the human MHC.

  11. Class II HLA interactions modulate genetic risk for multiple sclerosis

    Science.gov (United States)

    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

  12. Class II HLA interactions modulate genetic risk for multiple sclerosis

    DEFF Research Database (Denmark)

    Moutsianas, Loukas; Jostins, Luke; Beecham, Ashley H

    2015-01-01

    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...

  13. HLA class Ib in pregnancy and pregnancy-related disorders.

    Science.gov (United States)

    Persson, Gry; Melsted, Wenna Nascimento; Nilsson, Line Lynge; Hviid, Thomas Vauvert F

    2017-08-01

    The HLA class Ib genes, HLA-E, HLA-F, and HLA-G, were discovered long after the classical HLA class Ia genes. The elucidation of their functions had a modest beginning. However, their basic functions and involvement in pathophysiology and a range of diseases are now emerging. Although results from a range of studies support the functional roles for the HLA class Ib molecules in adult life, especially HLA-G and HLA-F have most intensively been, and were also primarily, studied in relation to reproduction and pregnancy. The expression of HLA class Ib proteins at the feto-maternal interface in the placenta seems to be important for the maternal acceptance of the semi-allogenic fetus. In contrast to the functions of HLA class Ia, HLA-G possesses immune-modulatory and tolerogenic functions. Here, we review an accumulating amount of data describing the functions of HLA class Ib molecules in relation to fertility, reproduction, and pregnancy, and a possible role for these molecules in certain pregnancy complications, such as implantation failure, recurrent spontaneous abortions, and pre-eclampsia. The results from different kinds of studies point toward a role for HLA class Ib, especially HLA-G, throughout the reproductive cycle from conception to the birth weight of the child.

  14. HLA class Ib in pregnancy and pregnancy-related disorders

    DEFF Research Database (Denmark)

    Persson, Gry; Melsted, Wenna Nascimento; Nilsson, Line Lynge

    2017-01-01

    a range of studies support the functional roles for the HLA class Ib molecules in adult life, especially HLA-G and HLA-F have most intensively been, and were also primarily, studied in relation to reproduction and pregnancy. The expression of HLA class Ib proteins at the feto-maternal interface...... to fertility, reproduction, and pregnancy, and a possible role for these molecules in certain pregnancy complications, such as implantation failure, recurrent spontaneous abortions, and pre-eclampsia. The results from different kinds of studies point toward a role for HLA class Ib, especially HLA-G, throughout...

  15. Expression of HLA Class I and HLA Class II by Tumor Cells in Chinese Classical Hodgkin Lymphoma Patients

    NARCIS (Netherlands)

    Huang, Xin; van den Berg, Anke; Gao, Zifen; Visser, Lydia; Nolte, Ilja; Vos, Hans; Hepkema, Bouke; Kooistra, Wierd; Poppema, Sibrand; Diepstra, Arjan

    2010-01-01

    Background: In Caucasian populations, the tumor cells of Epstein Barr virus (EBV)-positive classical Hodgkin Lymphomas (cHL) patients more frequently express HLA class I and HLA class II molecules compared to EBV-negative cHL patients. HLA expression (in relation to EBV) in Asian cHL patients has

  16. HLA class I and class II HLA DRB profiles in Egyptian children with rheumatic valvular disease.

    Science.gov (United States)

    El-Hagrassy, Nashwa; El-Chennawi, Farha; Zaki, Maysaa El-Sayed; Fawzy, Hossam; Zaki, Adel; Joseph, Nabeil

    2010-07-01

    Poststreptococcal sequelae, especially acute rheumatic fever/rheumatic heart disease continues to occur in significant proportions in many parts of the world, especially in less developed countries. An important factor in the study of rheumatic heart disease is the human genetic susceptibility to the disease. The aim of the present study was to detect the most prevalent HLA class I and class II types associated with risk of rheumatic heart disease in Egyptian children. Our study was performed on 100 patients with rheumatic valvular heart diseases and 71 control subjects. Patients were recruited from the Heart Institute, Embaba, Egypt. HLA typing for HLA class I was performed by serotyping and HLDR allele genotyping was performed using INNO-LiPA kits. In the study of HLA class I, there was a statistically significant increase in the B5 allele (P = 0.03; odds ratio, 3.46 [1.12-10.72]) in patients compared to controls, while B49 and B52 alleles (P = 0.004 and P = 0.02) were found in controls only. There was a statistically significant increase in HLA DR* 04-02, 3.46 (1.12-10.72) and HLA DR *10-0101 5.75 (1.27-25.98) in patients. Meanwhile HLA DR*1309120 was found only in controls (P = 0.02). Our study provides further information on the genetic predisposition for rheumatic valvular disease and the protective genotypes in rheumatic heart disease. Further insight into the molecular mechanisms of the disease will be a useful tool for predicting clinical outcome in those patients and, thus, potentially offer new means and approaches to treatment and prophylaxis, including a potential vaccine.

  17. Short tandem repeat (STR) haplotypes in HLA: an integrated 50-kb STR/linkage disequilibrium/gene map between the RING3 and HLA-B genes and identification of STR haplotype diversification in the class III region

    National Research Council Canada - National Science Library

    Vorechovsky, I; Kralovicova, J; Laycock, M D; Webster, A D; Marsh, S G; Madrigal, A; Hammarström, L

    2001-01-01

    We present a dense STR/linkage disequilibrium(LD)/gene map between the RING3 and HLA-B loci, reference allelic sizes on the most prevalent HLA haplotypes and their allelic frequencies in pedigree founders...

  18. Pseudo Class III malocclusion

    National Research Council Canada - National Science Library

    Al-Hummayani, Fadia M

    2016-01-01

    .... This case report represents a none traditional treatment modality to treat deep anterior crossbite in an adult pseudo class III malocclusion complicated by severely retruded, supraerupted upper and lower incisors...

  19. Antigens HLA-G, sHLA- G and sHLA- class I in reproductive failure.

    Directory of Open Access Journals (Sweden)

    Elzbieta Ronin-Walknowska

    2008-04-01

    Full Text Available It can be supposed that relation between HLA-G polymorphism and sHLA-G protein expression are associated with successful embryo implantation and pregnancy maintenance. The aim of the study was the estimation specific differences in expression of sHLA-G and sHLA- class I antigens in women with reproductive failure in comparison with fertile women. The study sample enrolled 80 women, divided into 2 groups. The study group (B enrolled 60 women with reproductive failure including 20 women with 3 recurrent spontaneous abortions in the first trimester of pregnancy (RSA, 20 women with empty sac (ES and 20 women with 3 consecutive in-vitro fertilization failures (IVFf. The control group (C enrolled 20 fertile women with at least 2 children. Soluble HLA- class I antigens (sHLA-I and soluble HLA-G (sHLA-G were determined using ELISA test kits from IBio Vendor Labolatory Medicine, Inc. HLA-G allele found in individuals in our study were identified by comparing the obtained bp sequences of exon 2., 3. and 4. with bp sequences of HLA-G antigen published at the Nolan Research Institute website. The highest concentration of sHLA-I is noted among women with HLA-G 10401 allele which differed significantly for the mean sHLA-I concentration calculated for all the remaining alleles (p<0.0001. The most prevalent alleles were: HLA-G 10101, 10102 and 10108 with sHLA-I concentrations among women bearing those alleles significantly lower in comparison to the HLA-G 10401 carriers (p<0.001. Allele 10101 and 10102 was related to the lower significantly plasma sHLA-I concentrations than 10108 allele (p<0.02. Lowest mean sHLA-G values were observed in the IVFf group with significant difference from the remaining groups (p<0.05. To conclude, sHLA-G molecules is associated to certain HLA-G alleles and imply that sHLA-G levels are under genetic control. Low concentration sHLA-G seems to be prognostically important in IVF failure.

  20. HLA-DPB1 and HLA Class I Confer Risk of and Protection from Narcolepsy

    Science.gov (United States)

    Ollila, Hanna M.; Ravel, Jean-Marie; Han, Fang; Faraco, Juliette; Lin, Ling; Zheng, Xiuwen; Plazzi, Giuseppe; Dauvilliers, Yves; Pizza, Fabio; Hong, Seung-Chul; Jennum, Poul; Knudsen, Stine; Kornum, Birgitte R.; Dong, Xiao Song; Yan, Han; Hong, Heeseung; Coquillard, Cristin; Mahlios, Joshua; Jolanki, Otto; Einen, Mali; Lavault, Sophie; Högl, Birgit; Frauscher, Birgit; Crowe, Catherine; Partinen, Markku; Huang, Yu Shu; Bourgin, Patrice; Vaarala, Outi; Désautels, Alex; Montplaisir, Jacques; Mack, Steven J.; Mindrinos, Michael; Fernandez-Vina, Marcelo; Mignot, Emmanuel

    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 H1N1, suggesting autoimmunity triggered by upper-airway infections. Additional effects of other HLA-DQ alleles have been reported consistently across multiple ethnic groups. Using over 3,000 case and 10,000 control individuals of European and Chinese background, we examined the effects of other HLA loci. After careful matching of HLA-DR and HLA-DQ in case and control individuals, we found strong protective effects of HLA-DPA1∗01:03-DPB1∗04:02 (DP0402; odds ratio [OR] = 0.51 [0.38–0.67], p = 1.01 × 10−6) and HLA-DPA1∗01:03-DPB1∗04:01 (DP0401; OR = 0.61 [0.47–0.80], p = 2.07 × 10−4) and predisposing effects of HLA-DPB1∗05:01 in Asians (OR = 1.76 [1.34–2.31], p = 4.71 × 10−05). Similar effects were found by conditional analysis controlling for HLA-DR and HLA-DQ with DP0402 (OR = 0.45 [0.38–0.55] p = 8.99 × 10−17) and DP0501 (OR = 1.38 [1.18–1.61], p = 7.11 × 10−5). HLA-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. PMID:25574827

  1. 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...

  2. HLA II class antigens and susceptibility to coeliac disease

    Directory of Open Access Journals (Sweden)

    Vojvodić Svetlana

    2011-01-01

    Full Text Available Coeliac disease (CD is a systemic autoimmune, complex and multifactorial disorder, which is caused by interactions between genetic and environmental factors. The only established genetic risk factors so far are the human leucocyte antigens. The aim of this study was to assess the distribution of II class human leukocyte antigens (HLA in patients with coeliac disease and to investigate the susceptibility to coeliac disease in family members. We typed HLA DR and DQ antigens in 37 patients from Vojvodina with coeliac disease, 23 first-degree relatives, and 210 controls, serologically using standard lymphocytotoxicity technique. HLA DQ5(1, DQ6(1, DR11(5, DQ7(3, DQ2 and DR15(2 were the most common antigens in the control group. Frequency of HLA DQ2, DR3 and DR7 was higher in CD patients than in the control group. The relative risks for HLA DQ2, DR3 and DR7 were 4.846, 6.986 and 2.106, respectively, while positive association was found between HLA DQ2 and DR3 and CD. Frequency of HLA DQ2, DR3 and DR16(2 was higher in first-degree relatives than in the control group while a positive association was found between HLA DQ2 and DR3. A negative association was found between HLA DQ5(1 and DQ6(1 in coeliac patients from Vojvodina and their relatives, in addition to HLA DR11(5 in the group of relatives (RR=0.363,PF=0.232. These findings indicate the impact of the HLA testing for CD in clinical practice in order to rule out the possibility to CD in doubtful cases or in at-risk subjects.

  3. HLA class I binding prediction via convolutional neural networks.

    Science.gov (United States)

    Vang, Yeeleng S; Xie, Xiaohui

    2017-09-01

    Many biological processes are governed by protein-ligand interactions. One such example is the recognition of self and non-self cells by the immune system. This immune response process is regulated by the major histocompatibility complex (MHC) protein which is encoded by the human leukocyte antigen (HLA) complex. Understanding the binding potential between MHC and peptides can lead to the design of more potent, peptide-based vaccines and immunotherapies for infectious autoimmune diseases. We apply machine learning techniques from the natural language processing (NLP) domain to address the task of MHC-peptide binding prediction. More specifically, we introduce a new distributed representation of amino acids, name HLA-Vec, that can be used for a variety of downstream proteomic machine learning tasks. We then propose a deep convolutional neural network architecture, name HLA-CNN, for the task of HLA class I-peptide binding prediction. Experimental results show combining the new distributed representation with our HLA-CNN architecture achieves state-of-the-art results in the majority of the latest two Immune Epitope Database (IEDB) weekly automated benchmark datasets. We further apply our model to predict binding on the human genome and identify 15 genes with potential for self binding. Codes to generate the HLA-Vec and HLA-CNN are publicly available at: https://github.com/uci-cbcl/HLA-bind . xhx@ics.uci.edu. Supplementary data are available at Bioinformatics online.

  4. Linkage and association of HLA class II genes with vitiligo in a Dutch population

    NARCIS (Netherlands)

    Zamani, M.; Spaepen, M.; Sghar, S. S.; Huang, C.; Westerhof, W.; Nieuweboer-Krobotova, L.; Cassiman, J. J.

    2001-01-01

    Serological typing of HLA has shown discrepancies in HLA associations with vitiligo in different ethnic populations. To perform genotyping of HLA class II genes on a Dutch vitiligo population in order clearly to identify susceptible and protective HLA alleles in vitiligo. HLA typing was carried out

  5. Endogenous HLA class II epitopes that are immunogenic in vivo show distinct behavior toward HLA-DM and its natural inhibitor HLA-DO.

    Science.gov (United States)

    Kremer, Anita N; van der Meijden, Edith D; Honders, Maria W; Goeman, Jelle J; Wiertz, Emmanuel J H J; Falkenburg, J H Frederik; Griffioen, Marieke

    2012-10-18

    CD4(+) T cells play a central role in adaptive immunity. The acknowledgment of their cytolytic effector function and the finding that endogenous antigens can enter the HLA class II processing pathway make CD4(+) T cells promising tools for immunotherapy. Expression of HLA class II and endogenous antigen, however, does not always correlate with T-cell recognition. We therefore investigated processing and presentation of endogenous HLA class II epitopes that induced CD4(+) T cells during in vivo immune responses. We demonstrate that the peptide editor HLA-DM allowed antigen presentation of some (DM-resistant antigens) but abolished surface expression of other natural HLA class II epitopes (DM-sensitive antigens). DM sensitivity was shown to be epitope specific, mediated via interaction between HLA-DM and the HLA-DR restriction molecule, and reversible by HLA-DO. Because of the restricted expression of HLA-DO, presentation of DM-sensitive antigens was limited to professional antigen-presenting cells, whereas DM-resistant epitopes were expressed on all HLA class II-expressing cells. In conclusion, our data provide novel insights into the presentation of endogenous HLA class II epitopes and identify intracellular antigen processing and presentation as a critical factor for CD4(+) T-cell recognition. This opens perspectives to exploit selective processing capacities as a new approach for targeted immunotherapy.

  6. Oligoclonal band phenotypes in MS differ in their HLA class II association, while specific KIR ligands at HLA class I show association to MS in general

    DEFF Research Database (Denmark)

    Gustavsen, Marte W; Viken, Marte K; Celius, Elisabeth G

    2014-01-01

    Multiple sclerosis (MS) patients have been reported to have different HLA class II allele profiles depending on oligoclonal bands (OCBs) in the cerebrospinal fluid, but HLA class I alleles and killer cell immunoglobulin-like receptor (KIR) ligands have not been studied. We investigated...... the association of HLA alleles and KIR ligands according to OCB status in MS patients (n=3876). Specific KIR ligands were associated with patients when compared to controls (n=3148), supporting a role for NK cells in MS pathogenesis. HLA class I alleles and KIR ligands did not differ between OCB phenotypes......, but HLA class II associations were convincingly replicated....

  7. Confirmation of HLA class II independent type 1 diabetes associations in the major histocompatibility complex including HLA-B and HLA-A

    Science.gov (United States)

    Howson, J. M. M.; Walker, N. M.; Clayton, D.; Todd, J. A.

    2009-01-01

    Aim Until recently, human leucocyte antigen (HLA) class II-independent associations with type 1 diabetes (T1D) in the Major Histocompatibility Complex (MHC) region were not adequately characterized owing to insufficient map coverage, inadequate statistical approaches and strong linkage disequilibrium spanning the entire MHC. Here we test for HLA class II-independent associations in the MHC using fine mapping data generated by the Type 1 Diabetes Genetics Consortium (T1DGC). Methods We have applied recursive partitioning to the modelling of the class II loci and used stepwise conditional logistic regression to test ~1534 loci between 29 and 34 Mb on chromosome 6p21, typed in 2240 affected sibpair (ASP) families. Results Preliminary analyses confirm that HLA-B (at 31.4 Mb), HLA-A (at 30.0 Mb) are associated with T1D independently of the class II genes HLA-DRB1 and HLA-DQB1 (P = 6.0 × 10−17 and 8.8 × 10−13, respectively). In addition, a second class II region of association containing the single-nucleotide polymorphism (SNP), rs439121, and the class II locus HLA-DPB1, was identified as a T1D susceptibility effect which is independent of HLA-DRB1, HLA-DQB1 and HLA-B (P = 9.2 × 10−8). A younger age-at-diagnosis of T1D was found for HLA-B*39 (P = 7.6 × 10−6), and HLA-B*38 was protective for T1D. Conclusions These analyses in the T1DGC families replicate our results obtained previously in ~2000 cases and controls and 850 families. Taking both studies together, there is evidence for four T1D-associated regions at 30.0 Mb (HLA-A), 31.4 Mb (HLA-B), 32.5 Mb (rs9268831/HLA-DRA) and 33.2 Mb (rs439121/HLA-DPB1) that are independent of HLA-DRB1/HLA-DQB1. Neither study found evidence of independent associations at HLA-C, HLA-DQA1 loci nor in the UBD/MAS1L or ITPR3 gene regions. These studies show that to find true class II-independent effects, large, well-powered sample collections are required and be genotyped with a dense map of markers. In addition, a robust

  8. Negative regulation by HLA-DO of MHC class II-restricted antigen processing.

    Science.gov (United States)

    Denzin, L K; Sant'Angelo, D B; Hammond, C; Surman, M J; Cresswell, P

    1997-10-03

    HLA-DM is a major histocompatibility complex (MHC) class II-like molecule that facilitates antigen processing by catalyzing the exchange of invariant chain-derived peptides (CLIP) from class II molecules for antigenic peptides. HLA-DO is a second class II-like molecule that physically associates with HLA-DM in B cells. HLA-DO was shown to block HLA-DM function. Purified HLA-DM-DO complexes could not promote peptide exchange in vitro. Expression of HLA-DO in a class II+ and DM+, DO- human T cell line caused the accumulation of class II-CLIP complexes, indicating that HLA-DO blocked DM function in vivo and suggesting that HLA-DO is an important modulator of class II-restricted antigen processing.

  9. KIR genes and HLA class I ligands in Gaucher disease.

    Science.gov (United States)

    Vairo, Filippo; Portela, Pâmela; Salim, Patrícia H; Jobim, Mariana; Netto, Cristina; Dorneles, Alicia; Mittlestadt, Suzana; Jobim, Luiz Fernando; Schwartz, Ida Vanessa D

    2013-03-01

    Gaucher disease (GD) is caused by reduced activity of the lysosomal enzyme glucocerebrosidase, which leads to a buildup of glucocerebroside within the cells and chronic stimulation of the immune system. GD is associated with clinical variability even in the same family, which suggests the influence of modifier genes. Natural killer (NK) cells play an important role in the immune response, and their number is decreased in GD. Killer-cell immunoglobulin-like receptors (KIR) regulate the activity of NK cells through an interaction with specific human leukocyte antigen (HLA) class I molecules on target cells. To analyze the variability of KIR genes in a sample of GD patients from Southern Brazil, and look for associations between variants and clinical manifestations. Thirty-one GD patients (24 mild, 4 moderate, and 3 severe) were included in the study. Fifteen KIR genes, HLA-C and HLA-Bw4 were analyzed using SSP-PCR. Clinical, biochemical, and radiological data were collected by means of a chart review. Age at symptom onset was associated with KIR2DL2 and KIR2DS2 in combination with the ligand HLA-C1 (p=0.038). Patients who have the HLA-C2 variant appear to have more mono- and polyclonal bands on protein electrophoresis (p=0.007, OR 21.3). There was no between-group significant difference in the frequencies of KIR/HLA variants. Although exploratory our data suggest a possible association of KIR/HLA variants and the severity of GD. Further study of KIR/HLA variants is required, as they seem to be a phenotype-modifying factor in this disease. Copyright © 2012 Elsevier B.V. All rights reserved.

  10. HLA class I and class II associations with ESRD in Saudi Arabian population.

    Directory of Open Access Journals (Sweden)

    Nuha Mahmoud Hamdi

    Full Text Available Chronic renal failure (CRF leads in the majority of instances to end stage renal disease (ESRD requiring renal replacement therapy. Our interest was to evaluate the possible associations of HLA class I and class II antigens with ESRD independent of other factors, in Saudi Arabia population.A retrospective study to determine the HLA class I and class II polymorphisms and their association with ESRD, was performed on 350 patients with ESRD, and 105 healthy unrelated control. Patients and control groups were typed by SSOP lumenix techniques. The alleles positively associated to the ESRD were: HLA-B*15, B*18, B*49 - DRB1*03, negatively associated alleles were A*26, HLA-B*39, B*50. The haplotypes positively associated with ESRD were: HLA-A*01-DRB1*13 and HLA-A*30-DRBI*03. The negatively associated haplotypes were: HLA-A*02-B*39, A*02-B*50, A*24-B*35, A*24-B*58, A*24-DRB1*16, A*68-DRB1*04, A*02-DQB1*03, A*29-DQB1*02, A*29-DOB1*05 and B*27-DRB1*07 and the last one is the most significant protective haplotypes.The high Relative Risk (RR observed and its statistical correlation reflect the strength of the described association between HLA antigens and ESRD.

  11. HLA Class I and Class II Associations with ESRD in Saudi Arabian Population

    Science.gov (United States)

    Hamdi, Nuha Mahmoud; Al-Hababi, Fadel Hassan; Eid, Amr Ekhlas

    2014-01-01

    Background Chronic renal failure (CRF) leads in the majority of instances to end stage renal disease (ESRD) requiring renal replacement therapy. Our interest was to evaluate the possible associations of HLA class I and class II antigens with ESRD independent of other factors, in Saudi Arabia population. Methodology A retrospective study to determine the HLA class I and class II polymorphisms and their association with ESRD, was performed on 350 patients with ESRD, and 105 healthy unrelated control. Patients and control groups were typed by SSOP lumenix techniques. The alleles positively associated to the ESRD were: HLA-B*15, B*18, B*49 - DRB1*03, negatively associated alleles were A*26, HLA-B*39, B*50. The haplotypes positively associated with ESRD were: HLA-A*01-DRB1*13 and HLA-A*30-DRBI*03. The negatively associated haplotypes were: HLA-A*02-B*39, A*02-B*50, A*24-B*35, A*24-B*58, A*24-DRB1*16, A*68-DRB1*04, A*02-DQB1*03, A*29-DQB1*02, A*29-DOB1*05 and B*27-DRB1*07 and the last one is the most significant protective haplotypes. Conclusion The high Relative Risk (RR) observed and its statistical correlation reflect the strength of the described association between HLA antigens and ESRD. PMID:25380295

  12. DNA polymorphism of HLA class II genes in alopecia areata

    DEFF Research Database (Denmark)

    Morling, N; Frentz, G; Fugger, L

    1992-01-01

    We investigated the DNA restriction polymorphism (RFLP) of the Major Histocompatibility Complex (MHC) class II genes: HLA-DQA, -DQB, -DPA, and -DPB in 20 Danish patients with alopecia areata (AA) and in healthy Danes. The frequency in AA of the DQB1*0301 and DQw7 associated DQB Bgl/II 4.2 kb...

  13. Proteome sampling by the HLA class I antigen processing pathway.

    Science.gov (United States)

    Hoof, Ilka; van Baarle, Debbie; Hildebrand, William H; Keşmir, Can

    2012-01-01

    The peptide repertoire that is presented by the set of HLA class I molecules of an individual is formed by the different players of the antigen processing pathway and the stringent binding environment of the HLA class I molecules. Peptide elution studies have shown that only a subset of the human proteome is sampled by the antigen processing machinery and represented on the cell surface. In our study, we quantified the role of each factor relevant in shaping the HLA class I peptide repertoire by combining peptide elution data, in silico predictions of antigen processing and presentation, and data on gene expression and protein abundance. Our results indicate that gene expression level, protein abundance, and rate of potential binding peptides per protein have a clear impact on sampling probability. Furthermore, once a protein is available for the antigen processing machinery in sufficient amounts, C-terminal processing efficiency and binding affinity to the HLA class I molecule determine the identity of the presented peptides. Having studied the impact of each of these factors separately, we subsequently combined all factors in a logistic regression model in order to quantify their relative impact. This model demonstrated the superiority of protein abundance over gene expression level in predicting sampling probability. Being able to discriminate between sampled and non-sampled proteins to a significant degree, our approach can potentially be used to predict the sampling probability of self proteins and of pathogen-derived proteins, which is of importance for the identification of autoimmune antigens and vaccination targets.

  14. c-myc down-regulates class I HLA expression in human melanomas

    NARCIS (Netherlands)

    Versteeg, R.; NOORDERMEER, I. A.; Krüse-Wolters, M.; Ruiter, D. J.; Schrier, P. I.

    1988-01-01

    Expression of class I HLA antigen has been shown to be reduced in a number of human tumours. Here we show that in a panel of 11 melanoma cell lines with variable class I HLA expression an inverse correlation exists between the mRNA levels of c-myc and class I HLA. This suggests that high expression

  15. Antigen Presentation by Individually Transferred HLA Class I Genes in HLA-A, HLA-B, HLA-C Null Human Cell Line Generated Using the Multiplex CRISPR-Cas9 System.

    Science.gov (United States)

    Hong, Cheol-Hwa; Sohn, Hyun-Jung; Lee, Hyun-Joo; Cho, Hyun-Il; Kim, Tai-Gyu

    Human leukocyte antigens (HLAs) are essential immune molecules that affect transplantation and adoptive immunotherapy. When hematopoietic stem cells or organs are transplanted with HLA-mismatched recipients, graft-versus-host disease or graft rejection can be induced by allogeneic immune responses. The function of each HLA allele has been studied using HLA-deficient cells generated from mutant cell lines or by RNA interference, zinc finger nuclease, and the CRISPR/Cas9 system. To improve HLA gene editing, we attempted to generate an HLA class I null cell line using the multiplex CRISPR/Cas9 system by targeting exons 2 and 3 of HLA-A, HLA-B, and HLA-C genes simultaneously. Multiplex HLA editing could induce the complete elimination of HLA class I genes by bi-allelic gene disruption on target sites which was defined by flow cytometry and target-specific polymerase chain reaction. Furthermore, artificial antigen-presenting cells were generated by transfer of a single HLA class I allele and co-stimulatory molecules into this novel HLA class I null cell line. Artificial antigen-presenting cells showed HLA-restricted antigen presentation following antigen processing and were successfully used for the efficient generation of tumor antigen-specific cytotoxic T cells in vitro. The efficient editing of HLA genes may provide a basis for universal cellular therapies and transplantation.

  16. Impact of genetic variations and transcriptional alterations of HLA class I genes on cervical cancer pathogenesis.

    Science.gov (United States)

    Das Ghosh, Damayanti; Mukhopadhyay, Indranil; Bhattacharya, Amrapali; Roy Chowdhury, Rahul; Mandal, Nidhu Ranjan; Roy, Sudipta; Sengupta, Sharmila

    2017-06-01

    In a novel attempt to understand the variations in DNA sequences underlying HLA class I alleles associated with HPV16-related CaCx, we determined the alleles by reconstructing SNP-based haplotypes from resequencing of the most polymorphic exons 2 and 3 of HLA-A, HLA-B and HLA-C. We also determined the impact of SNPs and transcriptional alterations of the genes on CaCx. A high density of SNPs was identified from resequencing. HLA expression was determined by real-time PCR. We identified that even a single associated HLA allele had many underlying SNP-based haplotypes. Out of the most frequent (≥5%) HLA class I alleles, HLA-B*40:06 and HLA-B*15:02 respectively imparted significant risk towards and protection from CaCx as well as HPV16 infection. Employing median-joining networks to detect clusters of sequence-variations for specific HLA alleles, we found the protective SNP-based signature, GAATTTA, in all SNP-based haplotypes of HLA-B*15:02 allele. The signature was derived from seven SNPs within HLA-B which were newly associated with the disease. Contrarily, similarly derived risk-signature, TTGCGCC, mapped only to 52% of SNP-based haplotypes of HLA-B*40:06 allele. This indicated that all SNP-based haplotypes underlying a particular associated HLA allele might or might not have a single signature of risk/protection. HLA-A, HLA-B and HLA-C expressions were downregulated among CaCx cases compared to asymptomatic infections and HPV-negative controls. HLA-A and HLA-B were repressed in both cases harbouring episomal and integrated HPV16, whereas HLA-C in only the latter. Novel genetic variations and differential downregulation-patterns of HLA class I have a significant bearing on HPV16-related CaCx pathogenesis. © 2017 UICC.

  17. Narcolepsy-Associated HLA Class I Alleles Implicate Cell-Mediated Cytotoxicity

    NARCIS (Netherlands)

    Tafti, M.; Lammers, G.J.; Dauvilliers, Y.; Overeem, S.; Mayer, G.; Nowak, J.; Pfister, C.; Dubois, V.; Eliaou, J.F.; Eberhard, H.P.; Liblau, R.; Wierzbicka, A.; Geisler, P.; Bassetti, C.L.; Mathis, J.; Lecendreux, M.; Khatami, R.; Heinzer, R.; Haba-Rubio, J.; Feketeova, E.; Baumann, C.R.; Kutalik, Z.; Tiercy, J.M.

    2016-01-01

    STUDY OBJECTIVES: Narcolepsy with cataplexy is tightly associated with the HLA class II allele DQB1*06:02. Evidence indicates a complex contribution of HLA class II genes to narcolepsy susceptibility with a recent independent association with HLA-DPB1. The cause of narcolepsy is supposed be an

  18. Differential expression of the HLA class I multigene family by human embryonal carcinoma and choriocarcinoma cell lines

    NARCIS (Netherlands)

    Rinke de Wit, T. F.; Vloemans, S.; van den Elsen, P. J.; Haworth, A.; Stern, P. L.

    1990-01-01

    We have studied the expression of both HLA class and the recently described HLA class I-like genes (HLA-E and HLA-6.0) in two human developmental tumor cell lines, that serologically could not be typed for HLA-A, -B, and -C. Evidence is presented that the teratocarcinoma Tera-2 stem cells express

  19. Homotypic aggregation of human cell lines by HLA class II-, class Ia- and HLA-G-specific monoclonal antibodies

    DEFF Research Database (Denmark)

    Odum, Niels; Ledbetter, J A; Martin, P

    1991-01-01

    adhesion between T and B cells by activating the CD18/CD11a (LFA-1) adhesion pathway. Here we report that monoclonal antibodies (mAb) against HLA-DR (L243, p4.1, HB10a, VI15) and certain broad class II reacting mAb (TU35, TU39), but not anti-DQ (TU22, Leu-10) mAb, induced homotypic aggregation of human......, but not the class I-negative parental line, 221, showed homotypic aggregation in response to an HLA-G specific mAb (87G) and a broad reacting class I-specific mAb (IOT2). Both cell lines responded with aggregation to anti-class II mAb (TU35). The anti-class I mAb, W6/32, had no effect on all cell lines tested......Major histocompatibility complex (MHC) class II molecules have been implicated in cell adhesion in two ways. In addition to the well-established role of class II antigens in low-affinity adhesion provided by interactions between class II and CD4, recent data indicated that class II may also induce...

  20. Proteome sampling by the HLA class I antigen processing pathway.

    Directory of Open Access Journals (Sweden)

    Ilka Hoof

    Full Text Available The peptide repertoire that is presented by the set of HLA class I molecules of an individual is formed by the different players of the antigen processing pathway and the stringent binding environment of the HLA class I molecules. Peptide elution studies have shown that only a subset of the human proteome is sampled by the antigen processing machinery and represented on the cell surface. In our study, we quantified the role of each factor relevant in shaping the HLA class I peptide repertoire by combining peptide elution data, in silico predictions of antigen processing and presentation, and data on gene expression and protein abundance. Our results indicate that gene expression level, protein abundance, and rate of potential binding peptides per protein have a clear impact on sampling probability. Furthermore, once a protein is available for the antigen processing machinery in sufficient amounts, C-terminal processing efficiency and binding affinity to the HLA class I molecule determine the identity of the presented peptides. Having studied the impact of each of these factors separately, we subsequently combined all factors in a logistic regression model in order to quantify their relative impact. This model demonstrated the superiority of protein abundance over gene expression level in predicting sampling probability. Being able to discriminate between sampled and non-sampled proteins to a significant degree, our approach can potentially be used to predict the sampling probability of self proteins and of pathogen-derived proteins, which is of importance for the identification of autoimmune antigens and vaccination targets.

  1. [Routine application of HLA class II oligotyping. Value of automatization].

    Science.gov (United States)

    Caillat-Zucman, S; Bach, J F

    1992-12-02

    HLA class II typing by DNA amplification and hybridization with allele-specific oligonucleotides has led to an improvement of the overall typing accuracy. In an attempt to apply this procedure to a large-scale analysis, we sought to implement an automation system using the Biomek 1,000 robotic work-station. This system allows a rapid preparation of many consecutive samples and avoids the risk of human errors. It is now routinely used in several laboratories.

  2. Human Leukocyte Antigen (HLA) Class I Restricted Epitope Discovery in Yellow Fewer and Dengue Viruses: Importance of HLA Binding Strength

    DEFF Research Database (Denmark)

    Lund, Ole; Nascimento, Eduardo J. M.; Maciel, Milton, Jr

    2011-01-01

    Epitopes from all available full-length sequences of yellow fever virus (YFV) and dengue fever virus (DENV) restricted by Human Leukocyte Antigen class I (HLA-I) alleles covering 12 HLA-I supertypes were predicted using the NetCTL algorithm. A subset of 179 predicted YFV and 158 predicted DENV...... epitopes were selected using the EpiSelect algorithm to allow for optimal coverage of viral strains. The selected predicted epitopes were synthesized and approximately 75% were found to bind the predicted restricting HLA molecule with an affinity, K(D), stronger than 500 nM. The immunogenicity of 25 HLA...... inoculated twice with the 17DD YFV vaccine strain. Three of the YFV A*02:01 restricted peptides activated T-cells from the infected mice in vitro. All three peptides that elicited responses had an HLA binding affinity of 2 nM or less. The results indicate the importance of the strength of HLA binding...

  3. HLA-G and classical HLA class I expression in primary colorectal cancer and associated liver metastases.

    Science.gov (United States)

    Swets, Marloes; König, Marion H; Zaalberg, Anniek; Dekker-Ensink, Neeltje G; Gelderblom, Hans; van de Velde, Cornelis J H; van den Elsen, Peter J; Kuppen, Peter J K

    2016-09-01

    De novo expression of HLA-G has been demonstrated in colorectal cancer. HLA-G, amongst others, inhibits natural killer cell function, contributing to host immune defense evasion. Another mechanism to escape anti-tumor immunity is loss of HLA class I. Therefore, we determined HLA-G and HLA class I expression on primary colorectal tumors and associated liver metastases, in order to get insight in the metastasizing process regarding escaping anti-tumor immunity. HLA-G expression was evaluated using three mAbs; 4H84, MEM-G/1 and MEM-G/2. In total 81 colorectal cancer patients were evaluated. Formalin-fixed paraffin-embedded tissue sections of primary tumors and associated liver metastases, were immunohistochemically stained. A concordance between expression or loss/downregulation in the primary tumor and associated liver metastasis regarding HLA class I expression was observed in 80% of the cases. In contrast with the hypothesis of escaping NK cell-killing, we demonstrated for each HLA-G detecting mAbs used in this study, that the majority of the primary tumors that positively stained for HLA-G did not express HLA-G in the associated liver metastasis. Furthermore, we revealed the existence of non-specific binding and in addition we found that the different epitopes of HLA-G detected by 4H84, MEM-G/1 and MEM-G/2 mAbs were expressed differentially in colorectal tumor tissues. Copyright © 2016 American Society for Histocompatibility and Immunogenetics. Published by Elsevier Inc. All rights reserved.

  4. Timely management of developing class III malocclusion

    OpenAIRE

    M R Yelampalli; M R Rachala

    2012-01-01

    Timing of orthodontic treatment, especially for children with developing class III malocclusions, has always been somewhat controversial, and definitive treatment tends to be delayed for severe class III cases. Developing class III patients with moderate to severe anterior crossbite and deep bite may need early intervention in some selected cases. Class III malocclusion may develop in children as a result of an inherent growth abnormality, i.e. true class III malocclusion, or as a result of p...

  5. Epigenetic priming restores the HLA class-I antigen processing machinery expression in Merkel cell carcinoma

    DEFF Research Database (Denmark)

    Ritter, Cathrin; Fan, Kaiji; Paschen, Annette

    2017-01-01

    Merkel cell carcinoma (MCC) is a rare and aggressive, yet highly immunogenic skin cancer. The latter is due to its viral or UV-associated carcinogenesis. For tumor progression MCC has to escape the host's immuno-surveillance, e.g. by loss of HLA class-I expression. Indeed, a reduced HLA class......-I expression was observed in MCC tumor tissues and MCC cell lines. This reduced HLA class-I surface expression is caused by an impaired expression of key components of the antigen processing machinery (APM), including LMP2 and LMP7 as well as TAP1 and TAP2. Notably, experimental provisions of HLA class......-I binding peptides restored HLA class-I surface expression on MCC cells. Silencing of the HLA class-I APM is due to histone deacetylation as inhibition of histone deacetylases (HDACs) not only induced acetylation of histones in the respective promoter regions but also re-expression of APM components. Thus...

  6. Peptide Binding to HLA Class I Molecules: Homogenous, High-Throughput Screening, and Affinity Assays

    DEFF Research Database (Denmark)

    Harndahl, Mikkel; Justesen, Sune Frederik Lamdahl; Lamberth, Kasper

    2009-01-01

    present a homogenous, proximity-based assay for detection of peptide binding to HLA class I molecules. It uses a conformation-dependent anti-HLA class I antibody, W6/32, as one tag and a biotinylated recombinant HLA class I molecule as the other tag, and a proximity-based signal is generated through...... the luminescent oxygen channeling immunoassay technology (abbreviated LOCI and commercialized as AlphaScreen (TM)). Compared with an enzyme-linked immunosorbent assay-based peptide-HLA class I binding assay, the LOCI assay yields virtually identical affinity measurements, although having a broader dynamic range...

  7. The Immunogenicity of HLA Class II Mismatches: The Predicted Presentation of Nonself Allo-HLA-Derived Peptide by the HLA-DR Phenotype of the Recipient Is Associated with the Formation of DSA.

    Science.gov (United States)

    Jucaud, Vadim

    2017-01-01

    The identification of permissible HLA class II mismatches can prevent DSA in mismatched transplantation. The HLA-DR phenotype of recipients contributes to DSA formation by presenting allo-HLA-derived peptides to T-helper cells, which induces the differentiation of B cells into plasma cells. Comparing the binding affinity of self and nonself allo-HLA-derived peptides for recipients' HLA class II antigens may distinguish immunogenic HLA mismatches from nonimmunogenic ones. The binding affinities of allo-HLA-derived peptides to recipients' HLA-DR and HLA-DQ antigens were predicted using the NetMHCIIpan 3.1 server. HLA class II mismatches were classified based on whether they induced DSA and whether self or nonself peptide was predicted to bind with highest affinity to recipients' HLA-DR and HLA-DQ. Other mismatch characteristics (eplet, hydrophobic, electrostatic, and amino acid mismatch scores and PIRCHE-II) were evaluated. A significant association occurred between DSA formation and the predicted HLA-DR presentation of nonself peptides (P = 0.0169; accuracy = 80%; sensitivity = 88%; specificity = 63%). In contrast, mismatch characteristics did not differ significantly between mismatches that induced DSA and the ones that did not, except for PIRCHE-II (P = 0.0094). This methodology predicts DSA formation based on HLA mismatches and recipients' HLA-DR phenotype and may identify permissible HLA mismatches to help optimize HLA matching and guide donor selection.

  8. The Immunogenicity of HLA Class II Mismatches: The Predicted Presentation of Nonself Allo-HLA-Derived Peptide by the HLA-DR Phenotype of the Recipient Is Associated with the Formation of DSA

    Science.gov (United States)

    2017-01-01

    The identification of permissible HLA class II mismatches can prevent DSA in mismatched transplantation. The HLA-DR phenotype of recipients contributes to DSA formation by presenting allo-HLA-derived peptides to T-helper cells, which induces the differentiation of B cells into plasma cells. Comparing the binding affinity of self and nonself allo-HLA-derived peptides for recipients' HLA class II antigens may distinguish immunogenic HLA mismatches from nonimmunogenic ones. The binding affinities of allo-HLA-derived peptides to recipients' HLA-DR and HLA-DQ antigens were predicted using the NetMHCIIpan 3.1 server. HLA class II mismatches were classified based on whether they induced DSA and whether self or nonself peptide was predicted to bind with highest affinity to recipients' HLA-DR and HLA-DQ. Other mismatch characteristics (eplet, hydrophobic, electrostatic, and amino acid mismatch scores and PIRCHE-II) were evaluated. A significant association occurred between DSA formation and the predicted HLA-DR presentation of nonself peptides (P = 0.0169; accuracy = 80%; sensitivity = 88%; specificity = 63%). In contrast, mismatch characteristics did not differ significantly between mismatches that induced DSA and the ones that did not, except for PIRCHE-II (P = 0.0094). This methodology predicts DSA formation based on HLA mismatches and recipients' HLA-DR phenotype and may identify permissible HLA mismatches to help optimize HLA matching and guide donor selection. PMID:28331856

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

    OpenAIRE

    Leite, Elza Regina Manzolli; Lima, Oswaldo Luiz Luz; Leite, Fábio Renato Manzolli; Costa, Paulo Inácio da

    2010-01-01

    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 tha...

  10. Extraembryonic expression of the human MHC class I gene HLA-G in transgenic mice

    Energy Technology Data Exchange (ETDEWEB)

    Schmidt, C.M.; Ehlenfeldt, R.G.; Athanasiou, M.C.; Duvick, L.A.; Orr, H.T. (Univ. of Minnesota, Minneapolis, MN (United States)); Hubert, H.

    1993-09-01

    Trophoblast, the only fetal tissue in direct contact with maternal cells, fails to express the polymorphic HLA class I molecules HLA-A and -B, but does express the nonpolymorphic class I molecule HLA-G. It is thought that HLA-G may provide some of the functions of a class I molecule without stimulating maternal immune rejection of the fetal semiallograft. As a first step in identifying the cis-acting DNA regulatory elements involved in the control of class I expression by extraembryonic tissue, several types of transgenic mice were produced. Two HLA-G genomic fragments were used, 5.7 and 6.0 kb in length. These include the entire HLA-G coding region, 1 kb of 3' flanking sequence, and 1.2 or 1.4 kb of 5' flanking sequence, respectively. A hybrid transgene, HLA-A2/G, was produced by replacing the 5' flanking sequence, first exon, and early first intron of HLA-G with the corresponding elements of HLA-A. Comparison of transgene mRNA expression patterns seen in HLA-A2/G and HLA-G transgenic mice suggests that 5' flanking sequences are largely responsible for the differing patterns of expression typical of the classical class I and HLA-G genes. Studies comparing the extraembryonic HLA-G expression levels of founder embryos transgenic for either the 5.7 - or 6.0-kb HLA-G transgene showed that the 6.0-kb transgene directed HLA-G expression far more efficiently than did the 5.7-kb HLA-G transgene, producing extraembryoinc HLA-G mRNA levels similar to those seen in human extraembryoinic tissues. The results of these studies suggest that the 250-bp fragment present at the extreme 5' end of the 6.0-kb HLA-G transgene and absent from the 5.7-kb HLA-G transgene contains an important positive regulatory element. This 250-bp fragment lies further upstream than any of the previously documented class I regulatory regions and may function as a locus control region.

  11. 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

    A line of investigation indicates that one or several genes in the human major histocompatibility complex (MHC) influences reproductive success. Studies have revealed associations between human leukocyte antigen (HLA) class II genes and risk of recurrent spontaneous abortion (RSA) and pre......-eclampsia. However, these genes are not expressed at the feto-maternal interface. Furthermore, associations between polymorphisms in the nonclassical HLA class Ib gene, HLA-G, and reproductive outcome have been demonstrated. HLA-G is expressed by extravillous trophoblast during pregnancy, making it a more obvious...... candidate gene for a possible influence on pregnancy outcome. HLA-G has immunomodulatory functions. We have studied linkage disequilibrium between HLA class II genes, primarily HLA-DRB1 alleles, and HLA-G alleles in women with RSA and their partners (n = 103) and in control women and their partners (n = 92...

  12. High-resolution HLA class I typing in the CEPH families: analysis of linkage disequilibrium among HLA loci.

    Science.gov (United States)

    Bugawan, T L; Klitz, W; Blair, A; Erlich, H A

    2000-11-01

    The HLA region on the short arm of chromosome 6 (6p21.3) contains the most polymorphic coding sequences in the human genome. High-resolution DNA-based HLA typing of population samples of the polymorphic class I loci, HLA-A, -B, and -C has only recently become feasible. Here, we report molecular HLA typing on family-based samples of European origin (the CEPH repository), which demonstrated very high polymorphism, with 20 A alleles, 38 B alleles and 19 C alleles in the sample of 248 independent haplotypes. In general, allele frequency distributions are consistently more even (lower observed homozygosity statistic) than expected from a past of selective neutrality suggesting a history of balancing selection. This was also true for the class II loci, DRB1, DQA1 and DQB1 in these samples, but not for the DPA1 and DPB1 loci, whose allelic frequency distributions were more skewed (higher observed homozygosity statistic) than expected under a neutral model. Although linkage disequilibrium is a prominent feature across the HLA region, only 19% of the eight locus haplotypes were sampled more than once. The relative age of some of the B alleles could be inferred from the pattern of B-C haplotypic associations. We suggest that the observed patterns of linkage disequilibrium reflect the operation of selection on nearly all HLA alleles.

  13. HLA class Ia and Ib molecules and FOXP3+ TILs in relation to the prognosis of malignant melanoma patients

    DEFF Research Database (Denmark)

    Melsted, Wenna Nascimento; Johansen, Lasse Lindholm; Lock-Andersen, Jørgen

    2017-01-01

    HLA class Ia (HLA-ABC) and HLA class Ib (HLA-E, -F and -G) molecules and FOXP3+ tumor-infiltrating lymphocytes (TILs) are often reported as relevant factors of tumor immune regulation. We investigated their expression as prognostic factors in 200 patients with primary cutaneous melanoma (PCM......). In our cohort, patients with tumors showing upregulation of HLA-ABC molecules had significantly thicker tumors (32% vs 7%, P

  14. Association of high HLA-E expression during acute cellular rejection and numbers of HLA class I leader peptide mismatches with reduced renal allograft survival.

    Science.gov (United States)

    Guberina, Hana; Rebmann, Vera; Wagner, Bettina; da Silva Nardi, Fabiola; Dziallas, Phillip; Dolff, Sebastian; Bienholz, Anja; Wohlschlaeger, Jeremias; Bankfalvi, Agnes; Heinemann, Falko M; Witzke, Oliver; Zoet, Yvonne M; Claas, Frans H J; Horn, Peter A; Kribben, Andreas; Doxiadis, Ilias I N

    2017-03-01

    Non-classical Human Leukocyte Antigen (HLA)-E preferentially presents leader peptides derived from classical HLA-class I molecules. HLA-E can trigger opposed immune responses by interacting with inhibitory NKG2A or by activating NKG2C receptors on NK and T-cells. We studied the impact of HLA-E on renal allograft survival during acute cellular rejection. HLA-E expression was up-regulated in acute cellular rejection (ACR) biopsies (n=12) compared to biopsies from 13 renal allografts with no rejection-signs. HLA-E up-regulation was correlated with numbers of HLA-class I leader peptide mismatches (p=0.04). CD8+ and CD56+ infiltrating cells correlated with HLA-E expression (pleader peptides might represent additional targets for immune-activating responses. Copyright © 2016 Elsevier GmbH. All rights reserved.

  15. Infectious mononucleosis-linked HLA class I single nucleotide polymorphism is associated with multiple sclerosis.

    Science.gov (United States)

    Jafari, Naghmeh; Broer, Linda; Hoppenbrouwers, Ilse A; van Duijn, Cornelia M; Hintzen, Rogier Q

    2010-11-01

    Multiple sclerosis is a presumed autoimmune disease associated with genetic and environmental risk factors such as infectious mononucleosis. Recent research has shown infectious mononucleosis to be associated with a specific HLA class I polymorphism. Our aim was to test if the infectious mononucleosis-linked HLA class I single nucleotide polymorphism (rs6457110) is also associated with multiple sclerosis. Genotyping of the HLA-A single nucleotide polymorphism rs6457110 using TaqMan was performed in 591 multiple sclerosis cases and 600 controls. The association of multiple sclerosis with the HLA-A single nucleotide polymorphism was tested using logistic regression adjusted for age, sex and HLA-DRB1*1501. HLA-A minor allele (A) is associated with multiple sclerosis (OR = 0.68; p = 4.08 × 10( -5)). After stratification for HLA-DRB1*1501 risk allele (T) carrier we showed a significant OR of 0.70 (p = 0.003) for HLA-A. HLA class I single nucleotide polymorphism rs6457110 is associated with infectious mononucleosis and multiple sclerosis, independent of the major class II allele, supporting the hypothesis that shared genetics may contribute to the association between infectious mononucleosis and multiple sclerosis.

  16. HLA Class II Antigen Expression in Colorectal Carcinoma Tumors as a Favorable Prognostic Marker

    Directory of Open Access Journals (Sweden)

    Giuseppe Sconocchia

    2014-01-01

    Full Text Available The goal of this study was to determine the frequency of HLA class II antigen expression in colorectal carcinoma (CRC tumors, its association with the clinical course of the disease, and the underlying mechanism(s. Two tissue microarrays constructed with 220 and 778 CRC tumors were stained with HLA-DR, DQ, and DP antigen-specific monoclonal antibody LGII-612.14, using the immunoperoxidase staining technique. The immunohistochemical staining results were correlated with the clinical course of the disease. The functional role of HLA class II antigens expressed on CRC cells was analyzed by investigating their in vitro interactions with immune cells. HLA class II antigens were expressed in about 25% of the 220 and 21% of the 778 tumors analyzed with an overall frequency of 23%. HLA class II antigens were detected in 19% of colorectal adenomas. Importantly, the percentage of stained cells and the staining intensity were significantly lower than those detected in CRC tumors. However, HLA class II antigen staining was weakly detected only in 5.4% of 37 normal mucosa tissues. HLA class II antigen expression was associated with a favorable clinical course of the disease. In vitro stimulation with interferon gamma (IFNγ induced HLA class II antigen expression on two of the four CRC cell lines tested. HLA class II antigen expression on CRC cells triggered interleukin-1α (IL-1α production by resting monocytes. HLA class II antigen expression in CRC tumors is a favorable prognostic marker. This association may reflect stimulation of IL-1α production by monocytes.

  17. HLA-DM is localized to conventional and unconventional MHC class II-containing endocytic compartments.

    Science.gov (United States)

    Pierre, P; Denzin, L K; Hammond, C; Drake, J R; Amigorena, S; Cresswell, P; Mellman, I

    1996-03-01

    HLA-DM molecules remove invariant (Ii) chain peptides from newly synthesized MHC class II complexes. Their localization may thus delineate compartments, e.g., MIIC, specialized for loading peptides onto class II molecules. In murine A20 B cells, however, DM is not restricted to specialized endosomal class II-containing vesicles (CIIV). Although DM was found in CIIV, it was also found throughout the endocytic pathway, principally in lysosomes devoid of class II molecules. In human lymphoblasts, HLA-DM was found in structures indistinguishable from late endosomes or lysosomes, although in these cells the lysosomes contained MHC class II molecules. Thus, the distribution of HLA-DM does not necessarily identify specialized class II compartments. Many "MIIC" may represent conventional lysosomes that accumulate MHC class II and HLA-DM in a number of cell types.

  18. Immunogenicity of HLA Class I and II Double Restricted Influenza A-Derived Peptides

    DEFF Research Database (Denmark)

    Pedersen, Sara Ram; Christensen, Jan Pravsgaard; Buus, Søren

    2016-01-01

    The aim of the present study was to identify influenza A-derived peptides which bind to both HLA class I and -II molecules and by immunization lead to both HLA class I and class II restricted immune responses. Eight influenza A-derived 9-11mer peptides with simultaneous binding to both HLA-A*02......:01 and HLA-DRB1*01:01 molecules were identified by bioinformatics and biochemical technology. Immunization of transgenic HLA-A*02:01/HLA-DRB1*01:01 mice with four of these double binding peptides gave rise to both HLA class I and class II restricted responses by CD8 and CD4 T cells, respectively, whereas...... four of the double binding peptides did result in HLA-A*02:01 restricted responses only. According to their cytokine profile, the CD4 T cell responses were of the Th2 type. In influenza infected mice, we were unable to detect natural processing in vivo of the double restricted peptides and in line...

  19. NetMHCIIpan-3.0, a common pan-specific MHC class II prediction method including all three human MHC class II isotypes, HLA-DR, HLA-DP and HLA-DQ

    DEFF Research Database (Denmark)

    Karosiene, Edita; Rasmussen, Michael; Blicher, Thomas

    2013-01-01

    importance for understanding the nature of immune responses and identifying T cell epitopes for the design of new vaccines and immunotherapies. Given the large number of MHC variants, and the costly experimental procedures needed to evaluate individual peptide–MHC interactions, computational predictions have......MHCIIpan-3.0 method is the first pan-specific predictor covering all HLA class II molecules with known sequences including HLA-DR, HLA-DP, and HLA-DQ. The NetMHCpan-3.0 method is available at http://www.cbs.dtu.dk/services/NetMHCIIpan-3.0....

  20. Classical and nonclassical HLA class I antigen and NK Cell-activating ligand changes in malignant cells: current challenges and future directions.

    Science.gov (United States)

    Chang, Chien-Chung; Campoli, Michael; Ferrone, Soldano

    2005-01-01

    Changes in classical and nonclassical HLA class I antigen and NK cell-activating ligand expression have been identified in malignant lesions. These changes, which are described in this chapter, are believed to play a major role in the clinical course of the disease since both HLA class I antigens and NK cell-activating ligands are critical to the interaction between tumor cells and components of both innate and adaptive immune systems. Nevertheless, there is still debate in the literature about the biologic and functional significance of HLA class I antigen and NK cell-activating ligand abnormalities in malignant lesions. The reasons for this debate are reviewed. They include (i) the incomplete association between classical HLA class I antigen changes and the clinical course of the disease; (ii) the relatively limited number of malignant lesions that have been analyzed for nonclassical HLA class I antigen and NK cell-activating ligand expression; and (iii) the conflicting data regarding the role of immunoselection in the generation of malignant cells with HLA antigen and NK cell-activating ligand abnormalities. The technical limitations associated with the assessment of HLA antigen and NK cell-activating ligand expression in malignant lesions as well as the immunological and nonimmunological variables that may confound the impact of HLA antigen and NK cell-activating ligand changes on the clinical course of the disease are also discussed. Future studies aimed at overcoming these limitations and characterizing these variables are expected to provide a solution to the current debate regarding the significance of HLA class I antigen and NK cell-activating ligand abnormalities in malignant lesions.

  1. HLA-DO is a negative modulator of HLA-DM-mediated MHC class II peptide loading

    NARCIS (Netherlands)

    van Ham, S. M.; Tjin, E. P.; Lillemeier, B. F.; Grüneberg, U.; van Meijgaarden, K. E.; Pastoors, L.; Verwoerd, D.; Tulp, A.; Canas, B.; Rahman, D.; Ottenhoff, T. H.; Pappin, D. J.; Trowsdale, J.; Neefjes, J.

    1997-01-01

    Class II molecules of the major histocompatibility complex become loaded with antigenic peptides after dissociation of invariant chainderived peptides (CLIP) from the peptide-binding groove. The human leukocyte antigen (HLA)-DM is a prerequisite for this process, which takes place in specialised

  2. Toxoplasma gondii peptide ligands open the gate of the HLA class I binding groove

    DEFF Research Database (Denmark)

    McMurtrey, Curtis; Trolle, Thomas; Sansom, Tiffany

    2016-01-01

    HLA class I presentation of pathogen-derived peptide ligands is essential for CD8+ T cell recognition of Toxoplasma gondii infected cells. Currently, little data exist pertaining to peptides that are presented after T. gondii infection. Herein we purify HLA-A*02:01 complexes from T. gondii infected...

  3. A detailed comparison of peptides presented by different HLA class I loci: an in silico approach

    NARCIS (Netherlands)

    Rao, X.

    2012-01-01

    Human Leukocyte Antigen (HLA) class I is a group of genes located on human chromosome 6 which play a crucial role in initiating potentially protective immune responses, by presenting pathogen-derived peptides to CD8+ T cells and thus targeting infected cells for elimination. Compare to other HLA

  4. DNA polymorphism of HLA class II genes in primary biliary cirrhosis

    DEFF Research Database (Denmark)

    Morling, N; 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...

  5. HLA class Ib molecules and immune cells in pregnancy and preeclampsia

    Directory of Open Access Journals (Sweden)

    Snezana eDjurisic

    2014-12-01

    Full Text Available Despite decades of research, the highly prevalent pregnancy complication preeclampsia, ‘the disease of theories’, has remained an enigma. Indeed, the etiology of preeclampsia is largely unknown. A compiling amount of studies indicate that the pathological basis involves a complex array of genetic predisposition and immunological maladaptation, and that a contribution from the mother, the father and the fetus is likely to be important. The Human Leukocyte Antigen (HLA –G is an increasing focus of research in relation to preeclampsia. The HLA-G molecule is primarily expressed by the extravillous trophoblast cells lining the placenta together with the two other HLA class Ib molecules, HLA-E and HLA-F. Soluble isoforms of HLA-G have been detected in the early endometrium, the matured cumulus-oocyte complex, maternal blood of pregnant women, in umbilical cord blood, and lately, in seminal plasma. HLA-G is believed to be involved in modulating immune responses in the context of vascular remodeling during pregnancy as well as in dampening potential harmful immune attacks raised against the semi-allogeneic fetus. In addition, HLA-G genetic variants are associated with both membrane-bound and soluble forms of HLA-G, and, in some studies, with preeclampsia. In this review, a genetic contribution from the mother, the father and the fetus, together with the presence and function of various immune cells of relevance in pregnancy, are reviewed in relation to HLA-G and preeclampsia.

  6. HLA Class Ib Molecules and Immune Cells in Pregnancy and Preeclampsia

    Science.gov (United States)

    Djurisic, Snezana; Hviid, Thomas Vauvert F.

    2014-01-01

    Despite decades of research, the highly prevalent pregnancy complication preeclampsia, “the disease of theories,” has remained an enigma. Indeed, the etiology of preeclampsia is largely unknown. A compiling amount of studies indicates that the pathological basis involves a complex array of genetic predisposition and immunological maladaptation, and that a contribution from the mother, the father, and the fetus is likely to be important. The Human Leukocyte Antigen (HLA)-G is an increasing focus of research in relation to preeclampsia. The HLA-G molecule is primarily expressed by the extravillous trophoblast cells lining the placenta together with the two other HLA class Ib molecules, HLA-E and HLA-F. Soluble isoforms of HLA-G have been detected in the early endometrium, the matured cumulus–oocyte complex, maternal blood of pregnant women, in umbilical cord blood, and lately, in seminal plasma. HLA-G is believed to be involved in modulating immune responses in the context of vascular remodeling during pregnancy as well as in dampening potential harmful immune attacks raised against the semi-allogeneic fetus. In addition, HLA-G genetic variants are associated with both membrane-bound and soluble forms of HLA-G, and, in some studies, with preeclampsia. In this review, a genetic contribution from the mother, the father, and the fetus, together with the presence and function of various immune cells of relevance in pregnancy are reviewed in relation to HLA-G and preeclampsia. PMID:25566263

  7. HLA-class II genes in Mexican Amerindian Mayas: relatedness with Guatemalan Mayans and other populations.

    Science.gov (United States)

    Vargas-Alarcón, Gilberto; Granados, Julio; Pérez-Hernández, Nonanzit; Rodríguez-Pérez, José Manuel; Canto-Cetina, Thelma; Coral-Vázquez, Ramón Mauricio; Areces, Cristina; Gómez-Prieto, Pablo; Arnaiz-Villena, Antonio

    2011-01-01

    We analyzed the HLA class II allele frequencies in 50 healthy unrelated Mayan individuals. The relationship with other worldwide populations was studied by using HLA data from 71 different populations. The most frequent alleles were HLA-DRB1*04, HLA-DRB1*01, HLA-DQB1*0302 and HLA-DQB1*0501. When comparisons with other Mexican Amerindian groups were made, some differences were observed. Mayans showed an increased frequency of HLA-DRB1*01 when compared to Nahuas, Mayos, Teenek and Mazatecans (p Nahuas (p Nahuas and Mazatecans (p Nahuas, Mayos, Teenek and Mazatecans (p Nahuas was found. Neighbour Joining dendrogram shows that Mexican Mayans are genetically close to some of the most ancient groups living in Mexico and some South American Amerindians. However, Guatemalan Mayans do not cluster together with Mexican Mayas showing that languages do not correlate with genes, particularly in Amerindians. The data corroborate the restricted polymorphism of HLA-DRB1 and DQB1 alleles and the high frequency of HLA-DRB1*04 and HLA-DQB1*0302 in Mayans from Mexico.

  8. Inhibition of HLA-DM Mediated MHC Class II Peptide Loading by HLA-DO Promotes Self Tolerance

    OpenAIRE

    Denzin, Lisa K.

    2013-01-01

    Major histocompatibility class II (MHCII) molecules are loaded with peptides derived from foreign and self-proteins within the endosomes and lysosomes of antigen presenting cells (APCs). This process is mediated by interaction of MHCII with the conserved, non-polymorphic MHCII like molecule HLA-DM (DM). DM activity is directly opposed by HLA-DO (DO), another conserved, non-polymorphic MHCII like molecule. DO is an MHCII substrate mimic. Binding of DO to DM prevents MHCII from binding to DM, t...

  9. HLA class I haplotype diversity is consistent with selection for frequent existing haplotypes.

    Science.gov (United States)

    Alter, Idan; Gragert, Loren; Fingerson, Stephanie; Maiers, Martin; Louzoun, Yoram

    2017-08-01

    The major histocompatibility complex (MHC) contains the most polymorphic genetic system in humans, the human leukocyte antigen (HLA) genes of the adaptive immune system. High allelic diversity in HLA is argued to be maintained by balancing selection, such as negative frequency-dependent selection or heterozygote advantage. Selective pressure against immune escape by pathogens can maintain appreciable frequencies of many different HLA alleles. The selection pressures operating on combinations of HLA alleles across loci, or haplotypes, have not been extensively evaluated since the high HLA polymorphism necessitates very large sample sizes, which have not been available until recently. We aimed to evaluate the effect of selection operating at the HLA haplotype level by analyzing HLA A~C~B~DRB1~DQB1 haplotype frequencies derived from over six million individuals genotyped by the National Marrow Donor Program registry. In contrast with alleles, HLA haplotype diversity patterns suggest purifying selection, as certain HLA allele combinations co-occur in high linkage disequilibrium. Linkage disequilibrium is positive (Dij'>0) among frequent haplotypes and negative (Dij'haplotypes. Fitting the haplotype frequency distribution to several population dynamics models, we found that the best fit was obtained when significant positive frequency-dependent selection (FDS) was incorporated. Finally, the Ewens-Watterson test of homozygosity showed excess homozygosity for 5-locus haplotypes within 23 US populations studied, with an average Fnd of 28.43. Haplotype diversity is most consistent with purifying selection for HLA Class I haplotypes (HLA-A, -B, -C), and was not inferred for HLA Class II haplotypes (-DRB1 and-DQB1). We discuss our empirical results in the context of evolutionary theory, exploring potential mechanisms of selection that maintain high linkage disequilibrium in MHC haplotype blocks.

  10. LILRB2 interaction with HLA class I correlates with control of HIV-1 infection.

    Directory of Open Access Journals (Sweden)

    Arman A Bashirova

    2014-03-01

    Full Text Available Natural progression of HIV-1 infection depends on genetic variation in the human major histocompatibility complex (MHC class I locus, and the CD8+ T cell response is thought to be a primary mechanism of this effect. However, polymorphism within the MHC may also alter innate immune activity against human immunodeficiency virus type 1 (HIV-1 by changing interactions of human leukocyte antigen (HLA class I molecules with leukocyte immunoglobulin-like receptors (LILR, a group of immunoregulatory receptors mainly expressed on myelomonocytic cells including dendritic cells (DCs. We used previously characterized HLA allotype-specific binding capacities of LILRB1 and LILRB2 as well as data from a large cohort of HIV-1-infected individuals (N = 5126 to test whether LILR-HLA class I interactions influence viral load in HIV-1 infection. Our analyses in persons of European descent, the largest ethnic group examined, show that the effect of HLA-B alleles on HIV-1 control correlates with the binding strength between corresponding HLA-B allotypes and LILRB2 (p = 10(-2. Moreover, overall binding strength of LILRB2 to classical HLA class I allotypes, defined by the HLA-A/B/C genotypes in each patient, positively associates with viral replication in the absence of therapy in patients of both European (p = 10(-11-10(-9 and African (p = 10(-5-10(-3 descent. This effect appears to be driven by variations in LILRB2 binding affinities to HLA-B and is independent of individual class I allelic effects that are not related to the LILRB2 function. Correspondingly, in vitro experiments suggest that strong LILRB2-HLA binding negatively affects antigen-presenting properties of DCs. Thus, we propose an impact of LILRB2 on HIV-1 disease outcomes through altered regulation of DCs by LILRB2-HLA engagement.

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

    Directory of Open Access Journals (Sweden)

    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.

  12. Sequence and Phylogenetic Analysis of the Untranslated Promoter Regions for HLA Class I Genes.

    Science.gov (United States)

    Ramsuran, Veron; Hernández-Sanchez, Pedro G; O'hUigin, Colm; Sharma, Gaurav; Spence, Niamh; Augusto, Danillo G; Gao, Xiaojiang; García-Sepúlveda, Christian A; Kaur, Gurvinder; Mehra, Narinder K; Carrington, Mary

    2017-03-15

    Polymorphisms located within the MHC have been linked to many disease outcomes by mechanisms not yet fully understood in most cases. Variants located within untranslated regions of HLA genes are involved in allele-specific expression and may therefore underlie some of these disease associations. We determined sequences extending nearly 2 kb upstream of the transcription start site for 68 alleles from 57 major lineages of classical HLA class I genes. The nucleotide diversity within this promoter segment roughly follows that seen within the coding regions, with HLA-B showing the highest (∼1.9%), followed by HLA-A (∼1.8%), and HLA-C showing the lowest diversity (∼0.9%). Despite its greater diversity, HLA-B mRNA expression levels determined in 178 European Americans do not vary in an allele- or lineage-specific manner, unlike the differential expression levels of HLA-A or HLA-C reported previously. Close proximity of promoter sequences in phylogenetic trees is roughly reflected by similarity of expression pattern for most HLA-A and -C loci. Although promoter sequence divergence might impact promoter activity, we observed no clear link between the phylogenetic structures as represented by pairwise nucleotide differences in the promoter regions with estimated differences in mRNA expression levels for the classical class I loci. Further, no pair of class I loci showed coordinated expression levels, suggesting that distinct mechanisms across loci determine their expression level under nonstimulated conditions. These data serve as a foundation for more in-depth analysis of the functional consequences of promoter region variation within the classical HLA class I loci. Copyright © 2017 by The American Association of Immunologists, Inc.

  13. HLA II class alleles in juvenile idiopathic arthritis patients with and without temporomandibular joint arthritis

    OpenAIRE

    D?vidsone, Zane; Egl?te, Je?ena; Lazareva, Arina; Dzelz?te, Sarm?te; ?antere, Ruta; B?rzi?a, Dace; Sta??vi?a, Valda

    2016-01-01

    Background Temporomandibular joint (TMJ) arthritis is seen very often (38?87?%) in children with juvenile idiopathic arthritis (JIA). With contrast enhanced magnetic resonance imaging (MRI) we can detect more cases of TMJ arthritis than ever before. Previous studies show that HLA II class alleles may have protective or risk importance in JIA subtypes. Our objective is to identify HLA II class alleles of risk and protection in JIA patients with TMJ arthritis. Methods During the period from 201...

  14. Genes, genetics, and Class III malocclusion.

    Science.gov (United States)

    Xue, F; Wong, R W K; Rabie, A B M

    2010-05-01

    To present current views that are pertinent to the investigation of the genetic etiology of Class III malocclusion. Class III malocclusion is thought to be a polygenic disorder that results from an interaction between susceptibility genes and environmental factors. However, research on family pedigrees has indicated that Class III malocclusion might also be a monogenic dominant phenotype. Recent studies have reported that genes that encode specific growth factors or other signaling molecules are involved in condylar growth under mechanical strain. These genes, which include Indian hedgehog homolog (IHH), parathyroid-hormone like hormone (PTHLH), insulin-like growth factor-1 (IGF-1), and vascular endothelial growth factor (VEGF), and variations in their levels of expression play an important role in the etiology of Class III malocclusion. In addition, genome-wide scans have revealed chromosomal loci that are associated with Class III malocclusion. It is likely that chromosomal loci 1p36, 12q23, and 12q13 harbor genes that confer susceptibility to Class III malocclusion. In a case-control association study, we identified erythrocyte membrane protein band 4.1 (EPB41) to be a new positional candidate gene that might be involved in susceptibility to mandibular prognathism. Most of the earlier studies on the genetic etiology of Class III malocclusion have focused on the patterns of inheritance of this phenotype. Recent investigations have focused on understanding the genetic variables that affect Class III malocclusion and might provide new approaches to uncovering the genetic etiology of this phenotype.

  15. Malocclusion class III treatment in teething decidua.

    OpenAIRE

    Chávez Sevillano, Manuel Gustavo; Departamento Académico de Estomatología Pediátrica, sección Ortodoncia. Facultad de Odontología UNMSM. Lima – Perú.

    2014-01-01

    According as age increases, growth decreases and Class III skeletal patterns become more stable. The objective of Class III malocclusion’s treatment in primary dentition is to get a favorable environment to achieve a better dentofacial development. This article’s objective is to give a theorical summary about treatment of Class III malocclusions in primary dentition, and to present a case report. A medida que aumenta la edad, la cuantía de crecimiento disminuye y las clases III esquelética...

  16. Vertical hepatitis C virus transmission is not related to mother-child class-1 HLA concordance.

    Science.gov (United States)

    Azzari, C; Indolfi, G; Betti, L; Moriondo, M; Massai, C; Becciolini, L; Bertelli, L; Poggi, G M; De Martino, M; Resti, M

    2007-01-01

    Mother-child human leukocyte antigen (HLA)diversity is protective for vertical transmission of some viruses. The aim of this study is to evaluate the role of mother-child HLA diversity on hepatitis C virus (HCV) vertical transmission. Forty consecutive HCV infected and 46 consecutive control uninfected children born to HCV-RNA positive mothers were evaluated for HLA class-1 type concordance with their mothers. No significant difference in the degree of HLA concordance was found between HCV infected and uninfected children both when A, B, C (p=0.30) and when only A and B alleles were evaluated (p=0.59). Mother-infant HLA concordance does not affect HCV vertical transmission.

  17. Association between HLA-Class I and HLA-Class II Alleles and Mycobacterium Tuberculosis Infection in Iraqi Patients from Baghdad City

    Directory of Open Access Journals (Sweden)

    Nidhal Abdulmohaimen Mohammed

    2014-03-01

    Full Text Available Background: Pulmonary tuberculosis (PT is one of the endemic diseases in Iraq, and among the suggested predisposing factors are alleles of the human leukocyte antigen (HLA system. We sought to investigate the association between HLA-class I (A and B and -class II (DR and DQ alleles in a sample of PT Iraqi patients. Methods: lymphocytes of 105 PT patients and 40 controls were phenotyped for HLA-A, -B, -DR, and -DQ alleles by means of the microlymphocytotoxicity test using a panel of monoclonal antisera. Results: HLA frequencies of B18 (16.2 vs. 2.5%; OD=7.53 and DR1 (51.4 vs. 10.0%; OD=9.53 alleles were significantly increased in the patients as compared with the controls, while B5 (6.7 vs. 25.0%, DR8 (1.9 vs. 17.5%, and DQ3 (11.4 vs. 45.0% alleles were significantly decreased. However, a significant corrected level was maintained for only DR1, DR8, and DQ3 alleles (Pc=1.9×10-5, 0.02 and 1.0×10-4, respectively. Conclusion: The results confirm the predisposing and protecting roles of HLA alleles in PT.

  18. Timely management of developing class III malocclusion

    Directory of Open Access Journals (Sweden)

    M R Yelampalli

    2012-01-01

    Full Text Available Timing of orthodontic treatment, especially for children with developing class III malocclusions, has always been somewhat controversial, and definitive treatment tends to be delayed for severe class III cases. Developing class III patients with moderate to severe anterior crossbite and deep bite may need early intervention in some selected cases. Class III malocclusion may develop in children as a result of an inherent growth abnormality, i.e. true class III malocclusion, or as a result of premature occlusal contacts causing forward functional shift of the mandible, which is known as pseudo class III malocclusion. These cases, if not treated at the initial stage of development, interfere with normal growth of the jaw bases and may result in severe facial deformities. The treatment should be carried out as early as possible for permitting normal growth of the skeletal bases. This paper deals with the selection of an appropriate appliance from the various current options available for early intervention in developing class III malocclusion through two case reports.

  19. Timely management of developing class III malocclusion.

    Science.gov (United States)

    Yelampalli, M R; Rachala, M R

    2012-01-01

    Timing of orthodontic treatment, especially for children with developing class III malocclusions, has always been somewhat controversial, and definitive treatment tends to be delayed for severe class III cases. Developing class III patients with moderate to severe anterior crossbite and deep bite may need early intervention in some selected cases. Class III malocclusion may develop in children as a result of an inherent growth abnormality, i.e. true class III malocclusion, or as a result of premature occlusal contacts causing forward functional shift of the mandible, which is known as pseudo class III malocclusion. These cases, if not treated at the initial stage of development, interfere with normal growth of the jaw bases and may result in severe facial deformities. The treatment should be carried out as early as possible for permitting normal growth of the skeletal bases. This paper deals with the selection of an appropriate appliance from the various current options available for early intervention in developing class III malocclusion through two case reports.

  20. CEPHALOMETRIC FEATURES OF CLASS III MALOCCLUSION.

    Science.gov (United States)

    Zegan, Georgeta; Dascălu, Cristina; Mavru, R B; Anistoroaei, Daniela

    2015-01-01

    The study aimed to identify quantitative and relational characteristics of bone, dental and soft tissue structures for Class III malocclusion, according to gender and age range. 60 conventional lateral cephalograms were divided into two groups according to ANB angle: the group of cases with skeletal Class III (n = 36) and a control group with skeletal Class I (n = 24). There were performed 53 digital cephalometric measurements according to Steiner, Tweed and Jarabak analyzes. The Kolmogorov-Smirnov, t-student and Levene tests were used to find the characteristics of Class III, using SPSS 16.0 for Windows. We found 14 parameters that distinguished the two classes disorders (the angles SNB, SND, FMA, IMPA, MeGoOcP, Mand 1-MeGo, NSAr, ArGoMe, NGoMe and SNPog; the distances Ao-Bo and lu-NPog; Holdaway and AFH ratios) and 3 parameters for the Class III age ranges (NGoAr angle, Ls-NsPog' distance and S-Ar:Ar-Go ratio) (p ≤ 0.05). There were found no significant differences between genders for skeletal Class III. Emphasizing the cephalometric characteristics of Class III malocclusion, with the overall growth together with dental and occlusion development, requires early orthodontic therapy.

  1. HLA-E: strong association with beta2-microglobulin and surface expression in the absence of HLA class I signal sequence-derived peptides.

    Science.gov (United States)

    Lo Monaco, Elisa; Sibilio, Leonardo; Melucci, Elisa; Tremante, Elisa; Suchànek, Miloslav; Horejsi, Vaclav; Martayan, Aline; Giacomini, Patrizio

    2008-10-15

    The nonclassical class I HLA-E molecule folds in the presence of peptide ligands donated by the signal sequences of permissive class I HLA alleles, with the aid of TAP and tapasin. To identify HLA-E-specific Abs, four monoclonals of the previously described MEM series were screened by isoelectric focusing (IEF) blot and immunoprecipitation/IEF on >30 single-allele class I transfectants and HLA-homozygous B lymphoid cells coexpressing HLA-E and HLA-A, -B, -C, -F, or -G. Despite their HLA-E-restricted reactivity patterns (MEM-E/02 in IEF blot; MEM-E/07 and MEM-E/08 in immunoprecipitation), all of the MEM Abs unexpectedly reacted with beta(2)-microglobulin (beta(2)m)-free and denatured (but not beta(2)m-associated and folded) HLA-E H chains. Remarkably, other HLA-E-restricted Abs were also reactive with free H chains. Immunodepletion, in vitro assembly, flow cytometry, and three distinct surface-labeling methods, including a modified (conformation-independent) biotin-labeling assay, revealed the coexistence of HLA-E conformers with unusual and drastically antithetic features. MEM-reactive conformers were thermally unstable and poorly surface expressed, as expected, whereas beta(2)m-associated conformers were either unstable and weakly reactive with the prototypic conformational Ab W6/32, or exceptionally stable and strongly reactive with Abs to beta(2)m even in cells lacking permissive alleles (721.221), TAP (T2), or tapasin (721.220). Noncanonical, immature (endoglycosidase H-sensitive) HLA-E glycoforms were surface expressed in these cells, whereas mature glycoforms were exclusively expressed (and at much lower levels) in cells carrying permissive alleles. Thus, HLA-E is a good, and not a poor, beta(2)m assembler, and TAP/tapasin-assisted ligand donation is only one, and possibly not even the major, pathway leading to its stabilization and surface expression.

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

    Science.gov (United States)

    Ruiz-Extremera, A; Pavón-Castillero, E J; Florido, M; Muñoz de Rueda, P; Muñoz-Gámez, J A; Casado, J; Carazo, A; Quiles, R; Jiménez-Ruiz, S M; Gila, A; Luna, J D; León, J; Salmerón, J

    2017-01-01

    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

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

    Directory of Open Access Journals (Sweden)

    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

  4. Characterization of the Endothelial Cell Cytoskeleton following HLA Class I Ligation

    Science.gov (United States)

    Ziegler, Mary E.; Souda, Puneet; Jin, Yi-Ping; Whitelegge, Julian P.; Reed, Elaine F.

    2012-01-01

    Background Vascular endothelial cells (ECs) are a target of antibody-mediated allograft rejection. In vitro, when the HLA class I molecules on the surface of ECs are ligated by anti-HLA class I antibodies, cell proliferation and survival pathways are activated and this is thought to contribute to the development of antibody-mediated rejection. Crosslinking of HLA class I molecules by anti-HLA antibodies also triggers reorganization of the cytoskeleton, which induces the formation of F-actin stress fibers. HLA class I induced stress fiber formation is not well understood. Methodology and Principal Findings The present study examines the protein composition of the cytoskeleton fraction of ECs treated with HLA class I antibodies and compares it to other agonists known to induce alterations of the cytoskeleton in endothelial cells. Analysis by tandem mass spectrometry revealed unique cytoskeleton proteomes for each treatment group. Using annotation tools a candidate list was created that revealed 12 proteins, which were unique to the HLA class I stimulated group. Eleven of the candidate proteins were phosphoproteins and exploration of their predicted kinases provided clues as to how these proteins may contribute to the understanding of HLA class I induced antibody-mediated rejection. Three of the candidates, eukaryotic initiation factor 4A1 (eIF4A1), Tropomyosin alpha 4-chain (TPM4) and DDX3X, were further characterized by Western blot and found to be associated with the cytoskeleton. Confocal microscopy analysis showed that class I ligation stimulated increased eIF4A1 co-localization with F-actin and paxillin. Conclusions/Significance Colocalization of eIF4A1 with F-actin and paxillin following HLA class I ligation suggests that this candidate protein could be a target for understanding the mechanism(s) of class I mediated antibody-mediated rejection. This proteomic approach for analyzing the cytoskeleton of ECs can be applied to other agonists and various cells types

  5. Narcolepsy-Associated HLA Class I Alleles Implicate Cell-Mediated Cytotoxicity

    Science.gov (United States)

    Tafti, Mehdi; Lammers, Gert J.; Dauvilliers, Yves; Overeem, Sebastiaan; Mayer, Geert; Nowak, Jacek; Pfister, Corinne; Dubois, Valérie; Eliaou, Jean-François; Eberhard, Hans-Peter; Liblau, Roland; Wierzbicka, Aleksandra; Geisler, Peter; Bassetti, Claudio L.; Mathis, Johannes; Lecendreux, Michel; Khatami, Ramin; Heinzer, Raphaël; Haba-Rubio, José; Feketeova, Eva; Baumann, Christian R.; Kutalik, Zoltán; Tiercy, Jean-Marie

    2016-01-01

    Study Objectives: Narcolepsy with cataplexy is tightly associated with the HLA class II allele DQB1*06:02. Evidence indicates a complex contribution of HLA class II genes to narcolepsy susceptibility with a recent independent association with HLA-DPB1. The cause of narcolepsy is supposed be an autoimmune attack against hypocretin-producing neurons. Despite the strong association with HLA class II, there is no evidence for CD4+ T-cell-mediated mechanism in narcolepsy. Since neurons express class I and not class II molecules, the final effector immune cells involved might include class I-restricted CD8+ T-cells. Methods: HLA class I (A, B, and C) and II (DQB1) genotypes were analyzed in 944 European narcolepsy with cataplexy patients and in 4,043 control subjects matched by country of origin. All patients and controls were DQB1*06:02 positive and class I associations were conditioned on DQB1 alleles. Results: HLA-A*11:01 (OR = 1.49 [1.18–1.87] P = 7.0*10−4), C*04:01 (OR = 1.34 [1.10–1.63] P = 3.23*10−3), and B*35:01 (OR = 1.46 [1.13–1.89] P = 3.64*10−3) were associated with susceptibility to narcolepsy. Analysis of polymorphic class I amino-acids revealed even stronger associations with key antigen-binding residues HLA-A-Tyr9 (OR = 1.32 [1.15–1.52] P = 6.95*10−5) and HLA-C-Ser11 (OR = 1.34 [1.15–1.57] P = 2.43*10−4). Conclusions: Our findings provide a genetic basis for increased susceptibility to infectious factors or an immune cytotoxic mechanism in narcolepsy, potentially targeting hypocretin neurons. Citation: Tafti M, Lammers GJ, Dauvilliers Y, Overeem S, Mayer G, Nowak J, Pfister C, Dubois V, Eliaou JF, Eberhard HP, Liblau R, Wierzbicka A, Geisler P, Bassetti CL, Mathis J, Lecendreux M, Khatami R, Heinzer R, Haba-Rubio J, Feketeova E, Baumann CR, Kutalik Z, Tiercy JM. Narcolepsy-associated HLA class I alleles implicate cell-mediated cytotoxicity. SLEEP 2016;39(3):581–587. PMID:26518595

  6. Class III Malocclusion Surgical-Orthodontic Treatment

    National Research Council Canada - National Science Library

    Furquim, Bruna Alves; de Freitas, Karina Maria Salvatore; Janson, Guilherme; Simoneti, Luis Fernando; de Freitas, Marcos Roberto; de Freitas, Daniel Salvatore

    2014-01-01

    The aim of the present case report is to describe the orthodontic-surgical treatment of a 17-year-and-9-month-old female patient with a Class III malocclusion, poor facial esthetics, and mandibular and chin protrusion...

  7. The human amnion is a site of MHC class lb expression: Evidence for the expression of HLA-E and HLA-G

    Energy Technology Data Exchange (ETDEWEB)

    Houlihan, J.M.; Harper, H.M.; Jenkinson, H.J. [Univ. of Bristol (United Kingdom)] [and others

    1995-06-01

    The expression of HLA class I Ag by term human amnion epithelial cells was investigated. In immunostaining and FACS analysis, mAb to monomorphic class I Ag reacted extensively with amnion cells, whereas polymorphic mAb reactivity was more limited and variable. Further studies were conducted on amnion cell preparations containing negligible contaminants. Northern analysis with use of locus-specific probes demonstrated that amnion expresses two class lb genes, HLA-E and HLA-G. Radio-immunoprecipitation with use of monomorphic mAb identified two fully glycosylated cell surface class I H chains of 44 and 41 kDa; polymorphic mAbs failed to immunoprecipitate the 41-kDa product, although 44-kDa products, typical of class la Ag, were identified in some preparations. Class I H chains were isolated from amnion by affinity chromatography. Microsequencing revealed that the first nine residues of the N-terminus of the 41-kDa product aligned perfectly only with HLA-E. Overall, amnion at term appears to express class lb Ag with limited class la Ag. HLA-G is therefore expressed in two extrafetal epithelia: amnion and trophoblast. Identification of the class lb protein HLA-E-E in amnion epithelium may have implications for preterm labor that can be associated with infection of the placental membranes. 44 refs., 5 figs., 2 tabs.

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

    Directory of Open Access Journals (Sweden)

    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.

  9. Associations between HLA Class I alleles and the prevalence of nasopharyngeal carcinoma (NPC) among Tunisians

    Science.gov (United States)

    Li, Xin; Ghandri, Nahla; Piancatelli, Daniela; Adams, Sharon; Chen, Deborah; Robbins, Fu-Meei; Wang, Ena; Monaco, Alessandro; Selleri, Silvia; Bouaouina, Noureddine; Stroncek, David; Adorno, Domenico; Chouchane, Lotfi; Marincola, Francesco M

    2007-01-01

    The high prevalence of nasopharyngeal cancer (NPC) in Southern Asia and Mediterranean Northern Africa suggests genetic predisposition among other factors. While Human Leukocyte Antigen (HLA) haplotypes have been conclusively associated with NPC predisposition in Asians, Northern African Maghrebians have been less intensely studied. However, low resolution serological methods identified weak positive associations with HLA-B5, B13 and B18 and a negative with HLA-B14. Using sequence based typing (SBT), we performed a direct comparison of HLA class I frequencies in a cohort of 136 Tunisian patients with NPC matched for gender, age and geographical residence to 148 normal Tunisians. The bimodal age distribution of NPC in Maghrebians was also taken into account. HLA frequencies in normal Tunisians were also compared with those of Northern Moroccan Berbers (ME) to evaluate whether the Tunisian population in this study could be considered representative of other Maghrebian populations. HLA-B14 and -Cw08 were negatively associated with NPC (odd ratio = 0.09 and 0.18 respectively, Fisher p2-value = 0.0001 and = 0.003). Moreover, positive associations were observed for HLA-B-18, -B51 (split of -B5) and -B57 (p2-value < 0.025 in all) confirming previous findings in Maghrebs. The HLA-B14/Cw*08 haplotype frequency (HF) was 0.007 in NPC patients compared to 0.057 in both Tunisian (OR = 0.12; p2-value = 0.001) and Moroccan controls. This study confirms several previous associations noted by serologic typing between HLA class I alleles and the prevalence of NPC in Maghrebians populations. In addition, we identified a putative haplotype rare in Tunisian patients with NPC that may serve as a genetic marker for further susceptibility studies. PMID:17480220

  10. HLA class II haplotypes in Mexican systemic lupus erythematosus patients.

    Science.gov (United States)

    Cortes, Lizette M; Baltazar, Luz M; Lopez-Cardona, Maria G; Olivares, Norma; Ramos, Cesar; Salazar, Mario; Sandoval, Lucila; Lorenz, Matthias G O; Chakraborty, Ranajit; Paterson, Andrew D; Rivas, Fernando

    2004-12-01

    Systemic lupus erythematosus (SLE) is an autoimmune disease in which polymorphisms within the human leukocyte antigen (HLA) region have been associated to its etiology. For this study, HLA-DQB1, DQA1, and DRB1 genes were typed by polymerase chain reaction-sequence-specific primer in 237 individuals, taken from 74 families, who had a member with SLE, and who had their residence in the western region of Mexico; as well as in 159 ethnically matched healthy volunteers taken from 32 families. Genotype and allele frequency analysis was performed in 74 SLE patients and 54 unrelated controls. Precise three-loci identification of independent haplotypes was performed in 48 patients and 54 controls by familial segregation. Genotype distribution at each loci was concordant with Hardy-Weinberg's equilibrium in the control group. In general, no genotype effect was observed in SLE patients. Allele distribution comparison showed in the SLE group a significant increase of HLA-DQA1*0102, DQB1*0402, and DRB1*15; whereas alleles HLA-DQB1*0303 and *0501 were significantly decreased. SLE patients showed haplotype DQB1*0602-DQA1-*0102-DRB1*15 increased. As expected, patients with SLE have a reduced haplotype genetic diversity. The associations found in this study are related to an ancestral haplotype that has been observed in SLE populations of different origins.

  11. HLA class I polymorphisms are associated with development of infectious mononucleosis upon primary EBV infection

    Science.gov (United States)

    McAulay, Karen A.; Higgins, Craig D.; Macsween, Karen F.; Lake, Annette; Jarrett, Ruth F.; Robertson, Faye L.; Williams, Hilary; Crawford, Dorothy H.

    2007-01-01

    Infectious mononucleosis (IM) is an immunopathological disease caused by EBV that occurs in young adults and is a risk factor for Hodgkin lymphoma (HL). An association between EBV-positive HL and genetic markers in the HLA class I locus has been identified, indicating that genetic differences in the HLA class I locus may alter disease phenotypes associated with EBV infection. To further determine whether HLA class I alleles may affect development of EBV-associated diseases, we analyzed 2 microsatellite markers and 2 SNPs located near the HLA class I locus in patients with acute IM and in asymptomatic EBV-seropositive and -seronegative individuals. Alleles of both microsatellite markers were significantly associated with development of IM. Specific alleles of the 2 SNPs were also significantly more frequent in patients with IM than in EBV-seronegative individuals. IM patients possessing the associated microsatellite allele had fewer lymphocytes and increased neutrophils relative to IM patients lacking the allele. These patients also displayed higher EBV titers and milder IM symptoms. The results of this study indicate that HLA class I polymorphisms may predispose patients to development of IM upon primary EBV infection, suggesting that genetic variation in T cell responses can influence the nature of primary EBV infection and the level of viral persistence. PMID:17909631

  12. Autoimmune and non-autoimmune thyroid diseases have different patterns of cellular HLA class II expression

    Directory of Open Access Journals (Sweden)

    Denise Engelbrecht Zantut-Wittmann

    Full Text Available CONTEXT: Surface HLA-DR antigen is usually only expressed by antigen-presenting cells (APC. In autoimmune thyroid disease, follicle cells function as APC, thus expressing HLA-DR. However, non-autoimmune thyroid diseases may also express surface class II antigens. OBJECTIVE: To evaluate the presence and pattern of HLA class II expression in autoimmune and non-autoimmune thyroid disorders. DESIGN: Retrospective: histopathological and immunohistochemical analysis. LOCATION: Referral center, university hospital. SAMPLE: Ten histologically normal thyroids, 11 Graves’ disease, 7 Hashimoto’s thyroiditis, 10 atoxic multinodular goiter and 3 toxic adenomas were analyzed by immunohistochemistry, using a monoclonal antibody anti-HLA-DR. MAIN MEASUREMENTS: The presence of these antigens in thyroid follicular cells and their relation to inflammatory infiltrate was evaluated. The pattern of HLA-DR expression in thyroid follicular cells was analyzed: membrane, cytoplasmic or both. RESULTS: Although HLA-DR antigens were sparsely present in one of the 8 normal thyroids, in 6 of the 9 atoxic multinodular goiter and in 2 of the 3 toxic adenomas a net positivity could be seen in large areas. In all 5 Hashimoto’s thyroiditis and in 7 of the 10 Graves’ disease cases. This expression occurred in follicle cells either in contact with inflammatory cells or not. In non-autoimmune thyroid disease, HLA-DR positivity was essentially cytoplasmic, whereas in Graves’ disease and Hashimoto thyroiditis it was mainly in cell membranes. CONCLUSIONS: It is suggested that the HLA class II expression on the surface of follicle cells could be related to auto-antigen presentation to the immune system by these cells, leading to inflammation.

  13. Normal HLA class I, II, and MICA gene distribution in uveal melanoma.

    NARCIS (Netherlands)

    Metzelaar-Blok, J.A.; Hurks, H.M.; Naipal, A.; Lange, P. de; Keunen, J.E.E.; Claas, F.; Doxiadis, I.I.; Jager, M.J.

    2005-01-01

    PURPOSE: The molecules of the HLA class I and II molecules as well as the MHC class I chain-related gene A (MICA), a polymorphic and stress-induced cell surface molecule, are involved in T-cell and natural killer-cell (NK-cell) mediated immune responses. In this study we looked for any genetic

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

    Directory of Open Access Journals (Sweden)

    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.

  15. Pan-specific MHC class I predictors: A benchmark of HLA class I pan-specific prediction methods

    DEFF Research Database (Denmark)

    Zhang, Hao; Lundegaard, Claus; Nielsen, Morten

    2009-01-01

    emerging pathogens. Methods have recently been published that are able to predict peptide binding to any human MHC class I molecule. In contrast to conventional allele-specific methods, these methods do allow for extrapolation to un-characterized MHC molecules. These pan-specific HLA predictors have...... not previously been compared using independent evaluation sets. Results: A diverse set of quantitative peptide binding affinity measurements was collected from IEDB, together with a large set of HLA class I ligands from the SYFPEITHI database. Based on these data sets, three different pan-specific HLA web......-accessible predictors NetMHCpan, Adaptive-Double-Threading (ADT), and KISS were evaluated. The performance of the pan-specific predictors was also compared to a well performing allele-specific MHC class I predictor, NetMHC, as well as a consensus approach integrating the predictions from the NetMHC and Net...

  16. Early cephalometric characteristics in Class III malocclusion

    OpenAIRE

    Farias,Vanessa Costa; Tesch,Ricardo de Souza; Denardin,Odilon Victor Porto; Ursi,Weber

    2012-01-01

    OBJECTIVE: Early identification of craniofacial morphological characteristics allows orthopedic segmented interventions to attenuate dentoskeletal discrepancies, which may be partially disguised by natural dental compensation. To investigate the morphological characteristics of Brazilian children with Class III malocclusion, in stages I and II of cervical vertebrae maturation and compare them with the characteristics of Class I control patients. METHODS: Pre-orthodontic treatment records of 2...

  17. Treatment planning in Class III malocclusion.

    Science.gov (United States)

    McIntyre, Grant T

    2004-01-01

    In Class III malocclusion, the overjet is reduced and may be reversed, with one or more incisor teeth in lingual crossbite. In the early mixed dentition, and in older patients with mild skeletal discrepancies, orthodontic treatment usually involves proclining the maxilliary anterior teeth into positive overjet. When the permanent dentition has established, orthodontic therapy is usually aimed at compensating for the underlying mild-moderate Class III skeletal discrepancy by proclining and retroclining the maxillary and mandibular incisors, respectively. In contrast, adolescent and non-growing patients with severe Class III skeletal discrepancies require a combination of orthodontic treatment and orthognathic surgery to correct the underlying skeletal pattern. Adolescent patients with moderately severe skeletal discrepancies require careful treatment planning because they are often at the limits of orthodontic compensation, and further mandibular growth may prevent a stable Class I occlusion from being maintained with growth. In this situation, treatment should be limited to aligning the maxillary arch, accepting that orthognathic surgery will be required to correct the underlying Class III skeletal discrepancy when skeletal growth has been completed. This article will inform dental professionals about the aetiology, assessment, diagnosis and treatment of patients with Class III malocclusions. Specifically, the types of orthodontic treatment that can be completed at the various stages of dental development and skeletal growth will be discussed.

  18. HLA Class I and II study in a mestizo family with high incidence of autoimmune disease.

    Science.gov (United States)

    de Sorrentino, Alicia Habegger; Young, Marcela; Marinic, Karina; Motta, Patricia Fabiana; Baruzzo, Carlos

    2013-01-01

    There are many factors that influence the pathogenesis of autoimmune disease of which host genetic factors play an important role. The aim of this study was to investigate the HLA Class I and II genes in a family with a high incidence of AID to establish whether they contribute to the development of these disease. Four of them had been diagnosed with SLE and one with AHA. The patients with SLE showed the presence of HLA-A*02 B*40 DRB1*04:07 DQB1*03:02 haplotype with a high statistical significance. This haplotype was not present in the healthy individuals and in the patient with AHA, although the DRB1*04:07 DQB1*03:02 haplotype (carried by both parents) was found in the AHA patients and one of the healthy individuals. We must consider how HLA Class I in linkage disequilibrium with HLA Class II may be involved in susceptibility or in the development of SLE. An extensive study in this population should be conducted to establish the true participation of the HLA Class I region. Copyright © 2012 Elsevier España, S.L. All rights reserved.

  19. HLA class II gene associations in African American Type 1 diabetes reveal a protective HLA-DRB1*03 haplotype

    Science.gov (United States)

    Howson, J M M; Roy, M S; Zeitels, L; Stevens, H; Todd, J A

    2013-01-01

    Aims Owing to strong linkage disequilibrium between markers, pinpointing disease associations within genetic regions is difficult in European ancestral populations, most notably the very strong association of the HLA-DRB1*03-DQA1*05:01-DQB1*02:01 haplotype with Type 1 diabetes risk, which is assumed to be because of a combination of HLA-DRB1 and HLA-DQB1. In contrast, populations of African ancestry have greater haplotype diversity, offering the possibility of narrowing down regions and strengthening support for a particular gene in a region being causal. We aimed to study the human leukocyte antigen (HLA) region in African American Type 1 diabetes. Methods Two hundred and twenty-seven African American patients with Type 1 diabetes and 471 African American control subjects were tested for association at the HLA class II genes, HLA-DRB1, HLA-DQA1, HLA-DQB1 and 5147 single nucleotide polymorphisms across the major histocompatibility complex region using logistic regression models. Population admixture was accounted for with principal components analysis. Results Single nucleotide polymorphism marker associations were explained by the HLA associations, with the major peak over the class II loci. The HLA association overall was extremely strong, as expected for Type 1 diabetes, even in African Americans in whom diabetes diagnosis is heterogeneous. In addition, there were unique features: the HLA-DRB1*03 haplotype was split into HLA-DRB1*03:01, which confers greatest susceptibility in these samples (odds ratio 3.17, 95% CI 1.72–5.83) and HLA-DRB1*03:02, an allele rarely observed in Europeans, which confers the greatest protection in these African American samples (odds ratio 0.22, 95% CI 0.09–0.55). Conclusions The unique diversity of the African HLA region we have uncovered supports a specific and major role for HLA-DRB1 in HLA-DRB1*03 haplotype-associated Type 1 diabetes risk. PMID:23398374

  20. Early cephalometric characteristics in Class III malocclusion

    Directory of Open Access Journals (Sweden)

    Vanessa Costa Farias

    2012-04-01

    Full Text Available OBJECTIVE: Early identification of craniofacial morphological characteristics allows orthopedic segmented interventions to attenuate dentoskeletal discrepancies, which may be partially disguised by natural dental compensation. To investigate the morphological characteristics of Brazilian children with Class III malocclusion, in stages I and II of cervical vertebrae maturation and compare them with the characteristics of Class I control patients. METHODS: Pre-orthodontic treatment records of 20 patients with Class III malocclusion and 20 control Class I patients, matched by the same skeletal maturity index and sex, were selected. The craniofacial structures and their relationships were divided into different categories for analysis. Angular and linear measures were adopted from the analyses previously described by Downs, Jarabak, Jacobson and McNamara. The differences found between the groups of Class III patients and Class I control group, both subdivided according to the stage of cervical vertebrae maturation (I or II, were assessed by analysis of variance (ANOVA, complemented by Bonferroni's multiple mean comparisons test. RESULTS: The analysis of variance showed statistically significant differences in the different studied groups, between the mean values found for some angular (SNA, SNB, ANB and linear variables (Co - Gn, N - Perp Pog, Go - Me, Wits, S - Go, Ar - Go. CONCLUSION: Assessed children displaying Class III malocclusion show normal anterior base of skull and maxilla, and anterior positioning of the mandible partially related to increased posterior facial height with consequent mandibular counterclockwise rotation.

  1. Involvement of HLA class I molecules in the immune escape of urologic tumors.

    Science.gov (United States)

    Carretero, R; Gil-Julio, H; Vázquez-Alonso, F; Garrido, F; Castiñeiras, J; Cózar, J M

    2014-04-01

    To analyze the influence of different alterations in human leukocyte antigen class I molecules (HLA I) in renal cell carcinoma, as well as in bladder and prostate cancer. We also study the correlation between HLA I expression and the progression of the disease and the response after immunotherapy protocols. It has been shown, experimentally, that the immune system can recognize and kill neoplastic cells. By analyzing the expression of HLA I molecules on the surface of cancer cells, we were able to study the tumor escape mechanisms against the immune system. Alteration or irreversible damage in HLA I molecules is used by the neoplastic cells to escape the immune system. The function of these molecules is to recognize endogenous peptides and present them to T cells of the immune system. There is a clear relationship between HLA I reversible alterations and success of therapy. Irreversible lesions also imply a lack of response to treatment. The immune system activation can reverse HLA I molecules expression in tumors with reversible lesions, whereas tumors with irreversible ones do not respond to such activation. Determine the type of altered HLA I molecules in tumors is of paramount importance when choosing the type of treatment to keep looking for therapeutic success. Those tumors with reversible lesions can be treated with traditional immunotherapy; however, tumour with irreversible alterations should follow alternative protocols, such as the use of viral vectors carrying the HLA genes to achieve damaged re-expression of the protein. From studies in urologic tumors, we can conclude that the HLA I molecules play a key role in these tumors escape to the immune system. Copyright © 2013 AEU. Published by Elsevier Espana. All rights reserved.

  2. Identification of class I HLA T cell control epitopes for West Nile virus.

    Directory of Open Access Journals (Sweden)

    Saghar Kaabinejadian

    Full Text Available The recent West Nile virus (WNV outbreak in the United States underscores the importance of understanding human immune responses to this pathogen. Via the presentation of viral peptide ligands at the cell surface, class I HLA mediate the T cell recognition and killing of WNV infected cells. At this time, there are two key unknowns in regards to understanding protective T cell immunity: 1 the number of viral ligands presented by the HLA of infected cells, and 2 the distribution of T cell responses to these available HLA/viral complexes. Here, comparative mass spectroscopy was applied to determine the number of WNV peptides presented by the HLA-A*11:01 of infected cells after which T cell responses to these HLA/WNV complexes were assessed. Six viral peptides derived from capsid, NS3, NS4b, and NS5 were presented. When T cells from infected individuals were tested for reactivity to these six viral ligands, polyfunctional T cells were focused on the GTL9 WNV capsid peptide, ligands from NS3, NS4b, and NS5 were less immunogenic, and two ligands were largely inert, demonstrating that class I HLA reduce the WNV polyprotein to a handful of immune targets and that polyfunctional T cells recognize infections by zeroing in on particular HLA/WNV epitopes. Such dominant HLA/peptide epitopes are poised to drive the development of WNV vaccines that elicit protective T cells as well as providing key antigens for immunoassays that establish correlates of viral immunity.

  3. The principal genetic determinants for nasopharyngeal carcinoma in China involve the HLA class I antigen recognition groove.

    Directory of Open Access Journals (Sweden)

    Minzhong Tang

    Full Text Available Nasopharyngeal carcinoma (NPC is an epithelial malignancy facilitated by Epstein-Barr Virus infection. Here we resolve the major genetic influences for NPC incidence using a genome-wide association study (GWAS, independent cohort replication, and high-resolution molecular HLA class I gene typing including 4,055 study participants from the Guangxi Zhuang Autonomous Region and Guangdong province of southern China. We detect and replicate strong association signals involving SNPs, HLA alleles, and amino acid (aa variants across the major histocompatibility complex-HLA-A, HLA -B, and HLA -C class I genes (P(HLA-A-aa-site-62 = 7.4 × 10(-29; P (HLA-B-aa-site-116 = 6.5 × 10(-19; P (HLA-C-aa-site-156 = 6.8 × 10(-8 respectively. Over 250 NPC-HLA associated variants within HLA were analyzed in concert to resolve separate and largely independent HLA-A, -B, and -C gene influences. Multivariate logistical regression analysis collapsed significant associations in adjacent genes spanning 500 kb (OR2H1, GABBR1, HLA-F, and HCG9 as proxies for peptide binding motifs carried by HLA- A*11:01. A similar analysis resolved an independent association signal driven by HLA-B*13:01, B*38:02, and B*55:02 alleles together. NPC resistance alleles carrying the strongly associated amino acid variants implicate specific class I peptide recognition motifs in HLA-A and -B peptide binding groove as conferring strong genetic influence on the development of NPC in China.

  4. Generation of a Novel HLA Class I Transgenic Mouse Model Carrying a Knock-in Mutation at the β2-Microglobulin Locus.

    Science.gov (United States)

    Harada, Naomoto; Fukaya, Satoshi; Wada, Hiroshi; Goto, Risa; Osada, Toshihiro; Gomori, Akira; Ikizawa, Koichi; Sakuragi, Motomu; Oda, Nobuyuki

    2017-01-01

    We generated a series of monochain HLA class I knock-in (KI) mouse strains, in which a chimeric HLA class I molecule (α1/α2 domain of HLA-A*0201, HLA-A*0301, HLA-A*2402, or HLA-A*3101 and α3 domain of H-2D(b)) was covalently linked with 15 aa to human β2-microglobulin (β2m) and introduced into the endogenous mouse β2m locus. In homozygous KI mice, mouse β2m gene disruption resulted in loss of the endogenous H-2 class I molecules and reduction in the peripheral CD8(+) T cell population that was partially restored by monochain HLA class I expression. A gene dosage-dependent expression of HLA, similar to that in human PBMCs, was detected in heterozygous and homozygous HLA KI mice. Upon vaccination with various virus epitopes, HLA-restricted, epitope-specific CTLs were induced in HLA KI mice, similar to the response in the commonly used HLA transgenic mice. Importantly, the CTL responses induced in heterozygous KI mice were similar to those in homozygous KI mice. These results suggest that coexpression of H-2 class I does not affect HLA-restricted CTL responses in HLA KI mice, which differs from the situation reported for monochain HLA Tg × β2m(-/-) mice. Furthermore, we generated double KI mice harboring two different HLA (HLA-A*2402 and HLA-A*0301) KI alleles, which showed a CTL response against both HLA-A24 and HLA-A3 epitopes when immunized with a mixture of both peptides. These results indicated that this HLA class I KI mouse model provides powerful research tools not only for the study of HLA class I-restricted CTL responses, but also for preclinical vaccine evaluation. Copyright © 2016 by The American Association of Immunologists, Inc.

  5. Signal transduction by HLA class II antigens expressed on activated T cells

    DEFF Research Database (Denmark)

    Ødum, Niels; Martin, P J; Schieven, G L

    1991-01-01

    Human T cells express HLA class II antigens upon activation. Although activated, class II+ T cells can present alloantigens under certain circumstances, the functional role of class II antigens on activated T cells remains largely unknown. Here, we report that cross-linking of HLA-DR molecules...... after cross-linking CD4. Ligation of CD4 and class II molecules generated a synergistic effect of the intracellular free Ca2+ concentration response that required an interaction between the molecules on the cell surface. Since class II is the natural ligand for CD4, the present data suggest that class...... expressed on allospecific, CD4+ T clones and cell lines can function as transduction elements that trigger rapid cellular responses including tyrosine phosphorylation of cellular proteins and mobilization of Ca2+ from internal stores. The proteins phosphorylated on tyrosine were distinct from those observed...

  6. 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...... biliary cirrhosis (PBC) and in healthy Danes. The following genetic markers were found with increased frequencies in PBC: HLA-B8 (relative risk, RR = 2.4, P less than 0.05, 'corrected' P greater than 0.05), HLA-DR3 (RR = 3.4, P less than 0.01, 'corrected' P less than 0.05), the DRB3*01/02/03 (DRw52...

  7. High-throughput high-resolution class I HLA genotyping in East Africa.

    Directory of Open Access Journals (Sweden)

    Rebecca N Koehler

    Full Text Available HLA, the most genetically diverse loci in the human genome, play a crucial role in host-pathogen interaction by mediating innate and adaptive cellular immune responses. A vast number of infectious diseases affect East Africa, including HIV/AIDS, malaria, and tuberculosis, but the HLA genetic diversity in this region remains incompletely described. This is a major obstacle for the design and evaluation of preventive vaccines. Available HLA typing techniques, that provide the 4-digit level resolution needed to interpret immune responses, lack sufficient throughput for large immunoepidemiological studies. Here we present a novel HLA typing assay bridging the gap between high resolution and high throughput. The assay is based on real-time PCR using sequence-specific primers (SSP and can genotype carriers of the 49 most common East African class I HLA-A, -B, and -C alleles, at the 4-digit level. Using a validation panel of 175 samples from Kampala, Uganda, previously defined by sequence-based typing, the new assay performed with 100% sensitivity and specificity. The assay was also implemented to define the HLA genetic complexity of a previously uncharacterized Tanzanian population, demonstrating its inclusion in the major East African genetic cluster. The availability of genotyping tools with this capacity will be extremely useful in the identification of correlates of immune protection and the evaluation of candidate vaccine efficacy.

  8. Angiotensinogen and HLA class II predict bevacizumab response in recurrent glioblastoma patients

    DEFF Research Database (Denmark)

    Urup, Thomas; Michaelsen, Signe Regner; Olsen, Lars Rønn

    2016-01-01

    .0009) and high expression of a HLA class II gene (2-fold increase in HLA-DQA1; OR = 1.22; 95% CI: 1.01-1.47; P = 0.04). These two genes were included in a model that is able predict response to bevacizumab combination therapy in clinical practice. When stratified for a validated prognostic index, the predictive...... model for response was significantly associated with improved overall survival. Conclusion: Two genes (low angiotensinogen and high HLA-class II expression) were predictive for bevacizumab response and were included in a predictive model for response. This model can be used in clinical practice...... for bevacizumab response in recurrent glioblastoma patients. Methods: The study included a total of 82 recurrent glioblastoma patients treated with bevacizumab combination therapy whom were both response and biomarker evaluable. Gene expression of tumor tissue was analyzed by using a customized Nano...

  9. The Cancer Exome Generated by Alternative mRNA Splicing Dilutes Predicted HLA Class I Epitope Density

    DEFF Research Database (Denmark)

    Stranzl, Thomas; Larsen, Mette Voldby; Lund, Ole

    2012-01-01

    is frequently observed in various types of cancer. Down-regulation of genes related to HLA class I antigen processing has been observed in several cancer types, leading to fewer HLA class I antigens on the cell surface. Here, we use a peptidome wide analysis of predicted alternative splice forms, based......Several studies have shown that cancers actively regulate alternative splicing. Altered splicing mechanisms in cancer lead to cancer-specific transcripts different from the pool of transcripts occurring only in healthy tissue. At the same time, altered presentation of HLA class I epitopes...... on a publicly available database, to show that peptides over-represented in cancer splice variants comprise significantly fewer predicted HLA class I epitopes compared to peptides from normal transcripts. Peptides over-represented in cancer transcripts are in the case of the three most common HLA class I...

  10. HLA class II allele polymorphism in an outbreak of chikungunya fever in Middle Andaman, India.

    Science.gov (United States)

    Chaaithanya, Itta Krishna; Muruganandam, Nagarajan; Anwesh, Maile; Rajesh, Reesu; Ghosal, Sruti R; Kartick, Chinnaiah; Prasad, Kadiyala Nageswara; Muthumani, Karuppiah; Vijayachari, Paluru

    2013-10-01

    A sudden upsurge of fever cases with joint pain was observed in the outpatient department, Community Health Centre, Rangat during July-August 2010 in Rangat Middle Andaman, India. The aetiological agent responsible for the outbreak was identified as chikungunya virus (CHIKV), by using RT-PCR and IgM ELISA. The study investigated the association of polymorphisms in the human leucocyte antigen class II genes with susceptibility or protection against CHIKV. One hundred and one patients with clinical features suggestive of CHIKV infection and 104 healthy subjects were included in the study. DNA was extracted and typed for HLA-DRB1 and DQB1 alleles. Based on the amino acid sequences of HLA-DQB1 retrieved from the IMGT/HLA database, critical amino acid differences in the specific peptide-binding pockets of HLA-DQB1 molecules were investigated. The frequencies of HLA-DRB1 alleles were not significantly different, whereas lower frequency of HLA-DQB1*03:03 was observed in CHIKV patients compared with the control population [P = 0·001, corrected P = 0·024; odds ratio (OR)  = 0, 95% confidence interval (95% CI) 0·0-0·331; Peto's OR = 0·1317, 95% CI 0·0428-0·405). Significantly lower frequency of glutamic acid at position 86 of peptide-binding pocket 1 coding HLA-DQB1 genotypes was observed in CHIKV patients compared with healthy controls (P = 0·004, OR = 0·307, 95% CI 0·125-0·707). Computational binding predictions of CD4 epitopes of CHIKV by NetMHCII revealed that HLA-DQ molecules are known to bind more CHIKV peptides than HLA-DRB1 molecules. The results suggest that HLA-DQB1 alleles and critical amino acid differences in the peptide-binding pockets of HLA-DQB1 alleles might have role in influencing infection and pathogenesis of CHIKV. © 2013 John Wiley & Sons Ltd.

  11. Ectopic expression of HLA-DO in mouse dendritic cells diminishes MHC class II antigen presentation.

    Science.gov (United States)

    Fallas, Jennifer L; Tobin, Helen M; Lou, Olivia; Guo, Donglin; Sant'Angelo, Derek B; Denzin, Lisa K

    2004-08-01

    The MHC class II-like molecule HLA-DM (DM) (H-2M in mice) catalyzes the exchange of CLIP for antigenic peptides in the endosomes of APCs. HLA-DO (DO) (H-2O in mice) is another class II-like molecule that is expressed in B cells, but not in other APCs. Studies have shown that DO impairs or modifies the peptide exchange activity of DM. To further evaluate the role of DO in Ag processing and presentation, we generated transgenic mice that expressed the human HLA-DOA and HLA-DOB genes under the control of a dendritic cell (DC)-specific promoter. Our analyses of DCs from these mice showed that as DO levels increased, cell surface levels of A(b)-CLIP also increased while class II-peptide levels decreased. The presentation of some, but not all, exogenous Ags to T cells or T hybridomas was significantly inhibited by DO. Surprisingly, H-2M accumulated in DO-expressing DCs and B cells, suggesting that H-2O/DO prolongs the half-life of H-2M. Overall, our studies showed that DO expression impaired H-2M function, resulting in Ag-specific down-modulation of class II Ag processing and presentation.

  12. Defining the HLA class I-associated viral antigen repertoire from HIV-1-infected human cells

    DEFF Research Database (Denmark)

    Ternette, Nicola; Yang, Hongbing; Partridge, Thomas

    2016-01-01

    Recognition and eradication of infected cells by cytotoxic T lymphocytes is a key defense mechanism against intracellular pathogens. High-throughput definition of HLA class I-associated immunopeptidomes by mass spectrometry is an increasingly important analytical tool to advance our understanding...

  13. Class III Malocclusion Surgical-Orthodontic Treatment

    National Research Council Canada - National Science Library

    Furquim, Bruna Alves; de Freitas, Karina Maria Salvatore; Janson, Guilherme; Simoneti, Luis Fernando; de Freitas, Marcos Roberto; de Freitas, Daniel Salvatore

    2014-01-01

      The aim of the present case report is to describe the orthodontic-surgical treatment of a 17-year-and-9-month-old female patient with a Class III malocclusion, poor facial esthetics, and mandibular and chin protrusion...

  14. Genetic and epigenetic control of the major histocompatibility complex class Ib gene HLA-G in trophoblast cell lines.

    Science.gov (United States)

    Holling, Tjadine M; Bergevoet, Marloes W T; Wierda, Rutger J; van Eggermond, Marja C J A; van den Elsen, Peter J

    2009-09-01

    The transcriptional regulation of the major histocompatibility complex class (MHC) Ib gene HLA-G differs from the classical MHC class I genes. The cis-acting regulatory elements typical for classical MHC class I promoters are divergent in the promoter of HLA-G, rendering this gene unresponsive to NF-kappaB, IRF-1, and class II transactivator (CIITA)-mediated activation pathways. However, as we have previously shown, transactivation of HLA-G is regulated by CREB-1. Because CREB-1 is ubiquitously expressed, this observation does not explain the tissue-restricted expression of HLA-G in extravillous cytotrophoblasts. Using HLA-G-expressing JEG-3 cells and HLA-G-deficient JAR trophoblast-derived choriocarcinoma cells as a model, we have investigated the contribution of DNA methylation and histone acetylation in the transcriptional activation of HLA-G. Despite similar levels of DNA methylation both in JEG3 and JAR cells, we found the levels of histone acetylation in HLA-G promoter chromatin to be significantly enhanced in JEG3 cells coinciding with HLA-G expression.

  15. Shared peptide binding of HLA Class I and II alleles associate with cutaneous nevirapine hypersensitivity and identify novel risk alleles

    DEFF Research Database (Denmark)

    Pavlos, Rebecca; McKinnon, Elizabeth J.; Ostrov, David A.

    2017-01-01

    Genes of the human leukocyte antigen (HLA) system encode cell-surface proteins involved in regulation of immune responses, and the way drugs interact with the HLA peptide binding groove is important in the immunopathogenesis of T-cell mediated drug hypersensitivity syndromes. Nevirapine (NVP......), is an HIV-1 antiretroviral with treatment-limiting hypersensitivity reactions (HSRs) associated with multiple class I and II HLA alleles. Here we utilize a novel analytical approach to explore these multi-allelic associations by systematically examining HLA molecules for similarities in peptide binding...... specificities and binding pocket structure. We demonstrate that primary predisposition to cutaneous NVP HSR, seen across ancestral groups, can be attributed to a cluster of HLA-C alleles sharing a common binding groove F pocket with HLA-C*04:01. An independent association with a group of class II alleles which...

  16. Association of HLA class II alleles and CTLA-4 polymorphism with type 1 diabetes

    Directory of Open Access Journals (Sweden)

    Rana J EI Wafai

    2011-01-01

    Full Text Available Type-1 diabetes mellitus (T1DM is a progressive complex autoimmune disease in which combinations of environmental as well as genetic factors contribute to T-cell mediated destruction of insulin-secreting β-cells of the pancreas. HLA class II alleles on chromosome 6p21 [insulin dependent diabetes mellitus 1 (IDDM1], especially DR and DQ, show strong association with T1DM. In addition, several studies have suggested that polymorphisms in the CTLA-4 gene (IDDM12 on chromosome 2q33 form part of the genetic susceptibility for type 1 diabetes. The aim of this study was to analyze HLA alleles of the DQB1 and DRB1 genes using polymerase chain reaction using sequence specific primers (PCR-SSP technique and to investigate the asso-ciation of the A49G CTLA-4 polymorphism using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP analysis in Lebanese T1DM patients. The study was conduc-ted on 39 Lebanese T1DM patients. Results of HLA typing showed an increased frequency of the HLA-DQB1FNx010201, HLA-DQB1FNx010302, HLA-DRB1FNx010301 and HLA-DRB1FNx010401 alleles, sugges-ting risk association and thus can be considered as susceptibility alleles. On the other hand, strong protection against the disease was conferred by the HLA-DRB1FNx01110101, HLA-DQB1FNx010301 and HLADQB1FNx010601 alleles. RFLP analysis of the A49G polymorphism showed a significant increase in the G allele and GG genotype frequencies in patients, suggesting that CTLA-4 may be considered as a susceptibility gene for the development of T1DM in the Lebanese population. Analysis of the two polymorphisms showed no detectable association between the two genes. However, a significant negative association of the G allele with the DQB1FNx010201 allele was ob-served. This might indicate that the two genetic risk factors, namely HLA and CTLA-4, act independently of each other with no additive effect.

  17. Inhibition of HLA-DM Mediated MHC Class II Peptide Loading by HLA-DO Promotes Self Tolerance.

    Science.gov (United States)

    Denzin, Lisa K

    2013-12-17

    Major histocompatibility class II (MHCII) molecules are loaded with peptides derived from foreign and self-proteins within the endosomes and lysosomes of antigen presenting cells (APCs). This process is mediated by interaction of MHCII with the conserved, non-polymorphic MHCII like molecule HLA-DM (DM). DM activity is directly opposed by HLA-DO (DO), another conserved, non-polymorphic MHCII like molecule. DO is an MHCII substrate mimic. Binding of DO to DM prevents MHCII from binding to DM, thereby inhibiting peptide loading. Inhibition of DM function enables low stability MHC complexes to survive and populate the surface of APCs. As a consequence, DO promotes the display of a broader pool of low abundance self-peptides. Broadening the peptide repertoire theoretically reduces the likelihood of inadvertently acquiring a density of self-ligands that is sufficient to activate self-reactive T cells. One function of DO, therefore, is to promote T cell tolerance by shaping the visible image of self. Recent data also shows that DO influences the adaptive immune response by controlling B cell entry into the germinal center reaction. This review explores the data supporting these concepts.

  18. Inhibition of HLA-DM mediated MHC class II peptide loading by HLA-DO promotes self tolerance

    Directory of Open Access Journals (Sweden)

    Lisa K. Denzin

    2013-12-01

    Full Text Available Major histocompatibility class II (MHCII molecules are loaded with peptides derived from foreign and self-proteins within the endosomes and lysosomes of antigen presenting cells (APCs. This process is mediated by interaction of MHCII with the conserved, nonpolymorphic MHCII-like molecule HLA-DM (DM. DM activity is directly opposed by HLA-DO (DO, another conserved, non-polymorphic MHCII like molecule. DO is an MHCII substrate mimic. Binding of DO to DM prevents MHCII from binding to DM, thereby inhibiting peptide loading. Inhibition of DM function enables low stability MHC complexes to survive and populate the surface of APCS. As a consequence, DO promotes the display of a broader pool of low abundance self-peptides. Broadening the peptide repertoire theoretically reduces the likelihood of inadvertently acquiring a density of self-ligands that is sufficient to activate self-reactive T cells. One function of DO, therefore, is to promote T cell tolerance by shaping the visible image of self. Recent data also shows that DO influences the adaptive immune response by controlling B cell entry into the germinal center reaction. This review explores the data supporting these concepts.

  19. Next-generation sequencing for HLA typing of class I loci

    Directory of Open Access Journals (Sweden)

    Carrington Mary

    2011-01-01

    Full Text Available Abstract Background Comprehensive sequence characterization across the MHC is important for successful organ transplantation and genetic association studies. To this end, we have developed an automated sample preparation, molecular barcoding and multiplexing protocol for the amplification and sequence-determination of class I HLA loci. We have coupled this process to a novel HLA calling algorithm to determine the most likely pair of alleles at each locus. Results We have benchmarked our protocol with 270 HapMap individuals from four worldwide populations with 96.4% accuracy at 4-digit resolution. A variation of this initial protocol, more suitable for large sample sizes, in which molecular barcodes are added during PCR rather than library construction, was tested on 95 HapMap individuals with 98.6% accuracy at 4-digit resolution. Conclusions Next-generation sequencing on the 454 FLX Titanium platform is a reliable, efficient, and scalable technology for HLA typing.

  20. HLA Class I and Class II Conserved Extended Haplotypes and Their Fragments or Blocks in Mexicans: Implications for the Study of Genetic Diversity in Admixed Populations

    Science.gov (United States)

    Ohashi, Marina; Lebedeva, Tatiana; Acuña-Alonzo, Víctor; Yunis, María; Granados-Montiel, Julio; Cruz-Lagunas, Alfredo; Vargas-Alarcón, Gilberto; Rodríguez-Reyna, Tatiana S.; Fernandez-Viña, Marcelo; Granados, Julio; Yunis, Edmond J.

    2013-01-01

    Major histocompatibility complex (MHC) genes are highly polymorphic and informative in disease association, transplantation, and population genetics studies with particular importance in the understanding of human population diversity and evolution. The aim of this study was to describe the HLA diversity in Mexican admixed individuals. We studied the polymorphism of MHC class I (HLA-A, -B, -C), and class II (HLA-DRB1, -DQB1) genes using high-resolution sequence based typing (SBT) method and we structured the blocks and conserved extended haplotypes (CEHs) in 234 non-related admixed Mexican individuals (468 haplotypes) by a maximum likelihood method. We found that HLA blocks and CEHs are primarily from Amerindian and Caucasian origin, with smaller participation of African and recent Asian ancestry, demonstrating a great diversity of HLA blocks and CEHs in Mexicans from the central area of Mexico. We also analyzed the degree of admixture in this group using short tandem repeats (STRs) and HLA-B that correlated with the frequency of most probable ancestral HLA-C/−B and -DRB1/−DQB1 blocks and CEHs. Our results contribute to the analysis of the diversity and ancestral contribution of HLA class I and HLA class II alleles and haplotypes of Mexican admixed individuals from Mexico City. This work will help as a reference to improve future studies in Mexicans regarding allotransplantation, immune responses and disease associations. PMID:24086347

  1. The Escape of Cancer from T Cell-Mediated Immune Surveillance: HLA Class I Loss and Tumor Tissue Architecture

    Directory of Open Access Journals (Sweden)

    Federico Garrido

    2017-02-01

    Full Text Available Tumor immune escape is associated with the loss of tumor HLA class I (HLA-I expression commonly found in malignant cells. Accumulating evidence suggests that the efficacy of immunotherapy depends on the expression levels of HLA class I molecules on tumors cells. It also depends on the molecular mechanism underlying the loss of HLA expression, which could be reversible/“soft” or irreversible/“hard” due to genetic alterations in HLA, β2-microglobulin or IFN genes. Immune selection of HLA-I negative tumor cells harboring structural/irreversible alterations has been demonstrated after immunotherapy in cancer patients and in experimental cancer models. Here, we summarize recent findings indicating that tumor HLA-I loss also correlates with a reduced intra-tumor T cell infiltration and with a specific reorganization of tumor tissue. T cell immune selection of HLA-I negative tumors results in a clear separation between the stroma and the tumor parenchyma with leucocytes, macrophages and other mononuclear cells restrained outside the tumor mass. Better understanding of the structural and functional changes taking place in the tumor microenvironment may help to overcome cancer immune escape and improve the efficacy of different immunotherapeutic strategies. We also underline the urgent need for designing strategies to enhance tumor HLA class I expression that could improve tumor rejection by cytotoxic T-lymphocytes (CTL.

  2. KIR genes and HLA class I ligands in a Caucasian Brazilian population with colorectal cancer.

    Science.gov (United States)

    Portela, Pâmela; Merzoni, Joice; Lindenau, Juliana D; Damin, Daniel C; Wilson, Timothy John; Roesler, Rafael; Schwartsmann, Gilberto; Jobim, Luiz Fernando; Jobim, Mariana

    2017-03-01

    Colorectal cancer (CRC) can occur anywhere in the colon or rectum and represents the third most common cancer in the world in both sexes. Natural killer cells (NK) are part of the innate immune system recognizing class I HLA molecules on target cells through their membrane receptors, called killer cell immunoglobulin-like receptors (KIR). The aim of our study was to evaluate the association between the KIR genes and HLA ligands in patients with colorectal cancer and healthy controls. We examined the polymorphism of 16 KIR genes and their HLA ligands in 154 caucasoid CRC patients and 216 controls. When both groups were compared, no significant differences were found for HLA ligands and KIR genes after Bonferroni correction. However, the Bx haplotypes (heterozygous and homozygous for the haplotype B) were more frequent in controls, when compared with patients. These findings suggest that individuals with Bx haplotypes could have some protection to colorectal cancer. The hypothesis is not related with the presence of a special KIR gene and HLA ligand related to the disease, but to the presence of several activating genes in the individuals with no better action of one in relation to other. Further studies to confirm this observation are warranted. Copyright © 2017. Published by Elsevier Inc.

  3. Polymorphisms of HLA Class I and II Alleles in Iraqi Patients with Hepatic Hydatid Infection

    Directory of Open Access Journals (Sweden)

    Al-Ghurabi Batool H

    2017-04-01

    Full Text Available Background: Hepatic hydatid disease (HHD is a parasitic zoonosis caused by larval stage of Echinococcus tape worm. In addition to environmental factors, genetic constitution of hosts seems to play a crucial role in acquiring the infection and developing disease. Aims: This study was carried out to investigate the association of HLA-class I and class II (A, B, DR and DQ alleles with HHD by genotyping in Iraqi patients, as well as to provide information about genotypes that confer susceptibility or resistance to develop the disease. Materials and Methods: Twenty patients with HHD, their age range (20-50 years and 20 healthy controls their ages were matched with the patients were enrolled in this study. Blood was collected from patients and controls, DNA was extracted from blood samples, and then HLA-class I and class II genotyping was performed by polymerase chain reaction-sequence specific oligonucleotide probes (PCR-SSO. Results: The present findings showed that frequencies of HLA-A*32 (65%; P=0.011, DRB1*11 (60%; P=0.004 and DQB1*03 (70%; P=0.007 alleles are significantly higher in patients than controls, while the frequency of DRB1*04 was significantly decreased in patients when compared to controls (25% vs. 75%; P=0.002. Furthermore, the current study could not observe significant differences in the frequencies of HLA-B alleles between patients and controls. Conclusions: We concluded that HLA-A*32, DRB1*11 and DQB1*03 alleles might contribute to the increased susceptibility to HHD and DRB1*04 could be a protective marker against the disease.

  4. MHC class II super-enhancer increases surface expression of HLA-DR and HLA-DQ and affects cytokine production in autoimmune vitiligo

    NARCIS (Netherlands)

    Cavalli, G.; Hayashi, M.; Jin, Y.; Yorgov, D.; Santorico, S.A.; Holcomb, C.; Rastrou, M.; Erlich, H.; Tengesdal, I.W.; Dagna, L.; Neff, C.P.; Palmer, B.E.; Spritz, R.A.; Dinarello, C.A.

    2016-01-01

    Genetic risk for autoimmunity in HLA genes is most often attributed to structural specificity resulting in presentation of self-antigens. Autoimmune vitiligo is strongly associated with the MHC class II region. Here, we fine-map vitiligo MHC class II genetic risk to three SNPs only 47 bp apart,

  5. HLA-DM induces CLIP dissociation from MHC class II alpha beta dimers and facilitates peptide loading.

    Science.gov (United States)

    Denzin, L K; Cresswell, P

    1995-07-14

    Human leukocyte antigen DM (HLA-DM) molecules are structurally related to classical MHC class II molecules and reside in the lysosome-like compartment where class II-restricted antigen processing is thought to occur. Mutant cell lines lacking HLA-DM are defective in antigen processing and accumulate class II molecules associated with a nested set of invariant chain-derived peptides (class II-associated invariant chain peptides, CLIP). Here we show that HLA-DM catalyzes the dissociation of CLIP from MHC class II-CLIP complexes in vitro and facilitates the binding of antigenic peptides. The reaction has an acidic pH optimum, consistent with its occurrence in a lysosome-like compartment in vivo. Antibody blocking experiments suggest that a transient interaction between HLA-DM and the MHC class II-CLIP complex is required.

  6. Conservative compensatory Angle Class III malocclusion treatment

    Directory of Open Access Journals (Sweden)

    Marcio Costa Sobral

    2012-12-01

    Full Text Available INTRODUCTION: Angle's Class III malocclusion is a dental discrepancy in a sagittal view that may appear or not with an important skeletal discrepancy. Facial esthetics may be affected by this skeletal discrepancy and it is one of the most common complaints of patients who seek orthodontic treatment. Class III treatment, in adults, may be done by compensatory tooth movement, in simple cases, or through an association between orthodontics and orthognathic surgery, in more severe cases. OBJECTIVE: This article describes a non-extraction compensatory Class III treatment case, applying the Tweed-Merrifield mechanical principles with headgear (J-Hook in the mandibular arch. This case was presented at the V Brazilian Association of Orthodontics and Dentofacial Orthopedics (ABOR Meeting, it was evaluated by members of Brazilian Board of Orthodontics and obtained third place in the general classification.INTRODUÇÃO: a má oclusão de Classe III se caracteriza por uma desarmonia dentária anteroposterior, podendo estar ou não acompanhada por discrepâncias esqueléticas. A estética facial pode se apresentar comprometida, em maior ou menor grau, a depender da magnitude da discrepância, constituindo um dos principais fatores motivadores da procura por tratamento ortodôntico. O tratamento da Classe III em pacientes adultos pode ser realizado mediante compensação dentária, nos casos mais simples, ou, em situações mais severas, mediante a associação entre Ortodontia e Cirurgia Ortognática. OBJETIVO: o presente artigo objetiva relatar um caso clínico caracterizado por uma má oclusão de Classe III de Angle, tratado de forma compensatória, com extração dos terceiros molares inferiores, mediante a utilização de aparelhagem extrabucal na arcada inferior (J-hook, aplicando-se princípios da técnica de Tweed-Merrifield. Esse caso foi apresentado no 5º Congresso da Associação Brasileira de Ortodontia e Ortopedia Facial (ABOR, na categoria

  7. HLA class II (DR, DQ, DP) in patients with sarcoidosis: evidence of an increased frequency of DRw6

    DEFF Research Database (Denmark)

    Ødum, Niels; Milman, N; Jakobsen, B K

    1991-01-01

    The distribution of HLA class II (DR, DQ, and DP) antigens was studied in 41 patients with symptomatic sarcoidosis (SA) and ethnically matched healthy controls. HLA-DR, -DQw1 and -DQw3 typings were performed with alloantisera in the conventional microcytotoxic test, whereas -DP typings were done...

  8. [Early treatment of Class III malocclusion].

    Science.gov (United States)

    Le Gall, Michel; Philip, Camille; Salvadori, André

    2011-09-01

    Optimum treatment timing for orthodontic problems continues to be one of the more controversial topics in orthodontics. Especially regarding the correction of Class III malocclusion, there is little consensus as to proper timing or methods for correcting these problems. The orthopedic approach for growth modification is usually limited to children with growth remaining subjected to non hereditary pattern. If the skeletal malocclusion is within the range of an orthodontic treatment, fixed orthodontic appliances with dentoalveolar compensation mechanism can achieve a normal occlusion. Otherwise in patients with a severe skeletal discrepancy, it will be necessary to consider a combined surgical and orthodontic approach. The purpose of this study was to describe treatment planning according to the age and to the initial diagnosis. The management of skeletal Class III malocclusion is still a challenge to orthodontists especially because of relapse due to the late growth of the mandible. © EDP Sciences, SFODF, 2011.

  9. Contemporary solutions for managing Class III malocclusion

    Directory of Open Access Journals (Sweden)

    Nathamuni Rengarajan Krishnaswamy

    2015-01-01

    Full Text Available Although patients with Class III malocclusions constitute a small percentage of the average orthodontic practice, providing them with optimal treatment is a daunting task. The treatment approach is dependent upon the growth status of the individual and the severity of the skeletal dysplasia. For growing individuals, facemask therapy to protract the maxilla is ineffective because of its dependence on dental anchorage to bring forth skeletal correction. Orthodontic camouflage in nongrowing mild skeletal Class III individuals is met with limited success because of the anatomical boundaries and the conventional biomechanics. Orthognathic surgery to correct the maxillomandibular relations is time-consuming, and the facial esthetics is compromised during the orthodontic decompensation period. Contemporary solutions to overcome these limitations are now viable with the use of temporary anchorage devices and by performing surgery prior to orthodontic decompensation. The rationale for employing these contemporary approaches will be discussed in this study with illustrative cases.

  10. HLA-DP related suppression of mixed lymphocyte reaction with alloactivated lymphocytes

    DEFF Research Database (Denmark)

    Ødum, Niels; Hofmann, B; Jakobsen, B K

    1986-01-01

    We studied the influence of HLA class I and class II antigens on the suppression of the MLR induced by primed lymphocytes (PLs) alloactivated in vitro. The suppression of 14 different PLs of 83 MLRs was analyzed. The PLs were primed against (i) HLA-DP (SB) (ii) HLA-DR/DQ or (iii) both HLA-DP and DR...... changes in the kinetics of the MLR. Thus, HLA-DP antigens can-like DR/DQ antigens - induce PLs with the ability to suppress the MLR in an HLA-class II (DP or DR/DQ) related, and possibly a class I related, as well as an unspecific fashion....

  11. The production and crystallization of the human leukocyte antigen class II molecules HLA-DQ2 and HLA-DQ8 complexed with deamidated gliadin peptides implicated in coeliac disease

    Energy Technology Data Exchange (ETDEWEB)

    Henderson, Kate N.; Reid, Hugh H.; Borg, Natalie A.; Broughton, Sophie E.; Huyton, Trevor [The Protein Crystallography Unit, Department of Biochemistry and Molecular Biology, School of Biomedical Sciences, Monash University, Clayton, Victoria 3800 (Australia); Anderson, Robert P. [Autoimmunity and Transplantation Division, Walter and Eliza Hall Institute, 1G Royal Parade, Parkville, Victoria 3050 (Australia); Department of Gastroenterology, The Royal Melbourne Hospital, Grattan Street, Parkville, Victoria 3050 (Australia); McCluskey, James [Department of Microbiology and Immunology, University of Melbourne, Parkville, Victoria 3010 (Australia); Rossjohn, Jamie, E-mail: jamie.rossjohn@med.monash.edu.au [The Protein Crystallography Unit, Department of Biochemistry and Molecular Biology, School of Biomedical Sciences, Monash University, Clayton, Victoria 3800 (Australia)

    2007-12-01

    The production and crystallization of human leukocyte antigen class II molecules HLA-DQ2 and HLA-DQ8 in complex with deamidated gliadin peptides is reported. Crystals of HLA-DQ2{sup PQPELPYPQ} diffracted to 3.9 Å, while the HLA-DQ8{sup EGSFQPSQE} crystals diffracted to 2.1 Å, allowing structure determination by molecular replacement. The major histocompatibility complex (MHC) class II molecules HLA-DQ2 and HLA-DQ8 are key risk factors in coeliac disease, as they bind deamidated gluten peptides that are subsequently recognized by CD4{sup +} T cells. Here, the production and crystallization of both HLA-DQ2 and HLA-DQ8 in complex with the deamidated gliadin peptides DQ2 α-I (PQPELPYPQ) and DQ8 α-I (EGSFQPSQE), respectively, are reported.

  12. A human modifier of methylation for class I HLA genes (MEMO-1) maps to chromosomal bands 1p35-36.1

    NARCIS (Netherlands)

    Cheng, N. C.; Chan, A. J.; Beitsma, M. M.; Speleman, F.; Westerveld, A.; Versteeg, R.

    1996-01-01

    Class I HLA genes are expressed in almost all tissues, but expression is low or undetectable in many neuroblastomas. We analysed class I HLA methylation in normal tissues and in 28 neuroectodermal tumour cell lines. HLA-C is hypermethylated in normal adult tissues and 13 cell lines, while 15 cell

  13. Alternative Ii-independent antigen-processing pathway in leukemic blasts involves TAP-dependent peptide loading of HLA class II complexes

    NARCIS (Netherlands)

    van Luijn, M.M.; Chamuleau, M.E.D.; Ressing, M.E.; Wiertz, E.J.; Ostrand-Rosenberg, S.; Souwer, Y.; Zevenbergen, A.; Ossenkoppele, G.J.; van de Loosdrecht, A.A.; Ham, S.M.

    2010-01-01

    During HLA class II synthesis in antigen-presenting cells, the invariant chain (Ii) not only stabilizes HLA class II complexes in the endoplasmic reticulum, but also mediates their transport to specialized lysosomal antigen-loading compartments termed MIICs. This study explores an alternative HLA

  14. Broadly Immunogenic HLA Class I Supertype-Restricted Elite CTL Epitopes Recognized in a Diverse Population Infected with Different HIV-1 Subtypes

    DEFF Research Database (Denmark)

    Pérez, Carina L; Larsen, Mette Voldby; Gustafsson, Rasmus

    2008-01-01

    predicted epitopes representing seven different HLA class I supertypes that together constitute a broad coverage of the different HIV-1 strains as well as the human HLA alleles. Of the tested 184 HLA class I-restricted epitopes, 114 were recognized by at least one study subject, and 45 were novel epitopes...

  15. The mechanism of HLA-DM induced peptide exchange in the MHC class II antigen presentation pathway.

    Science.gov (United States)

    Schulze, Monika-Sarah E D; Wucherpfennig, Kai W

    2012-02-01

    HLA-DM serves a critical function in the loading and editing of peptides on MHC class II (MHCII) molecules. Recent data showed that the interaction cycle between MHCII molecules and HLA-DM is dependent on the occupancy state of the peptide binding groove. Empty MHCII molecules form stable complexes with HLA-DM, which are disrupted by binding of high-affinity peptide. Interestingly, MHCII molecules with fully engaged peptides cannot interact with HLA-DM, and prior dissociation of the peptide N-terminus from the groove is required for HLA-DM binding. There are significant similarities to the peptide loading process for MHC class I molecules, even though it is executed by a distinct set of proteins in a different cellular compartment. Copyright © 2011 Elsevier Ltd. All rights reserved.

  16. HLA class II association with autoimmune hepatitis in Latin America: a meta-analysis.

    Science.gov (United States)

    Duarte-Rey, Carolina; Pardo, Aryce L; Rodríguez-Velosa, Yolima; Mantilla, Ruben D; Anaya, Juan-Manuel; Rojas-Villarraga, Adriana

    2009-02-01

    Autoimmune hepatitis (AIH) is a chronic liver disease to which different Human Leukocyte Antigens (HLA) have been associated, according to the ethnic/geographical group affected, age of presentation, prognosis, and serologic profile. To identify common HLA class II alleles contributing to susceptibility to AIH in Latin American population. The present study was held through a systematic review of the literature, followed by a meta-analysis of 694 cases and 1769 controls of all case-control studies that supplied enough information for odd ratio and 95% confidence interval calculation conducted to date in Latin America. The serological group DQ2 was found to be risk factor for AIH, while DR5 and DQ3 were found to be protective factors in this population. At the allelic level, DQB1*02, DQB1*0603, DRB1*0405, and DRB1*1301, were found to be risk factors, while DRB1*1302 and DQB1*0301 alleles were protective factors. The physicochemical similarities and differences of critical amino acids encoding the peptide binding groove at pockets P1, P4, and P6 of these HLA molecules, elucidates their influence in the development of disease. The current study strengthens the HLA component of AIH in Latin America and its relationship to other populations around the world.

  17. 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...... associated with the following HLA class II genes were increased in PJRA when compared to normal controls: DRB1*08 (DRw8) (35.2% vs 10.3%, RR = 4.6, p less than 10(-3), DRB3*01/02/03 (DRw52) (76.3% vs 48.1%, RR 3.5, p less than 10(-3)), DQA1*0401 (41.0% vs 7.4%, RR = 7.9, p less than 10(-3)), DQA1*0501 (55...... of DNA fragments associated with the following HLA class II genes were decreased in PJRA although not statistically significantly so after 'correction' of p values: DRB1*04 (14.8% vs 40.2%, RR = 0.27; p less than 10(-3)), DRB1*07 (0% vs 25.9%, RR = 0.04, p less than 10(-3)), DRB4*0101 (DRw53) (25.9% vs...

  18. HLA class I binding of HBZ determines outcome in HTLV-1 infection.

    Science.gov (United States)

    Macnamara, Aidan; Rowan, Aileen; Hilburn, Silva; Kadolsky, Ulrich; Fujiwara, Hiroshi; Suemori, Koichiro; Yasukawa, Masaki; Taylor, Graham; Bangham, Charles R M; Asquith, Becca

    2010-09-23

    CD8(+) T cells can exert both protective and harmful effects on the virus-infected host. However, there is no systematic method to identify the attributes of a protective CD8(+) T cell response. Here, we combine theory and experiment to identify and quantify the contribution of all HLA class I alleles to host protection against infection with a given pathogen. In 432 HTLV-1-infected individuals we show that individuals with HLA class I alleles that strongly bind the HTLV-1 protein HBZ had a lower proviral load and were more likely to be asymptomatic. We also show that in general, across all HTLV-1 proteins, CD8(+) T cell effectiveness is strongly determined by protein specificity and produce a ranked list of the proteins targeted by the most effective CD8(+) T cell response through to the least effective CD8(+) T cell response. We conclude that CD8(+) T cells play an important role in the control of HTLV-1 and that CD8(+) cells specific to HBZ, not the immunodominant protein Tax, are the most effective. We suggest that HBZ plays a central role in HTLV-1 persistence. This approach is applicable to all pathogens, even where data are sparse, to identify simultaneously the HLA Class I alleles and the epitopes responsible for a protective CD8(+) T cell response.

  19. HLA class I binding of HBZ determines outcome in HTLV-1 infection.

    Directory of Open Access Journals (Sweden)

    Aidan Macnamara

    2010-09-01

    Full Text Available CD8(+ T cells can exert both protective and harmful effects on the virus-infected host. However, there is no systematic method to identify the attributes of a protective CD8(+ T cell response. Here, we combine theory and experiment to identify and quantify the contribution of all HLA class I alleles to host protection against infection with a given pathogen. In 432 HTLV-1-infected individuals we show that individuals with HLA class I alleles that strongly bind the HTLV-1 protein HBZ had a lower proviral load and were more likely to be asymptomatic. We also show that in general, across all HTLV-1 proteins, CD8(+ T cell effectiveness is strongly determined by protein specificity and produce a ranked list of the proteins targeted by the most effective CD8(+ T cell response through to the least effective CD8(+ T cell response. We conclude that CD8(+ T cells play an important role in the control of HTLV-1 and that CD8(+ cells specific to HBZ, not the immunodominant protein Tax, are the most effective. We suggest that HBZ plays a central role in HTLV-1 persistence. This approach is applicable to all pathogens, even where data are sparse, to identify simultaneously the HLA Class I alleles and the epitopes responsible for a protective CD8(+ T cell response.

  20. Class - III malocclusion: Genetics or environment? A twins study

    OpenAIRE

    Jena A; Duggal R; Mathur V; Parkash H

    2005-01-01

    Etiology of class-III malocclusion is generally believed to be genetic. A wide range of environmental factors have been suggested as contributing factors for the development of class-III malocclusion. Twin study is one of the most effective methods available for investigating genetically determined variables of malocclusion. Discordancy for class-III malocclusion is a frequent finding in dizygotic twins. However, class-III malocclusion discordancy in monozygotic twins is a rare finding. The p...

  1. HLA class II SNP interactions and the association with type 1 diabetes mellitus in Bengali speaking patients of Eastern India.

    Science.gov (United States)

    Raha, Oindrila; Sarkar, Biswanath; Lakkakula, Bhaskar V K S; Pasumarthy, Veerraju; Godi, Sudhakar; Chowdhury, Subhankar; Raychaudhuri, Pradip; Vadlamudi, Raghavendra Rao

    2013-02-27

    Several studies have demonstrated a fundamental role for the HLA in the susceptibility of, or protection to, type 1 diabetes mellitus (T1DM). However, this has not been adequately studied in Asian Indian populations. To assess the frequency of HLA class II (DPA1, DPB1, DQA1, DQB1 and DRB1) associated to susceptibility or protection toT1DM in a Bengali population of India with diabetes. Single nucleotide polymorphism study. The HLA genotyping was performed by a polymerase chain reaction followed by their HLA-DP, DQ, and DRB1 genotypes and haplotypes by sequencing method. The results are studied by Plink software. The χ2 tests were used for the inferential statistics. To our knowledge, this study is the first of a kind which has attempted to check the HLA association with T1DM by SNPs analysis. The study recruited 151 patients with T1DM and same number of ethno-linguistic, sex matched non-diabetic controls. The present study found a significant SNP rs7990 of HLA-DQA1 (p = 0.009) negative correlation, again indicating that risk from HLA is considerably more with T1DM. This study demonstrates that the HLA class-II alleles play a major role in genetic basis of T1DM.

  2. Machine learning competition in immunology – Prediction of HLA class I binding peptides

    DEFF Research Database (Denmark)

    Zhang, Guang Lan; Ansari, Hifzur Rahman; Bradley, Phil

    2011-01-01

    Experimental studies of immune system and related applications such as characterization of immune responses against pathogens, vaccine design, or optimization of therapies are combinatorially complex, time-consuming and expensive. The main methods for large-scale identification of T-cell epitopes...... of peptide binding, therefore, determines the accuracy of the overall method. Computational predictions of peptide binding to HLA, both class I and class II, use a variety of algorithms ranging from binding motifs to advanced machine learning techniques ( [Brusic et al., 2004] and [Lafuente and Reche, 2009...

  3. Sarcoidosis HLA class II genotyping distinguishes differences of clinical phenotype across ethnic groups

    Science.gov (United States)

    Sato, Hiroe; Woodhead, Felix A.; Ahmad, Tariq; Grutters, Jan C.; Spagnolo, Paolo; van den Bosch, Jules M.M.; Maier, Lisa A.; Newman, Lee S.; Nagai, Sonoko; Izumi, Takateru; Wells, Athol U.; du Bois, Roland M.; Welsh, Kenneth I.

    2010-01-01

    The HLA class II (DRB1 and DQB1) associations with sarcoidosis have been studied by several groups but often without consistent results. In this paper, we consider the hypothesis that observed inconsistencies relate to distinct, genetically encoded disease phenotypes which differ in prevalence between centres. We therefore typed HLA-DRB1 and DQB1 in 340 UK, 139 Dutch and 163 Japanese sarcoidosis patients and, respectively, 354, 218 and 168 healthy controls from these populations. We applied consistent phenotyping and genotyping and investigated associations between HLA class II alleles and distinct disease phenotypes within and between ethnic groups. DRB1*01 and DQB1*0501 are protective against all manifestations of sarcoidosis. Lung-predominant sarcoidosis is associated with DRB1*12 and *14. Löfgren's syndrome is a common sarcoidosis phenotype in the Dutch and is strongly associated with the DRB1*0301 allele. This phenotype is not seen among the Japanese in whom DRB1*0301 is absent. The same allele is protective for UK uveitis. Sarcoid uveitis is common in Japan. The DRB1*04–DQB1*0301 haplotype is a risk factor for this disease manifestation in Japanese and UK subjects but protective for sarcoidosis overall. We show that distinct sarcoidosis phenotypes have similar genetic associations across ethnic groups. The disease case mix differs between centres and may be explained by different ethnic allelic frequencies. PMID:20685690

  4. Molecular and cellular analyses of HLA class II-associated susceptibility to autoimmune diseases in the Japanese population.

    Science.gov (United States)

    Nishimura, Y; Ito, H; Fujii, S; Tabata, H; Tokano, Y; Chen, Y Z; Matsuda, I; Mitsuya, H; Kira, J; Hashimoto, H; Senju, S; Matsushita, S

    2001-06-01

    Abstract It is well known that individuals who are positive for particular HLA class II alleles show a high risk of developing autoimmune diseases. HLA class II molecules expressed on antigen-presenting cells present antigenic peptides to CD4(+) T cells. Their extensive polymorphism affects the structures of peptides bound to HLA class II molecules to create individual differences in immune responses to antigenic peptides. In order to gain a better understanding of mechanisms of the association between HLA class II alleles and susceptibility to autoimmune diseases, it is important to identify self-peptides presented by disease-susceptible HLA class II molecules and triggering disease-causative T cells. Many of the autoimmune diseases are observed in all ethnic groups, whereas the incidence of diseases, clinical manifestations and disease-susceptible HLA class II alleles are different among various ethnic groups for some autoimmune diseases. These phenomena suggest that differences in autoimmune self-peptide(s) in the context of disease-susceptible HLA class II molecules may cause these differences. Therefore, comparisons among disease-susceptible HLA class II alleles, autoantigenic peptides, and clinical manifestations of autoimmune diseases in different ethnic groups would be helpful in elucidating the pathogenesis of the diseases. In this review, we describe our recent findings on (1) the uniqueness of both clinical manifestations and the HLA-linked genetic background of Asian-type (opticospinal form) multiple sclerosis, (2) the characteristics of glutamic acid decarboxylase 65 (GAD65) or β2-glycoprotein I (β2-GPI) autoreactive T cells in Japanese patients with insulin-dependent diabetes mellitus (IDDM) or anti-β2-GPI antibody-associated autoimmunity, respectively, and (3) the generation of an efficient delivery system of peptides to the HLA class II-restricted antigen presentation path-way by utilizing a class II-associated invariant chain peptide (CLIP

  5. Lack of class I HLA expression in neuroblastoma is associated with high N-myc expression and hypomethylation due to loss of the MEMO-1 locus

    NARCIS (Netherlands)

    Cheng, N. C.; Beitsma, M.; Chan, A.; Op den Camp, I.; Westerveld, A.; Pronk, J.; Versteeg, R.

    1996-01-01

    Class I HLA expression is low in neuroblastoma tumours and cell lines. We have recently mapped a modifier of methylation for HLA-C (MEMO-1) to chromosomal bands 1p35-36.1, a region deleted in many neuroblastomas. Hypomethylation of HLA-C is strongly correlated with allelic loss of the MEMO-1 locus.

  6. HLA-G as a Tolerogenic Molecule in Transplantation and Pregnancy

    Science.gov (United States)

    da Silva Nardi, Fabiola; Wagner, Bettina; Horn, Peter A.

    2014-01-01

    HLA-G is a nonclassical HLA class I molecule. In allogeneic situations such as pregnancy or allograft transplantation, the expression of HLA-G has been related to a better acceptance of the fetus or the allograft. Thus, it seems that HLA-G is crucially involved in mechanisms shaping an allogeneic immune response into tolerance. In this contribution we focus on (i) how HLA-G is involved in transplantation and human reproduction, (ii) how HLA-G is regulated by genetic and microenvironmental factors, and (iii) how HLA-G can offer novel perspectives with respect to therapy. PMID:25143957

  7. Class III malocclusion with severe anteroposterior discrepancy

    Directory of Open Access Journals (Sweden)

    Susana Maria Deon Rizzatto

    2012-10-01

    Full Text Available This study aims at reporting the clinical case of a patient with Class III skeletal malocclusion with severe maxillary deficiency, producing a reduced midface associated with severe mandibular prognathism. The pre-surgical orthodontic preparation was composed mainly by dentoalveolar expansion and repositioning of the incisors in the lower arch. Then, a combined maxillary and mandibular orthognathic surgery was performed. The treatment objectives were achieved, with significant improvement in facial esthetics and occlusion, followed by post-treatment stability. This case was presented to the Brazilian Board of Orthodontics and Facial Orthopedics (BBO, as part of the requirements for obtaining the title of Diplomate by BBO.O objetivo deste artigo é relatar o caso clínico de um paciente portador de má oclusão de Classe III esquelética com acentuada deficiência maxilar, causando redução do terço médio da face, associada a severo prognatismo mandibular. O preparo ortodôntico pré-cirúrgico foi composto, principalmente, pela expansão dentoalveolar da maxila e o reposicionamento dos incisivos na arcada inferior. Depois, foi realizada a cirurgia ortognática combinada maxilomandibular. Os objetivos do tratamento foram atingidos, com significativa melhora da oclusão e da estética facial, seguida de estabilidade pós-tratamento. Esse caso foi apresentado à Diretoria do Board Brasileiro de Ortodontia e Ortopedia Facial (BBO, como parte dos requisitos para obtenção do título de Diplomado pelo BBO.

  8. Association of high CD4-positive T cell infiltration with mutations in HLA class II-regulatory genes in microsatellite-unstable colorectal cancer.

    Science.gov (United States)

    Surmann, Eva-Maria; Voigt, Anita Y; Michel, Sara; Bauer, Kathrin; Reuschenbach, Miriam; Ferrone, Soldano; von Knebel Doeberitz, Magnus; Kloor, Matthias

    2015-03-01

    Besides being expressed on professional antigen-presenting cells, HLA class II antigens are expressed on various tumors of non-lymphoid origin, including a subset of colorectal cancers (CRC). Information about the regulation of HLA class II antigen expression is important for a better understanding of their role in the interactions between tumor and immune cells. Whether lack of HLA class II antigen expression in tumors reflects the selective immune destruction of HLA class II antigen-expressing tumor cells is unknown. To address this question, we tested whether lack of HLA class II antigen expression in CRC was associated with immune cell infiltration. We selected microsatellite-unstable (MSI-H) CRC, because they show pronounced tumor antigen-specific immune responses and, in a subset of tumors, lack of HLA class II antigen expression due to mutations inactivating HLA class II-regulatory genes. We examined HLA class II antigen expression, mutations in regulatory genes, and CD4-positive T cell infiltration in 69 MSI-H CRC lesions. Mutations in RFX5, CIITA, and RFXAP were found in 13 (28.9%), 3 (6.7%), and 1 (2.2%) out of 45 HLA class II antigen-negative tumors. CD4-positive tumor-infiltrating lymphocyte counts were significantly higher in HLA class II antigen-negative tumors harboring mutations in HLA class II-regulatory genes (107.4 T cells per 0.25 mm(2)) compared to tumors without mutations (55.5 T cells per 0.25 mm(2), p = 0.008). Our results suggest that the outgrowth of tumor cells lacking HLA class II antigen expression due to mutations of regulatory genes is favored in an environment of dense CD4-positive T cell infiltration.

  9. Development of an assay system for large scale analysis of HLA class II-binding peptides.

    Science.gov (United States)

    Miyadera, Hiroko; Noguchi, Emiko; Mizokami, Masashi; Tokunaga, Katsushi

    2017-01-01

    Genes encoding the human leukocyte antigens (HLA) are associated with diverse immunological disorders, including autoimmune diseases and infections. Recently, significant progresses have been made in the HLA typing technologies through the use of next generation sequencers. The reliable platforms for the SNP-based imputation of HLA genotypes have also been established. These technical advancements should enable further identification of HLA associations with diseases. One of the remaining questions is the mechanism through which HLA confer disease susceptibility. As a first step toward comprehensive understanding of functional variations among HLA allele products, we established a protocol to analyze the HLA-binding peptides through quantification of cell-surface HLA expression in an engineered cell line. In this article, we summarize the overview of the cell-surface HLA expression assay, which we plan to use for screening and collection of HLA-peptide interaction profiles for large sets of HLA alleles and peptides.

  10. Condylar volume and condylar area in class I, class II and class III young adult subjects

    OpenAIRE

    Saccucci Matteo; D’Attilio Michele; Rodolfino Daria; Festa Felice; Polimeni Antonella; Tecco Simona

    2012-01-01

    Abstract Aim Aim of this study was to compare the volume and the shape of mandibular condyles in a Caucasian young adult population, with different skeletal pattern. Material and methods 200 Caucasian patients (15–30 years old, 95 male and 105 females) were classified in three groups on the base of ANB angle: skeletal class I (65 patients), skeletal class II (70 patients) and skeletal class III (65 patients). Left and right TMJs of each subject were evaluated independently with CBCT (Iluma). ...

  11. HLA Class I and II Blocks Are Associated to Susceptibility, Clinical Subtypes and Autoantibodies in Mexican Systemic Sclerosis (SSc) Patients

    Science.gov (United States)

    Rodriguez-Reyna, Tatiana S.; Mercado-Velázquez, Pamela; Yu, Neng; Alosco, Sharon; Ohashi, Marina; Lebedeva, Tatiana; Cruz-Lagunas, Alfredo; Núñez-Álvarez, Carlos; Vargas-Alarcón, Gilberto; Granados, Julio; Zúñiga, Joaquin; Yunis, Edmond

    2015-01-01

    Introduction Human leukocyte antigen (HLA) polymorphism studies in Systemic Sclerosis (SSc) have yielded variable results. These studies need to consider the genetic admixture of the studied population. Here we used our previously reported definition of genetic admixture of Mexicans using HLA class I and II DNA blocks to map genetic susceptibility to develop SSc and its complications. Methods We included 159 patients from a cohort of Mexican Mestizo SSc patients. We performed clinical evaluation, obtained SSc-associated antibodies, and determined HLA class I and class II alleles using sequence-based, high-resolution techniques to evaluate the contribution of these genes to SSc susceptibility, their correlation with the clinical and autoantibody profile and the prevalence of Amerindian, Caucasian and African alleles, blocks and haplotypes in this population. Results Our study revealed that class I block HLA-C*12:03-B*18:01 was important to map susceptibility to diffuse cutaneous (dc) SSc, HLA-C*07:01-B*08:01 block to map the susceptibility role of HLA-B*08:01 to develop SSc, and the C*07:02-B*39:05 and C*07:02-B*39:06 blocks to map the protective role of C*07:02 in SSc. We also confirmed previous associations of HLA-DRB1*11:04 and –DRB1*01 to susceptibility to develop SSc. Importantly, we mapped the protective role of DQB1*03:01 using three Amerindian blocks. We also found a significant association for the presence of anti-Topoisomerase I antibody with HLA-DQB1*04:02, present in an Amerindian block (DRB1*08:02-DQB1*04:02), and we found several alleles associated to internal organ damage. The admixture estimations revealed a lower proportion of the Amerindian genetic component among SSc patients. Conclusion This is the first report of the diversity of HLA class I and II alleles and haplotypes Mexican patients with SSc. Our findings suggest that HLA class I and class II genes contribute to the protection and susceptibility to develop SSc and its different clinical

  12. High-accuracy imputation for HLA class I and II genes based on high-resolution SNP data of population-specific references.

    Science.gov (United States)

    Khor, S-S; Yang, W; Kawashima, M; Kamitsuji, S; Zheng, X; Nishida, N; Sawai, H; Toyoda, H; Miyagawa, T; Honda, M; Kamatani, N; Tokunaga, K

    2015-12-01

    Statistical imputation of classical human leukocyte antigen (HLA) alleles is becoming an indispensable tool for fine-mappings of disease association signals from case-control genome-wide association studies. However, most currently available HLA imputation tools are based on European reference populations and are not suitable for direct application to non-European populations. Among the HLA imputation tools, The HIBAG R package is a flexible HLA imputation tool that is equipped with a wide range of population-based classifiers; moreover, HIBAG R enables individual researchers to build custom classifiers. Here, two data sets, each comprising data from healthy Japanese individuals of difference sample sizes, were used to build custom classifiers. HLA imputation accuracy in five HLA classes (HLA-A, HLA-B, HLA-DRB1, HLA-DQB1 and HLA-DPB1) increased from the 82.5-98.8% obtained with the original HIBAG references to 95.2-99.5% with our custom classifiers. A call threshold (CT) of 0.4 is recommended for our Japanese classifiers; in contrast, HIBAG references recommend a CT of 0.5. Finally, our classifiers could be used to identify the risk haplotypes for Japanese narcolepsy with cataplexy, HLA-DRB1*15:01 and HLA-DQB1*06:02, with 100% and 99.7% accuracy, respectively; therefore, these classifiers can be used to supplement the current lack of HLA genotyping data in widely available genome-wide association study data sets.

  13. Definitive class I human leukocyte antigen expression in gestational placentation: HLA-F, HLA-E, HLA-C, and HLA-G in extravillous trophoblast invasion on placentation, pregnancy, and parturition.

    Science.gov (United States)

    Hackmon, Rinat; Pinnaduwage, Lakmini; Zhang, Jianhong; Lye, Stephen J; Geraghty, Daniel E; Dunk, Caroline E

    2017-06-01

    The extravillous trophoblasts (EVT) express HLA-C and HLA-G, but HLA-E and HLA-F are the subject of conflicting reports. In this study, we define the HLA expression profile during active EVT placental implantation, pregnancy development, and parturition. Immunohistochemistry, q-PCR, and Western blot were used to investigate HLA-C, HLA-E, and HLA-F placental expression across gestation from the early first trimester, late first trimester, second trimester (n=10 in each), preterm gestation (n=6) to elective term cesarean section and term vaginal deliveries (n=12, 38-41 weeks). EVT explants and Swan71 cells were used to assess HLA-C and HLA-F during active EVT migration. HLA-G, HLA-C, and HLA-F were expressed by 1st-trimester EVT and became intracellular and weaker as gestation progressed. HLA-E was only expressed in 1st-trimester placenta. HLA-F and HLA-C mRNA and protein expression levels showed a significant increase in the fetal villous mesenchyme across gestation. HLA-C levels increased with labor. We detected a 100-kDa HLA-F band in early pregnancy suggesting dimer formation on the EVT surface. These results were confirmed in EVT outgrowths and Swan71 trophoblast which showed that HLA-F and HLA-G are increased on the cell surface of migrating EVT, while HLA-C was internalized. Expression of HLA-F and HLA-G on the cell surface of actively migrating EVT supports their specific role in early EVT invasion and interactions with uterine natural killer cells. HLA-C's limited expression to the proliferative EVT suggests a protective role in the earliest events of implantation but not in active EVT invasion. We also show for the first time that HLA-C may be involved in parturition. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  14. Set Theory Applied to the Mathematical Characterization of HLA Class II Binding Peptides

    Directory of Open Access Journals (Sweden)

    Javier Rodríguez Velásquez, MD, esp.1

    2008-04-01

    Full Text Available Antigen presentation contains the molecularbasis for antigenic identification and immuneresponses. The set theory and experimental datawere used in order to develop an union core regionmathematic characterization through the definitionof 8 laws associated to HLA class II binding.The laws were applied to 4 promiscuous peptides,25 natural peptides sequences of core region: 13binding peptides and 12 no binding peptides; and19 synthetic peptides looking to differentiate peptides.Only one peptide was not rightly characterized.This methodology may be used to choose keypeptides in the development of vaccine.

  15. Associations between sarcoidosis clinical course and ANXA11 rs1049550 C/T, BTNL2 rs2076530 G/A, and HLA class I and II alleles.

    Science.gov (United States)

    Morais, Antonio; Lima, Bruno; Alves, Helena; Melo, Natalia; Mota, Patricia C; Marques, Agostinho; Delgado, Luis

    2016-09-24

    A genetic background may be responsible for the different clinical courses in sarcoidosis. We analyzed associations between sarcoidosis clinical course and HLA class I/II alleles and susceptibility gene SNPs ANXA11 rs1049550 C/T and BTNL2 rs2076530 G/A in a Portuguese population, investigating possible gene-gene interactions. We studied 138 unrelated Caucasian sarcoidosis patients (78 women, 56.5%; mean age, 37.2 ± 12.1 years). Disease that persisted after 2 years was considered chronic. Samples were genotyped for ANXA11 rs1049550 C/T and BTNL2 rs2076530 G/A SNPs using TaqMan Real-Time PCR Assays. HLA class I/II alleles were typed using PCR sequence-specific primers. Sixty-six patients experienced disease resolution and 72 (52%) developed chronic disease. Comparison of rs1049550 and rs2076530 allele frequencies showed no significant differences. Only the HLA DRB1*03 allele was significantly associated with disease resolution (21.2% vs 4.9% for chronic disease; RR = 0.35; P < .01 after Bonferroni correction). In the logistic regression models evaluating the association between HLA alleles and chronic sarcoidosis adjusted for rs1049550 and rs2076530, only DRB1*03 was significantly associated with disease resolution. No significant interactions were found in any of the logistic regression analyses. In this population of Caucasian patients with sarcoidosis, only DRB1*03 was associated with disease resolution after 2 years' follow-up, with no significant interactions found for susceptibility gene SNPs ANXA11 rs1049550 or BTNL2 rs2076530. © 2016 John Wiley & Sons Ltd.

  16. Assembly and intracellular transport of HLA-DM and correction of the class II antigen-processing defect in T2 cells.

    Science.gov (United States)

    Denzin, L K; Robbins, N F; Carboy-Newcomb, C; Cresswell, P

    1994-10-01

    MHC class II molecules expressed in T2 cells fail to acquire a normal complement of endocytically generated peptides. The defect is repaired by introducing HLA-DMA and HLA-DMB cDNA expression vectors, determined by the restoration of SDS stability of class II alpha beta dimers, restoration of a normal conformation for HLA-DR3 as detected by a monoclonal antibody, and by a reduction in class II-associated invariant chain peptides. The intracellular distribution of class II and invariant chain molecules is also restored to that of wild-type cells. The HLA-DMA and HLA-DMB products appear to form a heterodimer that, although transported at least to the medial Golgi, is not expressed at the cell surface. These findings are consistent with HLA-DM functioning intracellularly to facilitate class II-restricted antigen processing.

  17. Trafficking of major histocompatibility complex class II molecules through intracellular compartments containing HLA-DM.

    Science.gov (United States)

    Robbins, N F; Hammond, C; Denzin, L K; Pan, M; Cresswell, P

    1996-01-01

    The endosomal site(s) where MHC class II molecules become competent to bind antigenic peptide has not been completely characterized. We identified endocytic compartments through which newly synthesized MHC class II molecules move prior to their expression on the plasma membrane. The compartments co-sediment with lysosomes in the most dense regions of Percoll gradients. The appearance of proteolytic fragments of the invariant chain (I chain), namely leupeptin-induced proteins (LIPs) and class-II-associated invariant chain peptides (CLIP), in this region of the gradient suggests that the release of MHC class II molecules from I chain association occurs within these vesicles. The formation of SDS-stable alpha beta dimers indicated that MHC class II molecules contained within these compartments are receptive to peptide binding. A majority of the HLA-DM protein was found in the same region of the Percoll gradient, consistent with its established function in MHC class-II-restricted antigen presentation. Immunoelectron micrographs of dense-sedimenting compartments indicated that I chain, MHC class II, and DM molecules are contained within both multivesicular and multilamellar vesicles. The final stages of I chain dissociation from MHC class II molecules and DM-mediated peptide loading probably occur in these compartments.

  18. Lack of association between parenchymal neurocysticercosis and HLA Class I and Class II antigens

    Directory of Open Access Journals (Sweden)

    Eni Picchioni Bompeixe

    1999-03-01

    Full Text Available Neurocysticercosis, caused by encysted larvae of the tapeworm Taenia solium, is the most common infection of the central nervous system and a major public health problem in many countries. Prevalence in the region of Curitiba, located in the southern Brazilian State of Paraná, is one of the highest in the world. The genetics of host susceptibility to neurocysticercosis (NCC is still obscure. To investigate if major histocompatibility complex (MHC genes influence individual susceptibility to NCC, we performed a case-control association analysis. Fifty-two Caucasoid patients and 149 matched controls were typed for antigens of the HLA-A, B, C, DR and DQ loci. All patients had computerized tomography and clinical features compatible with parenchymal NCC. Indirect immunofluorescence of cerebrospinal fluid showed that 19 (37% of the patients presented anti-cysticercus antibodies at titers ³ 1:10. Frequencies of HLA specificities in the whole group of patients and in the subgroup with antibodies in cerebrospinal fluid were compared to those of the control group. No significant difference was found. These results do not support the hypothesis of HLA gene participation in susceptibility to parenchymal neurocysticercosis.A neurocisticercose, causada pelo cisticerco, a larva do cestóide Taenia solium, é a infecção mais comum do sistema nervoso central e constitui importante problema de saúde pública em muitos países. A sua prevalência na região de Curitiba, localizada no Estado do Paraná, foi estimada em 9%, situando-se entre as mais elevadas do mundo. Os aspectos genéticos de suscetibilidade à neurocisticercose (NCC ainda são pouco conhecidos. Com o objetivo de investigar se genes do MHC influenciam a suscetibilidade individual à NCC, realizamos uma análise de associação caso-controle. Cinqüenta e dois pacientes caucasóides e 149 indivíduos-controle pareados foram tipados para antígenos dos locos HLA-A, B, C, DR e DQ. Todos os

  19. 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.

  20. Expansion/Facemask Treatment of an Adult Class III Malocclusion

    OpenAIRE

    Jackson, Gregory W.; Kravitz, Neal D.

    2014-01-01

    The orthodontic treatment of class III malocclusion with a maxillary deficiency is often treated with maxillary protraction with or without expansion. Skeletal and dental changes have been documented which have combined for the protraction of the maxilla and the correction of the class III malocclusion. Concerning the ideal time to treat a developing class III malocclusion, studies have reported that, although early treatment may be the most effective, face mask therapy can provide a viable o...

  1. Cranial-Base Morphology in Children with Class III Malocclusion

    OpenAIRE

    Hong-Po Chang; Tsau-Mau Chou

    2005-01-01

    The association between cranial-base morphology and Class III malocclusion is not fully understood. The purpose of this study was to investigate the morphologic characteristics of the cranial base in children with Class III malocclusion. Lateral cephalograms from 100 children with Class III malocclusion were compared with those from 100 subjects with normal occlusion. Ten landmarks on the cranial base were identified and digitized. Cephalometric assessment using seven angular and 18 linear me...

  2. ORTHODONTIC TREATMENT ALTERNATIVE TO A CLASS III SUBDIVISION MALOCCLUSION

    Science.gov (United States)

    Janson, Guilherme; de Souza, José Eduardo Prado; Barros, Sérgio Estelita Cavalcante; Andrade, Pedro; Nakamura, Alexandre Yudi

    2009-01-01

    Class III malocclusions are considered one of the most complex and difficult orthodontic problems to diagnose and treat. Skeletal and/or dental asymmetries in patients presenting with Class III malocclusions can worsen the prognosis. Recognizing the dentoalveolar and skeletal characteristics of subdivision malocclusions and their treatment possibilities is essential for a favorable nonsurgical correction. Therefore, this article presents a nonsurgical asymmetric extraction approach to Class III subdivision malocclusion treatment which can significantly improve the occlusal and facial discrepancies. PMID:19668997

  3. Human immune responsiveness to Lolium perenne pollen allergen Lol p III (rye III) is associated with HLA-DR3 and DR5.

    Science.gov (United States)

    Ansari, A A; Freidhoff, L R; Meyers, D A; Bias, W B; Marsh, D G

    1989-05-01

    A well-characterized allergen of Lolium perenne (perennial rye grass) pollen, Lol p III, has been used as a model antigen to study the genetic control of the human immune response. Associations between HLA type and IgE or IgG antibody (Ab) responsiveness to Lol p III were studied in two groups of skin-test-positive Caucasoid adults (N = 135 and 67). We found by nonparametric and parametric analyses that immune responsiveness to Lol p III was significantly associated with HLA-DR3 and DR5. No association was found between any DQ type and immune responsiveness to Lol p III. Geometric mean IgE or IgG Ab levels to Lol p III were not different between B8+, DR3+ subjects and B8-, DR3+ subjects, showing that HLA-B8 had no influence on the association. Lol p III IgG Ab data obtained on subjects after grass antigen immunotherapy showed that 100% of DR3 subjects and 100% of DR5 subjects were Ab+. A comparison of all the available protein sequences of DRB gene products showed that the first hypervariable region of DR3 and DR5 (and DRw6), and no other region, contains the sequence Glu9-Tyr-Ser-Thr-Ser13. Our observations are consistent with the possibility that immune responsiveness to the allergen Lol p III is associated with this amino acid sequence in the first hypervariable region of the DR beta 1 polypeptide chain.

  4. Class - III malocclusion: Genetics or environment? A twins study

    Directory of Open Access Journals (Sweden)

    Jena A

    2005-03-01

    Full Text Available Etiology of class-III malocclusion is generally believed to be genetic. A wide range of environmental factors have been suggested as contributing factors for the development of class-III malocclusion. Twin study is one of the most effective methods available for investigating genetically determined variables of malocclusion. Discordancy for class-III malocclusion is a frequent finding in dizygotic twins. However, class-III malocclusion discordancy in monozygotic twins is a rare finding. The purpose of this study of monozygotic twins is to assess the genetic and environmental components of variation within the cranio-dento-facial complex.

  5. The role of KIR genes and their cognate HLA class I ligands in childhood acute lymphoblastic leukemia.

    Science.gov (United States)

    de Smith, Adam J; Walsh, Kyle M; Ladner, Martha B; Zhang, Siming; Xiao, Carmen; Cohen, Franziska; Moore, Theodore B; Chokkalingam, Anand P; Metayer, Catherine; Buffler, Patricia A; Trachtenberg, Elizabeth A; Wiemels, Joseph L

    2014-04-17

    Killer cell immunoglobulin-like receptors (KIRs), via interaction with their cognate HLA class I ligands, play a crucial role in the development and activity of natural killer cells. Following recent reports of KIR gene associations in childhood acute lymphoblastic leukemia (ALL), we present a more in-depth investigation of KIR genes and their cognate HLA ligands on childhood ALL risk. Genotyping of 16 KIR genes, along with HLA class I groups C1/C2 and Bw4 supertype ligands, was carried out in 212 childhood ALL cases and 231 healthy controls. Frequencies of KIR genes, KIR haplotypes, and combinations of KIR-HLA ligands were tested for disease association using logistic regression analyses. KIR A/A genotype frequency was significantly increased in cases (33.5%) compared with controls (24.2%) (odds ratio [OR] = 1.57; 95% confidence interval [CI], 1.04-2.39). Stratifying analysis by ethnicity, a significant difference in KIR genotype frequency was demonstrated in Hispanic cases (34.2%) compared with controls (21.9%) (OR = 1.86; 95% CI, 1.05-3.31). Homozygosity for the HLA-Bw4 allele was strongly associated with increased ALL risk exclusively in non-Hispanic white children (OR = 3.93; 95% CI, 1.44-12.64). Our findings suggest a role for KIR genes and their HLA ligands in childhood ALL etiology that may vary among ethnic groups.

  6. Influence of HLA class I haplotypes on HIV-1 seroconversion and disease progression in Pumwani sex worker cohort.

    Science.gov (United States)

    Sampathkumar, Raghavan; Peters, Harold O; Mendoza, Lillian; Bielawny, Thomas; Ngugi, Elizabeth; Kimani, Joshua; Wachihi, Charles; Plummer, Francis A; Luo, Ma

    2014-01-01

    We examined the effect of HLA class I haplotypes on HIV-1 seroconversion and disease progression in the Pumwani sex worker cohort. This study included 595 HIV-1 positive patients and 176 HIV negative individuals. HLA-A, -B, and -C were typed to 4-digit resolution using sequence-based typing method. HLA class I haplotype frequencies were estimated using PyPop 32-0.6.0. The influence of haplotypes on time to seroconversion and CD4+ T cell decline to single allele within the haplotypes. The true haplotype effect was observed with A*30∶02-B*45∶01, A*30∶02-C*16∶02, B*53∶01-C*04∶01 B*15∶10-C*03∶04, and B*42∶01-C*17∶01. In these cases, the presence of both alleles accelerated the disease progression or seroconversion than any of the single allele within the haplotypes. Our study showed that the true effects of HLA class I haplotypes on HIV seroconversion and disease progression exist and the associations of HLA class I haplotype can also be due to the dominant effect of a single allele within the haplotype.

  7. HLA Class I Binding 9mer Peptides from Influenza A Virus Induce CD4(+) T Cell Responses

    DEFF Research Database (Denmark)

    Wang, M. J.; Larsen, Mette Voldby; Nielsen, Morten

    2010-01-01

    Background: Identification of human leukocyte antigen class I (HLA-I) restricted cytotoxic T cell (CTL) epitopes from influenza virus is of importance for the development of new effective peptide-based vaccines. Methodology/Principal Findings: In the present work, bioinformatics was used to predict...... 9mer peptides derived from available influenza A viral proteins with binding affinity for at least one of the 12 HLA-I supertypes. The predicted peptides were then selected in a way that ensured maximal coverage of the available influenza A strains. One hundred and thirty one peptides were...... synthesized and their binding affinities for the HLA-I supertypes were measured in a biochemical assay. Influenza-specific T cell responses towards the peptides were quantified using IFN gamma ELISPOT assays with peripheral blood mononuclear cells (PBMC) from adult healthy HLA-I typed donors as responder...

  8. Class III Malocclusion Surgical-Orthodontic Treatment

    Directory of Open Access Journals (Sweden)

    Bruna Alves Furquim

    2014-01-01

    Full Text Available The aim of the present case report is to describe the orthodontic-surgical treatment of a 17-year-and-9-month-old female patient with a Class III malocclusion, poor facial esthetics, and mandibular and chin protrusion. She had significant anteroposterior and transverse discrepancies, a concave profile, and strained lip closure. Intraorally, she had a negative overjet of 5 mm and an overbite of 5 mm. The treatment objectives were to correct the malocclusion, and facial esthetic and also return the correct function. The surgical procedures included a Le Fort I osteotomy for expansion, advancement, impaction, and rotation of the maxilla to correct the occlusal plane inclination. There was 2 mm of impaction of the anterior portion of the maxilla and 5 mm of extrusion in the posterior region. A bilateral sagittal split osteotomy was performed in order to allow counterclockwise rotation of the mandible and anterior projection of the chin, accompanying the maxillary occlusal plane. Rigid internal fixation was used without any intermaxillary fixation. It was concluded that these procedures were very effective in producing a pleasing facial esthetic result, showing stability 7 years posttreatment.

  9. CD4+ T-cell alloreactivity toward mismatched HLA class II alleles early after double umbilical cord blood transplantation.

    Science.gov (United States)

    Lamers, Cor H J; Wijers, Rebecca; van Bergen, Cornelis A M; Somers, Judith A E; Braakman, Eric; Gratama, Jan Willem; Debets, Reno; Falkenburg, J H Frederik; Cornelissen, Jan J

    2016-10-27

    Although double umbilical cord blood transplantation (dUCBT) in adult patients may be associated with less graft failure compared with single UCBT, hematopoietic recovery generally originates from a single cord blood unit (CBU). CBU predominance is still incompletely understood. We recently showed that blood CD4 + T-cell numbers rapidly increase after dUCBT, and early CD4 + T-cell chimerism predicts for graft predominance. Given the frequent HLA class II allele mismatches between CBUs in dUCBT, we hypothesized that alloreactive HLA class II-specific CD4 + T cells from the "winning" CBU may contribute to rejection of the "loser" CBU. We evaluated whether CD4 + T cells originating from the predominant (PD)-CBU would recognize HLA class II allele mismatches, expressed by the nonengrafting (NE)-CBU. Alloreactive effector CD4 + T cells toward 1 or more mismatched HLA class II alleles of the NE-CBU were detected in 11 of 11 patients, with reactivity toward 29 of 33 (88%) tested mismatches, and the strongest reactivity toward DR and DQ alleles early after dUCBT. Mismatched HLA class II allele-specific CD4 + T cells recognized primary leukemic cells when the mismatched HLA class II allele was shared between NE-CBU and patient. Our results suggest that cytotoxicity exerted by CD4 + T cells from the PD-CBU drives the rapid rejection of the NE-CBU, whose alloreactive effect might also contribute to graft-versus-leukemia. © 2016 by The American Society of Hematology.

  10. Association between HLA Class I Alleles and Proviral Load in HTLV-I Associated Myelopathy/Tropical Spastic Paraperesis (HAM/TSP) Patients in Iranian Population.

    Science.gov (United States)

    Taghaddosi, Mahdi; Rezaee, S A Rahim; Rafatpanah, Houshang; Rajaei, Taraneh; Farid Hosseini, Reza; Narges, Valizadeh

    2013-03-01

    The aim of this study was to investigate the association between HLA class I alleles (HLA-A*02, HLA-A*24, HLA-Cw*08, HLA-B5401) and proviral load in HTLV-I associated myelopathy/tropical spastic paraperesis (HAM/TSP) patients in Iranian population. 20 new cases of HAM/TSP patients and 30 HTLV-I infected healthy carriers were recruited. Peripheral blood samples were collected. Peripheral blood mononuclear cells (PBMCs) were isolated. DNA was extracted from PBMC.HTLV-I proviral load was calculated by Taqman quantitative real time polymerase chain reaction (qRT-PCR). PCR sequence-specific primer (PCR-SSP) reactions were performed to detect HLA-A, HLA-B and, HLA-Cw alleles. There was no significant difference in sex and age between asymptomatic and HAM/TSP group. The Mann-Whitney U test was used to compare proviral load between HAM/TSP patients and healthy carrier. Provirus load of HAM/TSP patients was significantly higher than that of HCs (P=0.003, Mann-Whitney U test).Odd ratio was calculated to determine association between class I alleles including (HLA-A*02, HLA-A*24, HLA-Cw*08) and risk of HAM/TSP development. We couldn't find any association between these class I alleles and risk of HAM/TSP development in our study. In our survey HLA-A*02, HLA-A24, HLA-Cw*08 didn't have protective effect on proviral load (P=0.075, P=0.060 and 0.650 Mann-Whitney U test respectively). In conclusion, certain HLA alleles with protective effect in one population may have not similar effect in other population. This may be because of pathogen polymorphism or host genetic heterogeneity and allele frequency in desired population.

  11. HLA profile in patients with AIDS and tuberculosis

    Directory of Open Access Journals (Sweden)

    José Fernando de Castro Figueiredo

    Full Text Available Studies carried out in various populations have reported an association between some HLA specificities and susceptibility to tuberculosis. We investigated the class I and class II HLA profile in Brazilian patients of various ethnic backgrounds who had AIDS and tuberculosis. Twenty-two adult patients with AIDS and tuberculosis (Group I, 103 patients with AIDS without tuberculosis (Group II and 423 healthy individuals not infected with HIV (Group III were evaluated. Diagnosis of HIV infection was made by ELISA, confirmed by a gelatin particle agglutination test. Diagnosis of tuberculosis was made based on clinical/radiological presentation and direct bacilloscopy or clinical specimen cultures. Class I antigens were typed by microlymphotoxicity. Class II alleles were characterized by the polymerase chain reaction (PCR. Differences in frequency of HLA specificities between groups were found in the following antigens/alleles: Group I x Group II: HLA-A31 - p=0.026; HLA-B41 - p= 0.037; HLA-DRB1*10 - p=0.037; HLA-DQB1*5 - p=0.009. Group I x Group III (control: HLA-A31 - p = 0.000008; odds ratio (OR=31.75; HLA-B41 - p=0.003; HLA-DQB1*5 - p=0.02. HLA-A31 and HLA-B41 antigens and the HLA-DRB1*10 and HLA-DQB1*05 alleles were over-represented in patients with AIDS and tuberculosis (Group I, suggesting that these HLA molecules are associated with susceptibility to tuberculosis in Brazilian patients with AIDS.

  12. HLA class II alleles in Norwegian patients with coexisting type 1 diabetes and celiac disease.

    Science.gov (United States)

    Viken, M K; Flåm, S T; Skrivarhaug, T; Amundsen, S S; Sollid, L M; Drivvoll, A K; Joner, G; Dahl-Jørgensen, K; Lie, B A

    2017-05-01

    Type 1 diabetes (T1D) and celiac disease (CeD) are 2 distinct diseases, but there is an increased risk of developing CeD for T1D patients. Both diseases are associated with HLA-class II alleles, such as DQB1 *02:01 and DQB1 *03:02; however, their risk contribution vary between the diseases. We genotyped HLA-DRB1 and - DQB1 in 215 patients with coexisting T1D and CeD identified from a T1D cohort, and compared them to patients with T1D (N = 487) and CeD (N = 327), as well as healthy controls (N = 368). The patients with coexisting T1D and CeD had an intermediate carrier frequency (72.8%) of the DRB1 *03:01- DQB1 *02:01- DQA1 *05:01 haplotype compared to T1D (64.1%) and CeD (88.7%) patients. The DRB1 *03:01- DQB1 *02:01- DQA1 *05:01/ DRB1 *04- DQB1 *03:02- DQA1 *03 haplotype combination, encoding DQ2.5 and DQ8 molecules, was equally frequent among patients with both T1D and CeD (52.6%) and T1D patients (46.8%) but significantly lower in CeD patients (9.5%). Overall, the patients with coexisting T1D and CeD had an HLA profile more similar to T1D patients than CeD patients. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  13. Evidence of differential HLA class I-mediated viral evolution in functional and accessory/regulatory genes of HIV-1.

    Directory of Open Access Journals (Sweden)

    Zabrina L Brumme

    2007-07-01

    Full Text Available Despite the formidable mutational capacity and sequence diversity of HIV-1, evidence suggests that viral evolution in response to specific selective pressures follows generally predictable mutational pathways. Population-based analyses of clinically derived HIV sequences may be used to identify immune escape mutations in viral genes; however, prior attempts to identify such mutations have been complicated by the inability to discriminate active immune selection from virus founder effects. Furthermore, the association between mutations arising under in vivo immune selection and disease progression for highly variable pathogens such as HIV-1 remains incompletely understood. We applied a viral lineage-corrected analytical method to investigate HLA class I-associated sequence imprinting in HIV protease, reverse transcriptase (RT, Vpr, and Nef in a large cohort of chronically infected, antiretrovirally naïve individuals. A total of 478 unique HLA-associated polymorphisms were observed and organized into a series of "escape maps," which identify known and putative cytotoxic T lymphocyte (CTL epitopes under selection pressure in vivo. Our data indicate that pathways to immune escape are predictable based on host HLA class I profile, and that epitope anchor residues are not the preferred sites of CTL escape. Results reveal differential contributions of immune imprinting to viral gene diversity, with Nef exhibiting far greater evidence for HLA class I-mediated selection compared to other genes. Moreover, these data reveal a significant, dose-dependent inverse correlation between HLA-associated polymorphisms and HIV disease stage as estimated by CD4(+ T cell count. Identification of specific sites and patterns of HLA-associated polymorphisms across HIV protease, RT, Vpr, and Nef illuminates regions of the genes encoding these products under active immune selection pressure in vivo. The high density of HLA-associated polymorphisms in Nef compared to other

  14. Condylar volume and condylar area in class I, class II and class III young adult subjects.

    Science.gov (United States)

    Saccucci, Matteo; D'Attilio, Michele; Rodolfino, Daria; Festa, Felice; Polimeni, Antonella; Tecco, Simona

    2012-12-14

    Aim of this study was to compare the volume and the shape of mandibular condyles in a Caucasian young adult population, with different skeletal pattern. 200 Caucasian patients (15-30 years old, 95 male and 105 females) were classified in three groups on the base of ANB angle: skeletal class I (65 patients), skeletal class II (70 patients) and skeletal class III (65 patients). Left and right TMJs of each subject were evaluated independently with CBCT (Iluma). TMJ evaluation included: condylar volume; condylar area; morphological index (MI). Condylar volumes were calculated by using the Mimics software. The condylar volume, the area and the morphological index (MI) were compared among the three groups, by using non-parametric tests. The Kruskal-Wallis test and the Mann Whitney test revealed that: no significant difference was observed in the whole sample between the right and the left condylar volume; subjects in skeletal class III showed a significantly higher condylar volume, respect to class I and class II subjects (p condylar volume was observed in class II subjects, respect to class I and class III (p condylar volume (699.8 ± 63.07 mm3 in males and 663.5 ± 81.3 mm3 in females; p condylar surface (423.24 ± 63.03 mm2 in males and 389.76 ± 61.15 mm2 in females; p condylar volume and to the mandibular condylar area in the Caucasian orthodontic population.

  15. Interdisciplinary orthognathic treatment of high angle class III ...

    African Journals Online (AJOL)

    For Class III adult patients, combined treatment strategy must be followed which includes either further dentoalveolar compensation or orthognathic surgery following decompensation of the teeth. This case report presents the interdisciplinary approach of a skeletal Class III malocclusion with increased vertical facial ...

  16. The Clinical effectiveness of sequential treatment of skeletal class III ...

    African Journals Online (AJOL)

    Aim: To assess the dentofacial changes induced by the sequential treatment in the skeletal class III malocclusion with maxillary retrognathism. Study design: Controlled clinical trial assessing the effectiveness of sequential treatment of skeletal class III malocclusion. Materials and Methods: The treated group consisted of 30 ...

  17. The shape and size of the sella turcica in skeletal Class I, Class II, and Class III Saudi subjects

    National Research Council Canada - National Science Library

    Alkofide, Eman A

    2007-01-01

    ...; 60 Class I, 60 Class II, and 60 Class III. The sella turcica on each radiograph was analysed and measured to determine the shape of the sella, in addition to the linear dimensions of length, depth, and diameter...

  18. Condylar volume and condylar area in class I, class II and class III young adult subjects

    Directory of Open Access Journals (Sweden)

    Saccucci Matteo

    2012-12-01

    Full Text Available Abstract Aim Aim of this study was to compare the volume and the shape of mandibular condyles in a Caucasian young adult population, with different skeletal pattern. Material and methods 200 Caucasian patients (15–30 years old, 95 male and 105 females were classified in three groups on the base of ANB angle: skeletal class I (65 patients, skeletal class II (70 patients and skeletal class III (65 patients. Left and right TMJs of each subject were evaluated independently with CBCT (Iluma. TMJ evaluation included: condylar volume; condylar area; morphological index (MI. Condylar volumes were calculated by using the Mimics software. The condylar volume, the area and the morphological index (MI were compared among the three groups, by using non-parametric tests. Results The Kruskal-Wallis test and the Mann Whitney test revealed that: no significant difference was observed in the whole sample between the right and the left condylar volume; subjects in skeletal class III showed a significantly higher condylar volume, respect to class I and class II subjects (p 3 in males and 663.5 ± 81.3 mm3 in females; p 2 in males and 389.76 ± 61.15 mm2 in females; p  Conclusion Skeletal class appeared to be associated to the mandibular condylar volume and to the mandibular condylar area in the Caucasian orthodontic population.

  19. Expansion/Facemask Treatment of an Adult Class III Malocclusion

    Directory of Open Access Journals (Sweden)

    Gregory W. Jackson

    2014-01-01

    Full Text Available The orthodontic treatment of class III malocclusion with a maxillary deficiency is often treated with maxillary protraction with or without expansion. Skeletal and dental changes have been documented which have combined for the protraction of the maxilla and the correction of the class III malocclusion. Concerning the ideal time to treat a developing class III malocclusion, studies have reported that, although early treatment may be the most effective, face mask therapy can provide a viable option for older children as well. But what about young adults? Can the skeletal and dental changes seen in expansion/facemask therapy in children and adolescents be demonstrated in this age group as well, possibly eliminating the need for orthodontic dental camouflage treatment or orthognathic surgery? A case report is presented of an adult class III malocclusion with a Class III skeletal pattern and maxillary retrusion. Treatment was with nonextraction, comprehensive edgewise mechanics with slow maxillary expansion with a bonded expander and protraction facemask.

  20. Cranial-base morphology in children with class III malocclusion.

    Science.gov (United States)

    Chang, Hong-Po; Hsieh, Shu-Hui; Tseng, Yu-Chuan; Chou, Tsau-Mau

    2005-04-01

    The association between cranial-base morphology and Class III malocclusion is not fully understood. The purpose of this study was to investigate the morphologic characteristics of the cranial base in children with Class III malocclusion. Lateral cephalograms from 100 children with Class III malocclusion were compared with those from 100 subjects with normal occlusion. Ten landmarks on the cranial base were identified and digitized. Cephalometric assessment using seven angular and 18 linear measurements was performed by univariate and multivariate analyses. The results revealed that the greatest between-group differences occurred in the posterior cranial-base region. It was concluded that shortening and angular bending of the cranial base, and a diminished angle between the cranial base and mandibular ramus, may lead to Class III malocclusion associated with Class III facial morphology. The association between cranial-base morphology and other types of malocclusion needs clarification. Further study of regional changes in the cranial base, with geometric morphometric analysis, is warranted.

  1. Expansion/Facemask Treatment of an Adult Class III Malocclusion.

    Science.gov (United States)

    Jackson, Gregory W; Kravitz, Neal D

    2014-01-01

    The orthodontic treatment of class III malocclusion with a maxillary deficiency is often treated with maxillary protraction with or without expansion. Skeletal and dental changes have been documented which have combined for the protraction of the maxilla and the correction of the class III malocclusion. Concerning the ideal time to treat a developing class III malocclusion, studies have reported that, although early treatment may be the most effective, face mask therapy can provide a viable option for older children as well. But what about young adults? Can the skeletal and dental changes seen in expansion/facemask therapy in children and adolescents be demonstrated in this age group as well, possibly eliminating the need for orthodontic dental camouflage treatment or orthognathic surgery? A case report is presented of an adult class III malocclusion with a Class III skeletal pattern and maxillary retrusion. Treatment was with nonextraction, comprehensive edgewise mechanics with slow maxillary expansion with a bonded expander and protraction facemask.

  2. Occlusal rehabilitation of pseudo-class III patient.

    Science.gov (United States)

    Cardoso, Antônio Carlos; Ferreira, Cimara Fortes; Oderich, Elisa; Pedroso, Moira Leão; Wicks, Russell

    2015-01-01

    To treat a patient with anterior crossbite, the clinician should first assess if it is a genuine class III or a pseudo-class III malocclusion. Cephalometric analysis is important; however, registering a patient's centric relation (CR) is simple, quick, and costless and can play a decisive role in a differential diagnosis for this type of patient profile. This clinical report depicts a patient clinically diagnosed as class III. After mandible manipulation in CR, it was noted that the patient in question was a pseudo-class III. The treatment was based on the pseudo-class III diagnosis. Therefore, the patient was rehabilitated by occlusal adjustments and conventional and implant-supported prostheses and without the need for invasive orthognathic surgery. © 2014 by the American College of Prosthodontists.

  3. Considerations before orthodontic camouflage treatment in skeletal class III malocclusion

    Directory of Open Access Journals (Sweden)

    Marcella Budhiawan

    2008-03-01

    Full Text Available Skeletal Class III malocclusions are caused by maxillary deficiency, mandibular protrusion, or a combination of the two. This patient, in this case, may have a sunken in face, strong chin appearance. Most persons with Class III malocclusions, which is a dentofacial deformity, show combinations of skeletal and dentoalveolar components. Orthodontic therapy is usually aimed at compensating for the underlying mild-moderate skeletal Class III discrepancy and patients with severe skeletal Class III discrepancies require a combination of orthodontic treatment and orthognathic surgery to correct the underlying skeletal pattern. By considering many factors, the orthodontic treatment can be done on mild to severe skeletal Class III. These factors are facial profile, dental relationship and skeletal pattern. Those factors should be considered a starting point in making a treatment decision. They give the limitation of orthodontic treatment in terms of whether the occlusion could be corrected, or whether the deformity could be camouflage.

  4. Targeted identification of infection-related HLA class I-presented epitopes by stable isotope tagging of epitopes (SITE).

    Science.gov (United States)

    Meiring, H D; Soethout, E C; de Jong, A P J M; van Els, C A C M

    2007-05-01

    Identification of peptides presented in human leukocyte antigen (HLA) class I molecules after viral infection is of strategic importance for immunology and vaccine development. A powerful strategy aimed at the rapid, unambiguous identification of naturally processed HLA class I-associated peptides, which are induced by viral infection, is presented here. The methodology, stable isotope tagging of epitopes (SITE), is based on metabolic labeling of endogenously synthesized proteins during infection. This is accomplished by culturing virus-infected cells with stable isotope-labeled amino acids that are expected to be anchor residues for the human leukocyte antigen allele of interest. Subsequently, these cells are mixed with an equal number of noninfected cells, which are cultured in normal medium. Finally, peptides are acid-eluted from immunoprecipitated HLA molecules and subjected to two-dimensional nanoscale liquid chromatography-mass spectrometry analysis. Virus-induced peptides are identified through computer-assisted detection of characteristic, binomially distributed ratios of labeled and unlabeled molecules.

  5. The MHC class II cofactor, HLA-DM, interacts with immunoglobulin in B cells

    Science.gov (United States)

    Ayyangar, Sashi; Jiang, Wei; Rajasekaran, Narendiran; Spura, Armin; Hessell, Ann J.; Madec, Anne-Marie; Mellins, Elizabeth D.

    2014-01-01

    B cells internalize extracellular antigen into endosomes using the immunoglobulin (Ig) component of the B cell receptor. In endosomes, antigen-derived peptides are loaded onto MHC class II proteins (MHC-II). How these pathways intersect remains unclear. We find that HLA-DM (DM), a catalyst for MHC-II peptide loading, co-precipitates with Ig in lysates from human tonsillar B cells and B cell lines. The molecules in the Ig/DM complexes have mature glycans, and the complexes co-localize with endosomal markers in intact cells. A larger fraction of Ig precipitates with DM after BCR crosslinking, implying that complexes can form when DM meets endocytosed Ig. In vitro, in the endosomal pH range, soluble HLA-DM (sDM) directly binds the Ig Fab domain, and increases levels of free antigen released from immune complexes. Together, these results argue that DM and Ig intersect in the endocytic pathway of B cells with potential functional consequences. PMID:25098292

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

    Science.gov (United States)

    Cruz-Tapias, Paola; Pérez-Fernández, Oscar M; Rojas-Villarraga, Adriana; Rodríguez-Rodríguez, Alberto; Arango, María-Teresa; Anaya, Juan-Manuel

    2012-01-01

    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.

  7. Susceptibility to amoxicillin-clavulanate-induced liver injury is influenced by multiple HLA class I and II alleles.

    Science.gov (United States)

    Lucena, M Isabel; Molokhia, Mariam; Shen, Yufeng; Urban, Thomas J; Aithal, Guruprasad P; Andrade, Raúl J; Day, Christopher P; Ruiz-Cabello, Francisco; Donaldson, Peter T; Stephens, Camilla; Pirmohamed, Munir; Romero-Gomez, Manuel; Navarro, Jose Maria; Fontana, Robert J; Miller, Michael; Groome, Max; Bondon-Guitton, Emmanuelle; Conforti, Anita; Stricker, Bruno H C; Carvajal, Alfonso; Ibanez, Luisa; Yue, Qun-Ying; Eichelbaum, Michel; Floratos, Aris; Pe'er, Itsik; Daly, Mark J; Goldstein, David B; Dillon, John F; Nelson, Matthew R; Watkins, Paul B; Daly, Ann K

    2011-07-01

    Drug-induced liver injury (DILI), especially from antimicrobial agents, is an important cause of serious liver disease. Amoxicillin-clavulanate (AC) is a leading cause of idiosyncratic DILI, but little is understood about genetic susceptibility to this adverse reaction. We performed a genome-wide association study using 822,927 single nucleotide polymorphism (SNP) markers from 201 White European and US cases of DILI following AC administration (AC-DILI) and 532 population controls, matched for genetic background. AC-DILI was associated with many loci in the major histocompatibility complex. The strongest effect was with an HLA class II SNP (rs9274407, P=4.8×10(-14)), which correlated with rs3135388, a tag SNP of HLA-DRB1*1501-DQB1*0602 that was previously associated with AC-DILI. Conditioned on rs3135388, rs9274407 is still significant (P=1.1×10(-4)). An independent association was observed in the class I region (rs2523822, P=1.8×10(-10)), related to HLA-A*0201. The most significant class I and II SNPs showed statistical interaction (P=.0015). High-resolution HLA genotyping (177 cases and 219 controls) confirmed associations of HLA-A*0201 (P=2×10(-6)) and HLA-DQB1*0602 (P=5×10(-10)) and their interaction (P=.005). Additional, population-dependent effects were observed in HLA alleles with nominal significance. In an analysis of autoimmune-related genes, rs2476601 in the gene PTPN22 was associated (P=1.3×10(-4)). Class I and II HLA genotypes affect susceptibility to AC-DILI, indicating the importance of the adaptive immune response in pathogenesis. The HLA genotypes identified will be useful in studies of the pathogenesis of AC-DILI but have limited utility as predictive or diagnostic biomarkers because of the low positive predictive values. Copyright © 2011 AGA Institute. Published by Elsevier Inc. All rights reserved.

  8. The Relationship of HLA Class I and II Alleles and Haplotypes with Autism: A Case Control Study

    Directory of Open Access Journals (Sweden)

    Manan Al-Hakbany

    2014-01-01

    Full Text Available Earlier reports showed the relationship between autism and immune genes located in the human leukocyte antigen (HLA. In this current study, we compared the HLA class I and class II alleles and haplotypes in 35 autistic children with 100 control subjects from Saudi Arabia, using PCR-SSP method and Luminex technology. In class I the HLA-A*01 (P=0.03, OR 2.68, A*02 (P=0.001, OR 3.02 and HLA-B*07 (P=0.01, OR 3.27, were significantly associated with autism. Also, the haplotype A*02-B*07 was significantly higher in autistic patients than in controls (P=0.007, OR 5.83. In class II, DRB1*1104 was significantly higher in patients than in controls (P=0.001, OR 8.75. The DQB1*0202 (P=0.001, OR 0.24, DQB1*0302 (P=0.001, OR 0.14, and DQB1*0501 (P=0.012, OR 0.25, were negatively associated with disease. While the four-loci genotype study showed that A*01-B*07-DRB1*0701-DQB1*0602 (P=0.001, OR 41.9 and the A*31-B*51-DRB1*0103-DQB1*0302 (P=0.012, OR 4.8 are positively associated with autism among Saudi patients. This is the first report on a foreseeable risk of association of HLA-B*07 allele with autism. Thus, HLA-B*07 allele and the closely linked haplotype A*01 B*07 DRB1*0701 DQB1*0602 may serve as a marker for genetic susceptibility to autism in Saudis.

  9. Recognition of nonclassical HLA class I antigens by gamma delta T cells during pregnancy.

    Science.gov (United States)

    Barakonyi, Aliz; Kovacs, Katalin T; Miko, Eva; Szereday, Laszlo; Varga, Peter; Szekeres-Bartho, Julia

    2002-03-15

    The healthy trophoblast does not express classical HLA-A and HLA-B products; therefore, an MHC-restricted recognition of trophoblast-presented Ags is unlikely. In the decidua and also in peripheral blood of healthy pregnant women, gammadelta T cells significantly increase in number. We investigated the possible role of gammadelta T cells in recognition of trophoblast-presented Ags. PBL and isolated gammadelta T cells from healthy pregnant women as well as from those at risk for premature pregnancy termination were conjugated to choriocarcinoma cells (JAR) transfected with nonclassical HLA Ags (HLA-E, HLA-G). To investigate the involvement of killer-inhibitory/killer-activatory receptors in trophoblast recognition, we tested the effect of CD94 block on cytotoxic activity of Vdelta2(+) enriched gammadelta T cells to HLA-E- and/or HLA-G-transfected targets. Lymphocytes from healthy pregnant women preferentially recognized HLA(-) choriocarcinoma cells, whereas those from pathologically pregnant patients did not discriminate between HLA(+) and HLA(-) cells. Normal pregnancy Vdelta2(+) T cells conjugated at a significantly increased rate to HLA-E transfectants, whereas Vdelta2(+) lymphocytes from pathologically pregnant women did not show a difference between those and HLA(-) cells. Blocking of the CD94 molecule of Vdelta2(+) lymphocytes from healthy pregnant women resulted in an increased cytotoxic activity to HLA-E-transfected target cells. These data indicate that Vdelta2(+) lymphocytes of healthy pregnant women recognize HLA-E on the trophoblast, whereas Vdelta1 cells react with other than HLA Ags. In contrast to Vdelta2(+) lymphocytes from healthy pregnant women, those from women with pathological pregnancies do not recognize HLA-E via their killer-inhibitory receptors and this might account for their high cytotoxic activity.

  10. Presence of third molar germs in orthodontic patients with class II/2 and class III malocclusions.

    Science.gov (United States)

    Mady Maricić, Barbara; Legović, Mario; Slaj, Martina; Lapter Varga, Marina; Zuvić Butorac, Marta; Kapović, Miljenko

    2009-12-01

    The aim of this study was to determine the presence of third molar germs in patients with Class II/2 and Class III malocclusions. The study comprised 146 examinees from Zagreb and Istria. Examinees with Class II/2 malocclusions amounted to 77 and those with Class III 69. With regard to development of dentition the examinees were divided into two groups: Group I subjects with early mixed dentition (23 subjects with Class II/2 and 21 subjects with Class III), and Group II subjects with late mixed dentition (54 subjects with Class II/2 and 48 subjects with Class III). Assessments were made from panoramic radiographs and lateral cephalograms. The Pearson chi2-test and Fisher's exact test was used to determine statistical significance in differences. Assessments showed that third molar germs were present significantly more often in the upper jaw in Class II/2 (58% vs. 44%) and in the lower jaw in Class III (83% vs. 69%). In subjects with Class II/2 all third molar germs were present statistically more often in late mixed dentition, which was also determined for maxillary third molar germs in Class III. The presence of mandibular third molar germs in Class III examinees was almost equal in both periods of mixed dentitions. The study confirmed correlation between the presence of third molar germs and sagital maxillomandibular relationship and encourages investigation of the differences in calcifications of all permanent teeth in such malocclusions.

  11. HLA II class alleles in juvenile idiopathic arthritis patients with and without temporomandibular joint arthritis.

    Science.gov (United States)

    Dāvidsone, Zane; Eglīte, Jeļena; Lazareva, Arina; Dzelzīte, Sarmīte; Šantere, Ruta; Bērziņa, Dace; Staņēviča, Valda

    2016-04-19

    Temporomandibular joint (TMJ) arthritis is seen very often (38-87 %) in children with juvenile idiopathic arthritis (JIA). With contrast enhanced magnetic resonance imaging (MRI) we can detect more cases of TMJ arthritis than ever before. Previous studies show that HLA II class alleles may have protective or risk importance in JIA subtypes. Our objective is to identify HLA II class alleles of risk and protection in JIA patients with TMJ arthritis. During the period from 2010 to 2015 MRI for TMJ was performed in 85 JIA patients who were genotyped for HLA- DRB1; DQB1 and DQA1 using RT-PCR with sequence-specific primers. As a control group, data of 100 individuals were taken from the genetic bank of RSU Joint Laboratory of Clinical Immunology and Immunogenetics. Associations of DRB1; DQB1; DQA1 alleles in patients were examined individually using the χ (2) test. P-value (disease was 3.07 ± 2.35 years (range 0.2-11.0 year). JIA subtypes were as follows: seronegative polyarthritis 51 (60 %), seropositive polyarthritis 6(7 %), oligoarthritis extended 7(8 %), oligoarthritis persistent 2 (2 %) arthritis with enthesitis 14 (17 %), undifferentiated 3 (4 %) and 2 (2 %) systemic arthritis. Two groups where separated after TMJ MRI exam: first with at least two signs of active inflammation and/or any structural damage (n = 62); second with no pathologic signs or with slight contrast enhancement (n = 23). We discovered that there are risk alleles that are found in all JIA patient's groups (MRI positive and negative groups) versus controls such as DRB1*07:01, DQB1*03:03; DQB1*05:01. Also some protective alleles as DRB1*18:01, DQB1*06:02-8 were found in overall JIA group. Alleles DRB1*12:01, DQB1*03:01; DQA1*05:01 were found to be protective for TMJ arthrits. In our study there were no convincing risk alleles, but there are alleles that probably are protective for TMJ arthritis like DRB1*12:01, DQB1*03:01; DQA1*05:01.

  12. Type 1 Diabetes in the Spanish Population: additional factors to Class II HLA-DR3 and -DR4

    Directory of Open Access Journals (Sweden)

    Ibarra José M

    2005-04-01

    Full Text Available Abstract Background The Major Histocompatibility Complex is the main genetic contributor to susceptibility to type 1 diabetes (T1D; genome-wide scans have consistently mapped increased predisposition to this region. The highest disease risk has been associated with HLA-DR3 and HLA-DR4. In particular, the DR3-positive ancestral haplotype 18.2 was reported as highly diabetogenic. We aimed to corroborate whether this haplotype increases the susceptibility conferred by the DQ2-DR3 alleles in a Mediterranean population. We also searched for additional susceptibility factors to the classic DQ2-DR3 and DQ8-DR4. Results Genetic MHC markers were analysed in a case-control study with 302 T1D patients and 529 ethnically matched controls. DR3-TNFa1b5 carrier rate was significantly higher in DR3-positive heterozygous T1D patients than in DR3-positive heterozygous controls (p = 0.0019; odds ratio OR [95% confidence interval CI] = 2.26 [1.3–3.93]. This data was confirmed analysing the allelic frequency, which includes the information corresponding to the DR3-homozygous individuals (p = 0.001; OR = 2.09 and by using the Arlequin software to check the DR3-positive haplotypes (p = 0.004;OR = 1.93. The present results provide strong evidence of a second susceptibility region in the ancestral haplotype 18.2 in the Spanish population. Moreover, we searched for T1D susceptibility factors in addition to the MHC classical ones, within the DR2-DQ6/DR3-DQ2/DR4-DQ8 negative population. Several genetic markers in both MHC class II (DQA1*0101-DQB1*0501 [p = 0.007;OR = 2.81], DQA1*0201-DQB1*0202 [p = 0.03; OR = 2.35] and III (TNFa2b1 [p = 0.01 OR = 2.74], BAT-2*2 [p = 0.004; OR = 3.19] were found. These different alleles associated with T1D were not independent and we observed linkage disequilibrium among them leading us to describe two new risk haplotypes (DQA1*0101-DQB1*0501-TNFa2b1 and DQA1*0201-DQB1*0202- BAT-2*2. Finally, we studied a T1D susceptibility

  13. Genome-wide association study identifies new HLA class II haplotypes strongly protective against narcolepsy

    DEFF Research Database (Denmark)

    Hor, Hyun; Kutalik, Zoltán; Dauvilliers, Yves

    2010-01-01

    Narcolepsy is a rare sleep disorder with the strongest human leukocyte antigen (HLA) association ever reported. Since the associated HLA-DRB1*1501-DQB1*0602 haplotype is common in the general population (15-25%), it has been suggested that it is almost necessary but not sufficient for developing......*0602. We found association with a protective variant near HLA-DQA2 (rs2858884; P ... ratio = 0.02; P HLA haplotype suggests a virtually causal involvement of the HLA region in narcolepsy susceptibility....

  14. HLA-DO increases bacterial superantigen binding to human MHC molecules by inhibiting dissociation of class II-associated invariant chain peptides.

    Science.gov (United States)

    Pezeshki, Abdul Mohammad; Azar, Georges A; Mourad, Walid; Routy, Jean-Pierre; Boulassel, Mohamed-Rachid; Denzin, Lisa K; Thibodeau, Jacques

    2013-10-01

    HLA-DO (H2-O in mice) is an intracellular non-classical MHC class II molecule (MHCII). It forms a stable complex with HLA-DM (H2-M in mice) and shapes the MHC class II-associated peptide repertoire. Here, we tested the impact of HLA-DO and H2-O on the binding of superantigens (SAgs), which has been shown previously to be sensitive to the structural nature of the class II-bound peptides. We found that the binding of staphylococcal enterotoxin (SE) A and B, as well as toxic shock syndrome toxin 1 (TSST-1), was similar on the HLA-DO(+) human B cell lines 721.45 and its HLA-DO(-) counterpart. However, overexpressing HLA-DO in MHC class II(+) HeLa cells (HeLa-CIITA-DO) improved binding of SEA and TSST-1. Accordingly, knocking down HLA-DO expression using specific siRNAs decreased SEA and TSST-1 binding. We tested directly the impact of the class II-associated invariant chain peptide (CLIP), which dissociation from MHC class II molecules is inhibited by overexpressed HLA-DO. Loading of synthetic CLIP on HLA-DR(+) cells increased SEA and TSST-1 binding. Accordingly, knocking down HLA-DM had a similar effect. In mice, H2-O deficiency had no impact on SAgs binding to isolated splenocytes. Altogether, our results demonstrate that the sensitivity of SAgs to the MHCII-associated peptide has physiological basis and that the effect of HLA-DO on SEA and TSST-1 is mediated through the inhibition of CLIP release. Copyright © 2013 American Society for Histocompatibility and Immunogenetics. Published by Elsevier Inc. All rights reserved.

  15. 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

    We investigated the DNA restriction fragment length polymorphism (RFLP) of the Major Histocompatability Complex (MHC) class II genes: HLA-DRB, -DQA, -DQB, DPA, and -DFB in 24 patients with rheumatoid arthritis (RA), in 19 patients with primary Sjögren's syndrome (primary SS), and healthy Danes....... 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.......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...

  16. HLA-D gene studies in relation to immune responsiveness to a grass allergen Lol p III.

    Science.gov (United States)

    Ansari, A A; Shinomiya, N; Zwollo, P; Marsh, D G

    1991-01-01

    The grass pollen allergen Lol p III (Mr 11,000) is a well-characterized antigen that has been found useful in immunogenetic studies of human immune responsiveness. Since immune responsiveness to this allergen is associated with HLA-DR3, we investigated whether there was any sequence in the HLA-D region that would render a person "susceptible" [antibody (Ab)-positive] to the allergen. By sequence-specific oligonucleotide (SSO) slot-blot and sequence analyses of polymerase chain reaction (PCR)-amplified genomic DNA from Lol p III responder and nonresponder subjects, Ab responsiveness was found to be strongly associated with the sequence Glu-Tyr-Ser-Thr-Ser (EYSTS), present in the first polymorphic regions of DR beta I polypeptide chains of DR3, DR11 (split of DR5), and DRw6. Of the 41 grass-allergic subjects investigated, 19 had the EYSTS sequence, of whom 18 (95%) were Lol p III immunoglobulin G (IgG) Ab responders; among the 22 EYSTS- subjects, ten were Lol p III responders (P = 0.001, relative risk = 21.6). No such association was found with any polymorphic sequences in other DR beta chains, or in DQ alpha I and DQ beta I chains. These findings suggest that the EYSTS sequence is important in the presentation of an epitope of Lol p III; other sequence(s) may be involved in the presentation of other epitope(s). To our knowledge, this is the first demonstration of a strong association between a specific HLA sequence and immune responsiveness to a well-defined antigen. The paper shows that presence of the EYSTS sequence classifies subjects as Lol p III responders in 18/19 cases.

  17. Exclusion of Class III malocclusion candidate loci in Brazilian families.

    Science.gov (United States)

    Cruz, R M; Hartsfield, J K; Falcão-Alencar, G; Koller, D L; Pereira, R W; Mah, J; Ferrari, I; Oliveira, S F

    2011-10-01

    The role played by genetic components in the etiology of the Class III phenotype, a class of dental malocclusion, is not yet understood. Regions that may be related to the development of Class III malocclusion have been suggested previously. The aim of this study was to search for genetic linkage with 6 microsatellite markers (D1S234, D4S3038, D6S1689, D7S503, D10S1483, and D19S566), near previously proposed candidate regions for Class III. We performed a two-point parametric linkage analysis for 42 affected individuals from 10 Brazilian families with a positive Class III malocclusion segregation. Analysis of our data indicated that there was no evidence for linkage of any of the 6 microsatellite markers to a Class III locus at = zero, with data supporting exclusion for 5 of the 6 markers evaluated. The present work reinforces that Class III is likely to demonstrate locus heterogeneity, and there is a dependency of the genetic background of the population in linkage studies.

  18. An HLA class-II allele frequent in Eskimos and Amerindians is found in the Tyrolean Ice Man.

    Science.gov (United States)

    Fischer, G F; Fae, I; Mann, D; Kriks, D; Jäger, W; Platzer, W; Mayr, W R; Volc-Platzer, B

    2001-07-01

    DNA was extracted from specimens derived from the calcaneus of the Tyrolean Ice Man under sterile conditions in a laboratory, where no DNA extractions and PCR experiments had been performed before. Agarose gel electrophoresis and ethidium bromide staining did not reveal any evidence of genomic DNA in the preparation obtained, indicating a high degree of DNA degradation. Nevertheless, we performed PCR amplifications with this sample using primer pairs specific for HLA class II alleles. HLA-DRB and DQB1 alleles were amplified in a nested PCR approach. In one of the reactions, we observed a distinct amplification product, which we directly sequenced. By comparing the obtained nucleotide sequence with a database of HLA alleles we assigned the HLA-DRB1*1402 type to the amplified sample. None of the investigators involved possesses this allele, indicating that no contamination with modern DNA had occurred. The HLA-DRB1*1402 allele is extremely rare in Europe, but is common in Inuits and South American Indians and has previously only once been identified in the laboratory.

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

    Directory of Open Access Journals (Sweden)

    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.

  20. Non-surgical treatment of skeletal class III malocclusion.

    Science.gov (United States)

    Kapadia, Romina M; Shah, Adit P; Diyora, Shamil D; Rathva, Vandana J

    2014-04-10

    The incidence of skeletal class III malocclusion has a mean of 3% in the Caucasian population, 5% in African-American adolescents and about 14% in the Asian population. In India, the incidence of class III malocclusion is reported to be 3.4%. A patient having class III malocclusion shows findings ranging from edge-to-edge bite to large reverse overjet, with extreme variations of underlying skeletal jaw bases and craniofacial form. This is a case report of a 20-year-old man having skeletal class III malocclusion with concave profile, anterior crossbite and a negative overjet of 3 mm treated non-surgically with extraction of only one lower left first premolar.

  1. Components of adult class III malocclusion in an Iranian population

    Directory of Open Access Journals (Sweden)

    Roodabeh Koodaryan

    2009-03-01

    Full Text Available Background and aims. Class III malocclusions are considered complex and difficult orthodontic problems to diagnose and treat. The purpose of this study was to investigate the morphologic characteristics of the craniofacial complex of adults with Class III malocclusion in an Iranian population. Materials and methods. Lateral cephalometric radiographs of 50 patients with Class III malocclusion (20 males and 30 females; age range of 18-27 years were selected on the basis of molar relationship, concave profile and an overjet of ≤ 0 mm. The standard values of 19 soft tissue measurements were determined using McNamara, Burstone and Viazis methods. Results. Adults with Class III malocclusion exhibited distinct craniofacial morphologic characteristics manifested by a combination of retrusion of maxilla and protrusion of mandible. Conclusion. The most prevalent component was mandibular prognathism, normal maxilla and LAFH on the basis of the component analysis.

  2. Two classes of region III flagellar genes in Escherichia coli.

    OpenAIRE

    Kondoh, H; Ozeki, H.

    1981-01-01

    We infected various nonflagellated mutants of Escherichia coli with fla-transducing phages and followed the kinetics of the appearance of motility. Our analysis revealed two distinct classes of region III fla genes. Class II fla genes (hag, flaD) functioned 15 min later than class I fla genes (flaN, flaB, flaC, flaO, flaA, flbD, flaQ, flaP) in flagellar morphogenesis. We suggest that the two classes of fla genes are involved in two different stages, initiation (class I) and completion (class ...

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

    Directory of Open Access Journals (Sweden)

    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.

  4. Diagnosis and Treatment of Pseudo-Class III Malocclusion

    OpenAIRE

    Ariel Reyes; Luis Serret; Marcos Peguero; Orlando Tanaka

    2014-01-01

    Pseudo-Class III malocclusion is characterized by the presence of an anterior crossbite due to a forward functional displacement of the mandible; in most cases, the maxillary incisors present some degree of retroclination, and the mandibular incisors are proclined. Various types of appliances have been described in the literature for the early treatment of pseudo-Class III malocclusion. The objectives of this paper are to demonstrate the importance of making the differential diagnosis between...

  5. Conservative treatment of Angle Class III malocclusion with anterior crossbite.

    Science.gov (United States)

    de Aguiar, João Hélder Ferreira

    2015-01-01

    Angle Class III malocclusion is characterized by anteroposterior dental discrepancy which might be associated or not with skeletal changes. Class III molar relationship is associated with vertical or lingually tipped mandibular incisors and a usually concave profile. These characteristics seriously affect facial esthetics and most frequently are the reason why patients seek orthodontic treatment. This case was presented to the committee of the Brazilian Board of Orthodontics and Facial Orthopedics (BBO) as part of the requisites to become a BBO Diplomate.

  6. Identification of amino acids in antigen-binding site of class II HLA proteins independently associated with hepatitis B vaccine response.

    Science.gov (United States)

    Sakai, Aiko; Noguchi, Emiko; Fukushima, Takashi; Tagawa, Manabu; Iwabuchi, Atsushi; Kita, Masaki; Kakisaka, Keisuke; Miyasaka, Akio; Takikawa, Yasuhiro; Sumazaki, Ryo

    2017-01-23

    Genetic factors in class II human leukocyte antigen (HLA) have been reported to be associated with inter-individual variation in hepatitis B virus (HBV) vaccine response. However, the mechanism underlying the associations remains elusive. In particular, the broad linkage disequilibrium in HLA region complicates the localization of the independent effects of genetic variants. Thus, the present study aimed to identify the most probable causal variations in class II HLA loci involved in the immune response to HBV vaccine. We performed a case-control study to assess whether HLA-DRB1, -DQB1, and -DPB1 4-digit alleles were associated with the response to primary HBV vaccination in 574 healthy Japanese students. To identify causative variants, we next assessed independently associated amino acid variants in these loci using conditional logistic regression analysis. Furthermore, to clarify the functional effects of these variants on HLA proteins, we performed computational structural studies. HLA-DRB1∗01:01, HLA-DRB1∗08:03, HLA-DQB1∗05:01, and HLA-DPB1∗04:02 were significantly associated with sufficient response, whereas HLA-DPB1∗05:01 was associated with poor response. We then identified amino acids independently associated with sufficient response, namely, leucine at position 26 of HLA-DRβ1 and glycine-glycine-proline-methionine at positions 84-87 of HLA-DPβ1. These amino acids were located in antigen-binding pocket 4 of HLA-DR and pocket 1 of HLA-DP, respectively, which are important structures for selective binding of antigenic peptides. In addition, the detected variations in HLA-DP protein were responsible for the differences in the electrostatic potentials of the pocket, which can explain in part the sufficient/poor vaccine responses. HLA-DRβ1 position 26 and HLA-DPβ1 positions 84-87 are independently associated with anti-HBs production against HBV vaccine. Our results suggest that HBsAg presentation through these HLA pocket structures plays an

  7. A benefit-risk assessment of class III antiarrhythmic agents

    DEFF Research Database (Denmark)

    Elming, Hanne; Brendorp, Bente; Pehrson, Steen

    2004-01-01

    relief. Since many patients experience a decrease in physical performance as well as a diminished quality of life during arrhythmia there is still a need for antiarrhythmic drug therapy. The development of new antiarrhythmic agents has changed the focus from class I to class III agents since it became...... evident that with class I drug therapy the prevalence of mortality is considerably higher. This review focuses on the benefits and risks of known and newer class III antiarrhythmic agents. The benefits discussed include the ability to maintain sinus rhythm in persistent atrial fibrillation patients......, and reducing the need for implantable cardioverter defibrillator shock/antitachycardia therapy, since no class III antiarrhythmic agents have proven survival benefit. The risks discussed mainly focus on pro-arrhythmia as torsade de pointes ventricular tachycardia....

  8. Disparate associations of HLA class I markers with HIV-1 acquisition and control of viremia in an African population.

    Directory of Open Access Journals (Sweden)

    Wei Song

    Full Text Available Acquisition of human immunodeficiency virus type 1 (HIV-1 infection is mediated by a combination of characteristics of the infectious and the susceptible member of a transmission pair, including human behavioral and genetic factors, as well as viral fitness and tropism. Here we report on the impact of established and potential new HLA class I determinants of heterosexual HIV-1 acquisition in the HIV-1-exposed seronegative (HESN partners of serodiscordant Zambian couples.We assessed the relationships of behavioral and clinically documented risk factors, index partner viral load, and host genetic markers to HIV-1 transmission among 568 cohabiting couples followed for at least nine months. We genotyped subjects for three classical HLA class I genes known to influence immune control of HIV-1 infection. From 1995 to December 2006, 240 HESNs seroconverted and 328 remained seronegative. In Cox proportional hazards models, HLA-A*68:02 and the B*42-C*17 haplotype in HESN partners were significantly and independently associated with faster HIV-1 acquisition (relative hazards = 1.57 and 1.55; p = 0.007 and 0.013, respectively after controlling for other previously established contributing factors in the index partner (viral load and specific class I alleles, in the HESN partner (age, gender, or in the couple (behavioral and clinical risk score. Few if any previously implicated class I markers were associated here with the rate of acquiring infection.A few HLA class I markers showed modest effects on acquisition of HIV-1 subtype C infection in HESN partners of discordant Zambian couples. However, the striking disparity between those few markers and the more numerous, different markers found to determine HIV-1 disease course makes it highly unlikely that, whatever the influence of class I variation on the rate of infection, the mechanism mediating that phenomenon is identical to that involved in disease control.

  9. Disparate Associations of HLA Class I Markers with HIV-1 Acquisition and Control of Viremia in an African Population

    Science.gov (United States)

    Song, Wei; He, Dongning; Brill, Ilene; Malhotra, Rakhi; Mulenga, Joseph; Allen, Susan; Hunter, Eric; Tang, Jianming; Kaslow, Richard A.

    2011-01-01

    Background Acquisition of human immunodeficiency virus type 1 (HIV-1) infection is mediated by a combination of characteristics of the infectious and the susceptible member of a transmission pair, including human behavioral and genetic factors, as well as viral fitness and tropism. Here we report on the impact of established and potential new HLA class I determinants of heterosexual HIV-1 acquisition in the HIV-1-exposed seronegative (HESN) partners of serodiscordant Zambian couples. Methodology/Principal Findings We assessed the relationships of behavioral and clinically documented risk factors, index partner viral load, and host genetic markers to HIV-1 transmission among 568 cohabiting couples followed for at least nine months. We genotyped subjects for three classical HLA class I genes known to influence immune control of HIV-1 infection. From 1995 to December 2006, 240 HESNs seroconverted and 328 remained seronegative. In Cox proportional hazards models, HLA-A*68:02 and the B*42-C*17 haplotype in HESN partners were significantly and independently associated with faster HIV-1 acquisition (relative hazards = 1.57 and 1.55; p = 0.007 and 0.013, respectively) after controlling for other previously established contributing factors in the index partner (viral load and specific class I alleles), in the HESN partner (age, gender), or in the couple (behavioral and clinical risk score). Few if any previously implicated class I markers were associated here with the rate of acquiring infection. Conclusions/Significance A few HLA class I markers showed modest effects on acquisition of HIV-1 subtype C infection in HESN partners of discordant Zambian couples. However, the striking disparity between those few markers and the more numerous, different markers found to determine HIV-1 disease course makes it highly unlikely that, whatever the influence of class I variation on the rate of infection, the mechanism mediating that phenomenon is identical to that involved in

  10. The impact of HLA class I and EBV latency-II antigen-specific CD8(+) T cells on the pathogenesis of EBV(+) Hodgkin lymphoma.

    Science.gov (United States)

    Jones, K; Wockner, L; Brennan, R M; Keane, C; Chattopadhyay, P K; Roederer, M; Price, D A; Cole, D K; Hassan, B; Beck, K; Gottlieb, D; Ritchie, D S; Seymour, J F; Vari, F; Crooks, P; Burrows, S R; Gandhi, M K

    2016-02-01

    In 40% of cases of classical Hodgkin lymphoma (cHL), Epstein-Barr virus (EBV) latency-II antigens [EBV nuclear antigen 1 (EBNA1)/latent membrane protein (LMP)1/LMP2A] are present (EBV(+) cHL) in the malignant cells and antigen presentation is intact. Previous studies have shown consistently that HLA-A*02 is protective in EBV(+) cHL, yet its role in disease pathogenesis is unknown. To explore the basis for this observation, gene expression was assessed in 33 cHL nodes. Interestingly, CD8 and LMP2A expression were correlated strongly and, for a given LMP2A level, CD8 was elevated markedly in HLA-A*02(-) versus HLA-A*02(+) EBV(+) cHL patients, suggesting that LMP2A-specific CD8(+) T cell anti-tumoral immunity may be relatively ineffective in HLA-A*02(-) EBV(+) cHL. To ascertain the impact of HLA class I on EBV latency antigen-specific immunodominance, we used a stepwise functional T cell approach. In newly diagnosed EBV(+) cHL, the magnitude of ex-vivo LMP1/2A-specific CD8(+) T cell responses was elevated in HLA-A*02(+) patients. Furthermore, in a controlled in-vitro assay, LMP2A-specific CD8(+) T cells from healthy HLA-A*02 heterozygotes expanded to a greater extent with HLA-A*02-restricted compared to non-HLA-A*02-restricted cell lines. In an extensive analysis of HLA class I-restricted immunity, immunodominant EBNA3A/3B/3C-specific CD8(+) T cell responses were stimulated by numerous HLA class I molecules, whereas the subdominant LMP1/2A-specific responses were confined largely to HLA-A*02. Our results demonstrate that HLA-A*02 mediates a modest, but none the less stronger, EBV-specific CD8(+) T cell response than non-HLA-A*02 alleles, an effect confined to EBV latency-II antigens. Thus, the protective effect of HLA-A*02 against EBV(+) cHL is not a surrogate association, but reflects the impact of HLA class I on EBV latency-II antigen-specific CD8(+) T cell hierarchies. © 2015 The Authors. Clinical & Experimental Immunology published by John Wiley & Sons Ltd on

  11. Analysis of the CD8+T cell anti-HIV activity in heterologous cell co-cultures reveals the benefit of multiple HLA class I matches.

    Science.gov (United States)

    Killian, M Scott; Teque, Fernando; Sudhagoni, Ramu

    2018-02-01

    CD8 + T lymphocytes can reduce the production of human immunodeficiency virus 1 (HIV-1) by CD4 + T cells by cytotoxic and non-cytotoxic mechanisms. To investigate the involvement of human leukocyte antigen (HLA) class I compatibility in anti-HIV responses, we co-cultured primary CD8 + T cells, isolated from the peripheral blood of HIV-1-infected individuals, with panels of autologous and heterologous acutely HIV-1-infected primary CD4 + T cells. Altogether, CD8 + T cell anti-HIV activity was evaluated in more than 200 co-cultures. Marked heterogeneity in HIV-1 replication levels was observed among the co-cultures sharing a common CD8 + T cell source. The co-cultures that exhibited greater than 50% reduction in HIV production were found to have significantly increased numbers of matching HLA class I alleles (Yates chi-square = 54.21; p T cells from HIV controllers and asymptomatic viremic individuals, matching HLA-B and/or HLA-C alleles were more predictive of strong anti-HIV activity than matching HLA-A alleles. Overall, HLA class I genotype matches were more closely associated with CD8 + T cell anti-HIV activity than supertype pairings. Antibodies against HLA class I and CD3 reduced the CD8 + T cell anti-HIV activity. Stimulated CD8 + T cells exhibited increased anti-HIV activity and reduced dependency on HLA compatibility. These findings provide evidence that the maximal suppression of HIV replication by CD8 + T cells requires the recognition of multiple epitopes. These studies provide insight for HIV vaccine development, and the analytic approach can be useful for the functional characterization of HLA class I alleles and tentative HLA class I supertypes.

  12. Polymorphic SVA retrotransposons at four loci and their association with classical HLA class I alleles in Japanese, Caucasians and African Americans.

    Science.gov (United States)

    Kulski, Jerzy K; Shigenari, Atsuko; Inoko, Hidetoshi

    2010-04-01

    Polymorphic insertion frequencies of the retrotransposons known as the "SVA" elements were investigated at four loci in the MHC class I genomic region to determine their allele and haplotype frequencies and associations with the HLA-A, -B or -C genes for 100 Japanese, 100 African Americans, 174 Australian Caucasians and 66 reference cell lines obtained from different ethnic groups. The SVA insertions representing different subfamily members varied in frequency between none for SVA-HF in Japanese and 65% for SVA-HB in Caucasians or African Americans with significant differences in frequencies between the three populations at least at three loci. The SVA loci were in Hardy-Weinberg equilibrium except for the SVA-HA locus which deviated significantly in African Americans and Caucasians possibly because of a genomic deletion of this locus in individuals with the HLA-A*24 allele. Strong linkage disequilibria and high percentage associations between the human leucocyte antigen (HLA) class I gene alleles and some of the SVA insertions were detected in all three populations in spite of significant frequency differences for the SVA and HLA class I alleles between the three populations. The highest percentage associations (>86%) were between SVA-HB and HLA-B*08, -B*27, -B*37 to -B*41, -B*52 and -B*53; SVA-HC and HLA-B*07; SVA-HA and HLA-A*03, -A*11 and -A*30; and SVA-HF and HLA-A*03 and HLA-B*47. From pairwise associations in the three populations and the homozygous cell line results, it was possible to deduce the SVA and HLA class I allelic combinations (haplotypes), population differences and the identity by descent of several common HLA-A allelic lineages.

  13. 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)

    Creary, L. E.; Brunet, L.; Galan, M.; Pasquier, M.; Kervaire, B.; Langaney, A.; Tiercy, J.‐M.; Fernández‐Viña, M. A.; Nunes, J. M.

    2017-01-01

    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. PMID:29160618

  14. Postura de cabeça nas deformidades dentofaciais classe II e classe III Head posture in the presence of class II and class III dentofacial deformities

    Directory of Open Access Journals (Sweden)

    Marcela Ralin de Carvalho Deda

    2012-04-01

    Full Text Available OBJETIVO: este estudo investiga se existe diferença entre grupos com diferentes deformidades dentofaciais (padrão classe II e classe III e o grupo sem a deformidade em relação à postura de cabeça. MÉTODO: participaram deste estudo, voluntariamente, 25 pacientes (entre 16 e 40 anos. Dez pacientes com diagnóstico de deformidade dentofacial classe II e 15 pacientes com o diagnóstico de classe III esquelética e 15 voluntários sadios, com equivalência em sexo e idade ao grupo de deformidade, formando o grupo controle. Primeiramente foi realizada a inspeção da postura de cabeça. Logo em seguida foi realizada a avaliação postural de cabeça por meio da fotografia postural (fotogrametria. RESULTADOS: não houve diferença significante (p>0,05 entre os grupos em relação à avaliação postural utilizando-se a fotogrametria. Já em relação à avaliação postural pela inspeção clínica, observou-se uma postura anterior de cabeça nos indivíduos com a deformidade dentofacial padrão classe II, comparados ao padrão classe III (p = 0,001 e ao grupo controle (p = 0,001. Foi visto também que o grupo deformidade classe II apresentou um percentual inferior de indivíduos com posição neutra de cabeça comparado ao grupo deformidade classe III (p = 0,008 e ao grupo controle (p = 0,001. CONCLUSÃO: indivíduos com deformidade dentofacial classe II podem apresentar uma anteriorização de cabeça. Não há influência da deformidade no aumento ou na redução do ângulo cabeça-pescoço, analisado por meio da fotogrametria.PURPOSE: this study investigates whether there is a difference in head posture between groups with different dentofacial deformities (class II and class III and a group with no deformity. METHOD: 25 volunteers aged from 16 to 40 year old took part in the study. Ten patients had a diagnosis of class II dentofacial deformity, 15 had a diagnosis of class III skeletal deformity, and 15 healthy volunteers matched for sex and

  15. Ability of HIV-1 Nef to downregulate CD4 and HLA class I differs among viral subtypes.

    Science.gov (United States)

    Mann, Jaclyn K; Byakwaga, Helen; Kuang, Xiaomei T; Le, Anh Q; Brumme, Chanson J; Mwimanzi, Philip; Omarjee, Saleha; Martin, Eric; Lee, Guinevere Q; Baraki, Bemuluyigza; Danroth, Ryan; McCloskey, Rosemary; Muzoora, Conrad; Bangsberg, David R; Hunt, Peter W; Goulder, Philip J R; Walker, Bruce D; Harrigan, P Richard; Martin, Jeff N; Ndung'u, Thumbi; Brockman, Mark A; Brumme, Zabrina L

    2013-09-16

    The highly genetically diverse HIV-1 group M subtypes may differ in their biological properties. Nef is an important mediator of viral pathogenicity; however, to date, a comprehensive inter-subtype comparison of Nef in vitro function has not been undertaken. Here, we investigate two of Nef's most well-characterized activities, CD4 and HLA class I downregulation, for clones obtained from 360 chronic patients infected with HIV-1 subtypes A, B, C or D. Single HIV-1 plasma RNA Nef clones were obtained from N=360 antiretroviral-naïve, chronically infected patients from Africa and North America: 96 (subtype A), 93 (B), 85 (C), and 86 (D). Nef clones were expressed by transfection in an immortalized CD4+ T-cell line. CD4 and HLA class I surface levels were assessed by flow cytometry. Nef expression was verified by Western blot. Subset analyses and multivariable linear regression were used to adjust for differences in age, sex and clinical parameters between cohorts. Consensus HIV-1 subtype B and C Nef sequences were synthesized and functionally assessed. Exploratory sequence analyses were performed to identify potential genotypic correlates of Nef function. Subtype B Nef clones displayed marginally greater CD4 downregulation activity (p = 0.03) and markedly greater HLA class I downregulation activity (p class I downregulation remained statistically significant after controlling for differences in age, sex, and clinical parameters (p A/D > C for Nef-mediated CD4 and HLA class I downregulation. The mechanisms underlying these differences and their relevance to HIV-1 pathogenicity merit further investigation.

  16. 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.

  17. MHC Class I Chain-Related Gene A Polymorphisms and Linkage Disequilibrium with HLA-B and HLA-C Alleles in Ocular Toxoplasmosis

    Science.gov (United States)

    Ayo, Christiane Maria; Camargo, Ana Vitória da Silveira; Frederico, Fábio Batista; Siqueira, Rubens Camargo; Previato, Mariana; Murata, Fernando Henrique Antunes; Silveira-Carvalho, Aparecida Perpétuo; Barbosa, Amanda Pires; Brandão de Mattos, Cinara de Cássia; de Mattos, Luiz Carlos

    2015-01-01

    This study investigated whether polymorphisms of the MICA (major histocompatibility complex class I chain-related gene A) gene are associated with eye lesions due to Toxoplasma gondii infection in a group of immunocompetent patients from southeastern Brazil. The study enrolled 297 patients with serological diagnosis of toxoplasmosis. Participants were classified into two distinct groups after conducting fundoscopic exams according to the presence (n = 148) or absence (n = 149) of ocular scars/lesions due to toxoplasmosis. The group of patients with scars/lesions was further subdivided into two groups according to the type of the ocular manifestation observed: primary (n = 120) or recurrent (n = 28). Genotyping of the MICA and HLA alleles was performed by the polymerase chain reaction-sequence specific oligonucleotide technique (PCR-SSO; One Lambda®) and the MICA-129 polymorphism (rs1051792) was identified by nested polymerase chain reaction (PCR-RFLP). Significant associations involving MICA polymorphisms were not found. Although the MICA*002~HLA-B*35 haplotype was associated with increased risk of developing ocular toxoplasmosis (P-value = 0.04; OR = 2.20; 95% CI = 1.05–4.60), and the MICA*008~HLA-C*07 haplotype was associated with protection against the development of manifestations of ocular toxoplasmosis (P-value = 0.009; OR: 0.44; 95% CI: 0.22–0.76), these associations were not statistically significant after adjusting for multiple comparisons. MICA polymorphisms do not appear to influence the development of ocular lesions in patients diagnosed with toxoplasmosis in this study population. PMID:26672749

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

    Directory of Open Access Journals (Sweden)

    Lineu Cesar Werneck

    2016-08-01

    Full Text Available ABSTRACT Objective 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. Methods 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. Results 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. Conclusions 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.

  19. KIR2DL2 enhances protective and detrimental HLA class I-mediated immunity in chronic viral infection.

    Directory of Open Access Journals (Sweden)

    Nafisa-Katrin Seich Al Basatena

    2011-10-01

    Full Text Available Killer cell immunoglobulin-like receptors (KIRs influence both innate and adaptive immunity. But while the role of KIRs in NK-mediated innate immunity is well-documented, the impact of KIRs on the T cell response in human disease is not known. Here we test the hypothesis that an individual's KIR genotype affects the efficiency of their HLA class I-mediated antiviral immune response and the outcome of viral infection. We show that, in two unrelated viral infections, hepatitis C virus and human T lymphotropic virus type 1, possession of the KIR2DL2 gene enhanced both protective and detrimental HLA class I-restricted anti-viral immunity. These results reveal a novel role for inhibitory KIRs. We conclude that inhibitory KIRs, in synergy with T cells, are a major determinant of the outcome of persistent viral infection.

  20. Susceptible and protective HLA class 1 alleles against dengue fever and dengue hemorrhagic fever patients in a Malaysian population.

    Directory of Open Access Journals (Sweden)

    Ramapraba Appanna

    Full Text Available BACKGROUND: The human leukocyte antigen alleles have been implicated as probable genetic markers in predicting the susceptibility and/or protection to severe manifestations of dengue virus (DENV infection. In this present study, we aimed to investigate for the first time, the genotype variants of HLA Class 1(-A and -B of DENV infected patients against healthy individuals in Malaysia. METHODOLOGY/PRINCIPAL FINDINGS: This study was carried out with 92 dengue disease patients and 95 healthy controls from three different ethnic groups (Malay, Chinese and Indian in Malaysia. All patients with clinical and laboratory confirmation of DENV infection were typed for the HLA-A and B loci, using polymerase chain reaction-sequence specific primer techniques. In our total population, a significant increase for HLA-B*53 (P = 0.042, Pc = 1.008 allele and a significant decrease for A*03 (P = 0.015, Pc = 0.18, OR = 5.23, 95% CI = 1.19-23.02 and B*18 (P = 0.017, Pc = 0.408 alleles were noted in DHF patients as compared to healthy donors. We also observed that in the Malay DHF patients, allele B*13 (P = 0.049, Pc = 1.176, OR = 0.18, 95% CI = 0.03-0.90 was present at a significantly higher frequency in this population while allele HLA-B*18 (P = 0.024, Pc = 0.576 was seen to be negatively associated with DHF. CONCLUSIONS/SIGNIFICANCE: These are the first findings on genetic polymorphisms in our population and we conclude that: (1 In our total population, HLA-B*53 probably involve in disease susceptibility, while the HLA-A*03 and HLA-B*18 may confer protection from progression to severe disease; (2 In the Malay population, HLA-B*13 and B*18 are probably associated in disease susceptibility and protection, respectively. These results could furnish as a valuable predictive tool to identify ethnically different individuals at risk and/or protection from severe forms of DENV infection and would provide valuable informations for the design of future dengue vaccine.

  1. Mandibular condyle dimensions in Peruvian patients with Class II and Class III skeletal patterns.

    Directory of Open Access Journals (Sweden)

    Hugo Zegarra-Baquerizo

    2017-10-01

    Full Text Available Objective: To compare condylar dimensions of young adults with Class II and Class III skeletal patterns using cone-beam computed tomography (CBCT. Materials and methods: 124 CBCTs from 18-30 year-old patients, divided into 2 groups according to skeletal patterns (Class II and Class III were evaluated. Skeletal patterns were classified by measuring the ANB angle of each patient. The anteroposterior diameter (A and P of the right and left mandibular condyle was assessed from a sagittal view by a line drawn from point A (anterior to P (posterior. The coronal plane allowed the evaluation of the medio-lateral diameter by drawing a line from point M (medium to L (lateral; all distances were measured in mm. Results: In Class II the A-P diameter was 9.06±1.33 and 8.86±1.56 for the right and left condyles respectively, in Class III these values were 8.71±1.2 and 8.84±1.42. In Class II the M-L diameter was 17.94±2.68 and 17.67±2.44 for the right and left condyles respectively, in Class III these values were 19.16±2.75 and 19.16±2.54. Conclusion: Class III M-L dimensions showed higher values than Class II, whereas these differences were minimal in A-P.

  2. Evaluating the Role of HLA-DM in MHC Class II-Peptide Association Reactions.

    Science.gov (United States)

    Yin, Liusong; Maben, Zachary J; Becerra, Aniuska; Stern, Lawrence J

    2015-07-15

    Ag presentation by MHC class II (MHC II) molecules to CD4(+) T cells plays a key role in the regulation of the adaptive immune response. Loading of antigenic peptides onto MHC II is catalyzed by HLA-DM (DM), a nonclassical MHC II molecule. The mechanism of DM-facilitated peptide loading is an outstanding problem in the field of Ag presentation. In this study, we systemically explored possible kinetic mechanisms for DM-catalyzed peptide association by measuring real-time peptide association kinetics using fluorescence polarization assays and comparing the experimental data with numerically modeled peptide association reactions. We found that DM does not facilitate peptide association by stabilizing peptide-free MHC II against aggregation. Moreover, DM does not promote transition of an inactive peptide-averse conformation of MHC II to an active peptide-receptive conformation. Instead, DM forms an intermediate with MHC II that binds peptide with faster kinetics than MHC II in the absence of DM. In the absence of peptides, interaction of MHC II with DM leads to inactivation and formation of a peptide-averse form. This study provides novel insights into how DM efficiently catalyzes peptide loading during Ag presentation. Copyright © 2015 by The American Association of Immunologists, Inc.

  3. Do HLA class II genes protect against pulmonary tuberculosis? A systematic review and meta-analysis.

    Science.gov (United States)

    Oliveira-Cortez, A; Melo, A C; Chaves, V E; Condino-Neto, A; Camargos, P

    2016-10-01

    Pulmonary tuberculosis (PTB) develops by a complex combination of environmental, immunological and socioeconomic factors and genetic susceptibility. The human leukocyte antigen (HLA) is the most polymorphic biological system and plays an essential role in the immune response against PTB. The aim of this study was to carry out a systematic review and meta-analysis evaluating the relationship between HLA-DRB1, HLA-DQB1 and HLA-DQA1 gene polymorphisms as possible risk or protective factors for PTB. A systematic search of the PubMed and Scopus databases was conducted following the guidelines described in the PRISMA statement. Fifty-six alleles were included in the meta-analysis. In the total pooled results, HLA-DRB1*08:03 (OR 1.95, CI 1.29-2.96), HLA-DQB1*06:01 (OR 1.78, CI 1.39-2.28), HLA-DQB1*06:09 (OR 2.27, 95 % CI 1.04-4.96) and HLA-DQA1*01:01 (OR 2.12, CI 1.11-4.03) genes were related to higher susceptibility to PTB. Conversely, the presence of the genes HLA-DRB1*07:01 (OR 0.74, CI 0.56-0.97), HLA-DQB1*03:01 (OR 0.77, CI 0.61-0.97), HLA-DQB1*04:02 (OR 0.57, CI 0.39-0.83), HLA-DQA1*04:01 (OR 0.50, CI 0.26-0.95) and HLA-DQA1*05:01 (OR 0.66, CI 0.48-0.92) demonstrated protection against PTB. In an analysis by ethnic subgroups, we found more genetic associations in Caucasians than in Asians. These findings suggest that HLAs may be used as markers for acquisition and development of PTB. To strengthen PTB susceptibility/resistance, we recommend further multicentric studies in different geographic regions, with certainty of controls' exposure to M. tuberculosis by use of marker of latent or active PTB, with analysis stratified by ethnic groups, with descriptions of specific alleles and carrying out immunological functionality tests.

  4. Cranial-Base Morphology in Children with Class III Malocclusion

    Directory of Open Access Journals (Sweden)

    Hong-Po Chang

    2005-04-01

    Full Text Available The association between cranial-base morphology and Class III malocclusion is not fully understood. The purpose of this study was to investigate the morphologic characteristics of the cranial base in children with Class III malocclusion. Lateral cephalograms from 100 children with Class III malocclusion were compared with those from 100 subjects with normal occlusion. Ten landmarks on the cranial base were identified and digitized. Cephalometric assessment using seven angular and 18 linear measurements was performed by univariate and multivariate analyses. The results revealed that the greatest between-group differences occurred in the posterior cranial-base region. It was concluded that shortening and angular bending of the cranial base, and a diminished angle between the cranial base and mandibular ramus, may lead to Class III malocclusion associated with Class III facial morphology. The association between cranialbase morphology and other types of malocclusion needs clarification. Further study of regional changes in the cranial base, with geometric morphometric analysis, is warranted.

  5. Early treatment protocol for skeletal Class III malocclusion.

    Science.gov (United States)

    Oltramari-Navarro, Paula Vanessa Pedron; de Almeida, Renato Rodrigues; Conti, Ana Cláudia de Castro Ferreira; Navarro, Ricardo de Lima; de Almeida, Marcio Rodrigues; Fernandes, Leandra Sant'Anna Ferreira Parron

    2013-01-01

    Skeletal Class III malocclusion, with its unpredictable and unfavorable nature, has been characterized by a growth pattern with doubtful prognosis regarding orthodontic mechanics, even when performed early. For a long time, Class III malocclusion was regarded as a synonym of mandibular prognathism, regardless of the affected skeletal structures. Mandibular growth, essentially determined by genetic factors, could barely be controlled by early orthodontic interventions. Therefore, the treatment choice was to wait for the patient to grow, and then make an orthodontic intervention associated with an orthognathic surgery. Maxillary involvement in the etiology of Class III malocclusion was conclusive to change orthodontic therapeutics. Maxillary intramembranous growth has a better response to orthopedic treatment, based on growth control and redirection, thus contributing for early intervention success. In several cases, excellent results have been achieved with rapid maxillary expansion and protraction. The aim of this study was to describe and discuss the treatment of a patient with Class III malocclusion, whose treatment planning comprised two phases: interceptive (mechanical orthopedic appliances) and comprehensive (fixed orthodontic appliance). The results of this case showed that Class III malocclusion should be intercepted as early as possible to permit growth redirection, mainly when the maxilla is the primary etiologic factor or dental and/or functional factors are involved. Diagnosis, treatment planning and prognosis depend on patient age, growth potential and severity of malocclusion. Early intervention, adequate indication of appliances, and patient compliance are key factors for good outcomes.

  6. Strong HLA class I--restricted T cell responses in dengue hemorrhagic fever: a double-edged sword?

    Science.gov (United States)

    Loke, H; Bethell, D B; Phuong, C X; Dung, M; Schneider, J; White, N J; Day, N P; Farrar, J; Hill, A V

    2001-12-01

    Dengue is an increasingly important cause of morbidity and mortality in the tropics, but vaccine development has been impeded by a poor understanding of disease pathogenesis and, in particular, of immunologic enhancement. In a large case-control study of Vietnamese patients with dengue hemorrhagic fever (DHF), variation at the HLA-A locus was significantly associated with susceptibility to DHF (P=.02), and specific HLA-A susceptibility and resistance alleles were identified. HLA-A-specific epitopes were predicted from binding motifs, and ELISPOT analyses of patients with DHF revealed high frequencies of circulating CD8 T lymphocytes that recognized both serotype-specific and -cross-reactive dengue virus epitopes. Thus, strong CD8 T cell responses are induced by natural dengue virus infection, and HLA class I genetic variation is a risk factor for DHF. These genetic and immunologic data support both protective and pathogenic roles for dengue virus-specific CD8 T cell responses in severe disease. The potentially pathogenic role of serotype-cross-reactive CD8 T cells poses yet another obstacle to successful dengue vaccine development.

  7. HLA class I variation in Iranian Lur and Kurd populations: high haplotype and allotype diversity with an abundance of KIR ligands.

    Science.gov (United States)

    Ashouri, E; Norman, P J; Guethlein, L A; Han, A S; Nemat-Gorgani, N; Norberg, S J; Ghaderi, A; Parham, P

    2016-09-01

    HLA-A, -B and -C alleles of 285 individuals, representing three Iranian Lur populations and one Iranian Kurd population were sequenced completely, yielding human leukocyte antigen (HLA) class I genotypes at high resolution and filling four fields of the official HLA nomenclature. Each population has 87-99 alleles, evenly distributed between the three HLA class I genes, 145 alleles being identified in total. These alleles were already known, named and deposited in the HLA database. The alleles form 316 different HLA A-B-C haplotypes, with each population having between 80 and 112 haplotypes. The four Iranian populations form a related group that is distinguished from other populations, including other Iranians. All four KIR ligands - the A3/11, Bw4, C1 and C2 epitopes - are well represented, particularly Bw4, which is carried by three high-frequency allotypes: HLA-A*24:02, HLA-A*32:01 and HLA-B*51:01. In the Lur and Kurd populations, between 82% and 94% of individuals have the Bw4 epitope, the ligand for KIR3DL1. HLA-B*51:01 is likely of Neandertal origin and associated with Behcet's disease, also known as the Silk Road disease. The Lordegan Lur have the highest frequency of HLA-B*51:01 in the world. This allele is present on 46 Lur and Kurd haplotypes. Present at lower frequency is HLA-B*51:08, which is also associated with Behcet's disease. In the four Iranian populations, 31 haplotypes encode both Bw4(+) HLA-A and Bw4(+) HLA-B, a dual combination of Bw4 epitopes that is relatively rare in other populations, worldwide. This study both demonstrates and emphasizes the value of studying HLA class I polymorphism at highest resolution in anthropologically well-defined populations. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  8. Construction of full-length Japanese reference panel of class I HLA genes with single-molecule, real-time sequencing.

    Science.gov (United States)

    Mimori, Takahiro; Yasuda, Jun; Kuroki, Yoko; Shibata, Tomoko F; Katsuoka, Fumiki; Saito, Sakae; Nariai, Naoki; Ono, Akira; Nakai-Inagaki, Naomi; Misawa, Kazuharu; Tateno, Keiko; Kawai, Yosuke; Fuse, Nobuo; Hozawa, Atsushi; Kuriyama, Shinichi; Sugawara, Junichi; Minegishi, Naoko; Suzuki, Kichiya; Kinoshita, Kengo; Nagasaki, Masao; Yamamoto, Masayuki

    2018-01-19

    Human leukocyte antigen (HLA) is a gene complex known for its exceptional diversity across populations, importance in organ and blood stem cell transplantation, and associations of specific alleles with various diseases. We constructed a Japanese reference panel of class I HLA genes (ToMMo HLA panel), comprising a distinct set of HLA-A, HLA-B, HLA-C, and HLA-H alleles, by single-molecule, real-time (SMRT) sequencing of 208 individuals included in the 1070 whole-genome Japanese reference panel (1KJPN). For high-quality allele reconstruction, we developed a novel pipeline, Primer-Separation Assembly and Refinement Pipeline (PSARP), in which the SMRT sequencing and additional short-read data were used. The panel consisted of 139 alleles, which were all extended from known IPD-IMGT/HLA sequences, contained 40 with novel variants, and captured more than 96.5% of allelic diversity in 1KJPN. These newly available sequences would be important resources for research and clinical applications including high-resolution HLA typing, genetic association studies, and analyzes of cis-regulatory elements.

  9. Diagnosis and Treatment of Pseudo-Class III Malocclusion

    Science.gov (United States)

    Reyes, Ariel; Serret, Luis; Peguero, Marcos; Tanaka, Orlando

    2014-01-01

    Pseudo-Class III malocclusion is characterized by the presence of an anterior crossbite due to a forward functional displacement of the mandible; in most cases, the maxillary incisors present some degree of retroclination, and the mandibular incisors are proclined. Various types of appliances have been described in the literature for the early treatment of pseudo-Class III malocclusion. The objectives of this paper are to demonstrate the importance of making the differential diagnosis between a skeletal and a pseudo-Class III malocclusion and to describe the correction of an anterior crossbite. The association of maxillary expansion and a 2 × 4 appliance can successfully be used to correct anterior crossbites. PMID:25525526

  10. Diagnosis and Treatment of Pseudo-Class III Malocclusion

    Directory of Open Access Journals (Sweden)

    Ariel Reyes

    2014-01-01

    Full Text Available Pseudo-Class III malocclusion is characterized by the presence of an anterior crossbite due to a forward functional displacement of the mandible; in most cases, the maxillary incisors present some degree of retroclination, and the mandibular incisors are proclined. Various types of appliances have been described in the literature for the early treatment of pseudo-Class III malocclusion. The objectives of this paper are to demonstrate the importance of making the differential diagnosis between a skeletal and a pseudo-Class III malocclusion and to describe the correction of an anterior crossbite. The association of maxillary expansion and a 2 × 4 appliance can successfully be used to correct anterior crossbites.

  11. A long peptide from MELOE-1 contains multiple HLA class II T cell epitopes in addition to the HLA-A*0201 epitope: an attractive candidate for melanoma vaccination.

    Science.gov (United States)

    Rogel, Anne; Vignard, Virginie; Bobinet, Mathilde; Labarriere, Nathalie; Lang, François

    2011-03-01

    CD4(+) T cells contribute importantly to the antitumor T cell response, and thus, long peptides comprising CD4 and CD8 epitopes may be efficient cancer vaccines. We have previously identified an overexpressed antigen in melanoma, MELOE-1, presenting a CD8(+) T cell epitope, MELOE-1(36-44), in the HLA-A*0201 context. A T cell repertoire against this epitope is present in HLA-A*0201+ healthy subjects and melanoma patients and the adjuvant injection of TIL containing MELOE-1 specific CD8(+) T cells to melanoma patients was shown to be beneficial. In this study, we looked for CD4(+) T cell epitopes in the vicinity of the HLA-A*0201 epitope. Stimulation of PBMC from healthy subjects with MELOE-1(26-46) revealed CD4 responses in multiple HLA contexts and by cloning responsive CD4(+) T cells, we identified one HLA-DRβ1*1101-restricted and one HLA-DQβ1*0603-restricted epitope. We showed that the two epitopes could be efficiently presented to CD4(+) T cells by MELOE-1-loaded dendritic cells but not by MELOE-1+ melanoma cell-lines. Finally, we showed that the long peptide MELOE-1(22-46), containing the two optimal class II epitopes and the HLA-A*0201 epitope, was efficiently processed by DC to stimulate CD4(+) and CD8(+) T cell responses in vitro, making it a potential candidate for melanoma vaccination.

  12. Soluble monomers, dimers and HLA-G-expressing extracellular vesicles: the three dimensions of structural complexity to use HLA-G as a clinical biomarker.

    Science.gov (United States)

    Nardi, F da Silva; König, L; Wagner, B; Giebel, B; Santos Manvailer, L F; Rebmann, V

    2016-09-01

    The HLA-G molecule belongs to the family of nonclassical human leukocyte antigen (HLA) class I. At variance to classical HLA class I, HLA-G displays (i) a low number of nucleotide variations within the coding region, (ii) a high structural diversity, (iii) a restricted peptide repertoire, (iv) a limited tissue distribution and (v) strong immune-suppressive properties. The physiological HLA-G surface expression is restricted to the maternal-fetal interface and to immune-privileged adult tissues. Soluble forms of HLA-G (sHLA-G) are detectable in various body fluids. Cellular activation and pathological processes are associated with an aberrant or a neo-expression of HLA-G/sHLA-G. Functionally, HLA-G and its secreted forms are considered to be key players in the induction of short- and long-term tolerance. Thus, its unique expression profile and tolerance-inducing functions render HLA-G/sHLA-G an attractive biomarker to monitor the systemic health/disease status and disease activity/progression for clinical approaches in disease management and treatments. Here, we place emphasis on (i) the current status of the tolerance-inducing functions by HLA-G/sHLA-G, (ii) the current complexity to implement this molecule as a meaningful clinical biomarker regarding the three dimensions of structural diversity (monomers, dimers and HLA-G-expressing extracellular vesicles) with its functional implications, and (iii) novel and future approaches to detect and quantify sHLA-G structures and functions. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  13. [New class III antiarrhythmic drugs for treatment of atrial fibrillation].

    Science.gov (United States)

    Maĭkov, E B

    2012-01-01

    Last two decades have been dedicated to intensive search for new class III antiarrhythmic drugs, especially for atrial fibrillation. Here we present a review of the status this problem. Influence on transmembranous ion currents and mechanisms of antiarrhythmic action are described. Results of experimental and clinical studies are reviewed. Possible perspectives of newest atrial-selective medications are discussed. Russia's class III antiarrhythmic drugs are of special interest of the article. First data on efficacy and safety of newest agent niferidil are presented. This drug undergoes clinical testing at present time.

  14. Conservative treatment of Angle Class III malocclusion with anterior crossbite

    Directory of Open Access Journals (Sweden)

    João Hélder Ferreira de Aguiar

    2015-08-01

    Full Text Available Angle Class III malocclusion is characterized by anteroposterior dental discrepancy which might be associated or not with skeletal changes. Class III molar relationship is associated with vertical or lingually tipped mandibular incisors and a usually concave profile. These characteristics seriously affect facial esthetics and most frequently are the reason why patients seek orthodontic treatment. This case was presented to the committee of the Brazilian Board of Orthodontics and Facial Orthopedics (BBO as part of the requisites to become a BBO Diplomate.

  15. 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

  16. HLA Class Ib Molecules and Immune Cells in Pregnancy and Preeclampsia

    DEFF Research Database (Denmark)

    Djurisic, Snezana; Hviid, Thomas Vauvert F

    2014-01-01

    Despite decades of research, the highly prevalent pregnancy complication preeclampsia, "the disease of theories," has remained an enigma. Indeed, the etiology of preeclampsia is largely unknown. A compiling amount of studies indicates that the pathological basis involves a complex array of genetic...... predisposition and immunological maladaptation, and that a contribution from the mother, the father, and the fetus is likely to be important. The Human Leukocyte Antigen (HLA)-G is an increasing focus of research in relation to preeclampsia. The HLA-G molecule is primarily expressed by the extravillous...... of HLA-G, and, in some studies, with preeclampsia. In this review, a genetic contribution from the mother, the father, and the fetus, together with the presence and function of various immune cells of relevance in pregnancy are reviewed in relation to HLA-G and preeclampsia....

  17. 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

    activity correlated with T cell responsiveness, alloantigen-primed T cells were activated with immobilized class II-specific mAb or soluble superantigen. Both HLA-DR mAb-stimulated T cells and enterotoxin-treated T cells proliferated strongly in response to co-stimulation by a combination of CD28 receptor...... engagement and PMA addition. In addition, superantigen-induced growth was induced by CD28 receptor ligation with antibody or the B7 counter-receptor expressed on Chinese hamster ovary cells. Taken together, these results indicate that class II molecules expressed on activated T cells are directly coupled...

  18. Associations between HLA class I and cytochrome P450 2C9 genetic polymorphisms and phenytoin-related severe cutaneous adverse reactions in a Thai population.

    Science.gov (United States)

    Tassaneeyakul, Wichittra; Prabmeechai, Napat; Sukasem, Chonlaphat; Kongpan, Thachanan; Konyoung, Parinya; Chumworathayi, Pansu; Tiamkao, Somsak; Khunarkornsiri, Usanee; Kulkantrakorn, Kongkiat; Saksit, Niwat; Nakkam, Nontaya; Satapornpong, Patompong; Vannaprasaht, Suda; Sangviroon, Alisara; Mahasirimongkol, Surakameth; Wichukchinda, Nuanjun; Rerkpattanapipat, Ticha; Tassaneeyakul, Wongwiwat

    2016-05-01

    Phenytoin is one of the most common causative drugs of several types of severe cutaneous adverse reactions (SCAR) such as Stevens-Johnson syndrome (SJS), toxic epidermal necrolysis (TEN), and drug reactions with eosinophilia and systemic symptoms (DRESS). Genetic polymorphisms of the human leukocyte antigens (HLA) and cytochromes P450 (CYP) have been proposed as key elements for the susceptibility to phenytoin-related SCAR in certain ethnicities. This study investigated the associations between the genetic polymorphisms of HLA class I and CYP2C9 and phenytoin-related SCAR in a Thai population. Sixty phenytoin-related SCAR (i.e. 39 SJS/TEN and 21 DRESS) and 92 phenytoin-tolerant patients were enrolled in the study. The genotypes of HLA class I and CYP2C9 were determined. Six HLA alleles including HLA-A*33:03, HLA-B*38:02, HLA-B*51:01, HLA-B*56:02, HLA-B*58:01, and HLA-C*14:02 were significantly associated with phenytoin-related SJS/TEN, whereas only the HLA-B*51:01 was significantly associated with phenytoin-related DRESS. The odds ratios of phenytoin-related SJS/TEN in the patients who carried one of these alleles ranged from 4- to 10-fold. The frequencies of patients who carried the HLA-B*15:02 in the SJS/TEN (12.82%) or the DRESS (9.52%) groups were not significantly different from that of the controls (14.13%). The higher risk of phenytoin-related SJS/TEN was observed in the patients with CYP2C9*3 (odds ratio=4.30, 95% confidence interval=1.41-13.09, Pcaused by phenytoin was significantly associated with the HLA-B*15:02. The CYP2C9*3 variant was significantly associated with phenytoin-related SJS/TEN, but not DRESS. Certain alleles of HLA, particularly HLA-B*56:02, were significantly associated with phenytoin-related SCAR in the study population.

  19. [KIR-HLA class i and pulmonary tuberculosis in the Amerindian population in Chaco, Argentina].

    Science.gov (United States)

    Habegger de Sorrentino, Alicia; Pardo, Raúl; Marinic, Karina; Duarte, Sonia C; Lotero, Carlos

    2014-11-01

    The susceptibility to pulmonary tuberculosis (TB) is multifactorial, thus genetic factors such as HLA and immunoglobulins-like killer receptors (KIR) could be predisposed to the development of the disease. Aim To evaluate whether any HLA classi allele and its combination with KIR could be related to the development of TB in the Wichi Amerindian community in north-eastern Argentina. A cohort study was conducted that included 18 families, 35 individuals affected with TB, 84 cohabiting families, and 63 controls of the same ethnic group. A and B loci of HLA classi were typed by generic PCR followed by reverse hybridization (Dynal), locus C by PCR-SSOP. KIR receptors were studied using sequence specific PCR. There was a highly significant association with allele B*35:19/47 in TB vs. household contacts [Pc=0.0051] and vs. controls [Pc=0.0033], and with allele HLA-C*03 in TB vs. household contacts [Pc=0.014] and vs. controls [Pc=0.0033]. KIR receptors had shown increased KIR2DL3/KIR2DL3 frequency in combination with the C1 group of HLA-C (P=.018). HLA-C*03 belongs to C1 group, and this combination could have a strong inhibitory action on the infected cell. HLA-B35:19/47-C*03 haplotype could be a susceptibility factor to TB and KIR2DL3-HLA-C1 combination have an inhibitory capacity on NK cells, and might contribute to the course of the infection by Mycobacterium tuberculosis. Copyright © 2013 Elsevier España, S.L.U. y Sociedad Española de Enfermedades Infecciosas y Microbiología Clínica. All rights reserved.

  20. Regulatory polymorphisms modulate the expression of HLA class II molecules and promote autoimmunity

    Science.gov (United States)

    Raj, Prithvi; Rai, Ekta; Song, Ran; Khan, Shaheen; Wakeland, Benjamin E; Viswanathan, Kasthuribai; Arana, Carlos; Liang, Chaoying; Zhang, Bo; Dozmorov, Igor; Carr-Johnson, Ferdicia; Mitrovic, Mitja; Wiley, Graham B; Kelly, Jennifer A; Lauwerys, Bernard R; Olsen, Nancy J; Cotsapas, Chris; Garcia, Christine K; Wise, Carol A; Harley, John B; Nath, Swapan K; James, Judith A; Jacob, Chaim O; Tsao, Betty P; Pasare, Chandrashekhar; Karp, David R; Li, Quan Zhen; Gaffney, Patrick M; Wakeland, Edward K

    2016-01-01

    Targeted sequencing of sixteen SLE risk loci among 1349 Caucasian cases and controls produced a comprehensive dataset of the variations causing susceptibility to systemic lupus erythematosus (SLE). Two independent disease association signals in the HLA-D region identified two regulatory regions containing 3562 polymorphisms that modified thirty-seven transcription factor binding sites. These extensive functional variations are a new and potent facet of HLA polymorphism. Variations modifying the consensus binding motifs of IRF4 and CTCF in the XL9 regulatory complex modified the transcription of HLA-DRB1, HLA-DQA1 and HLA-DQB1 in a chromosome-specific manner, resulting in a 2.5-fold increase in the surface expression of HLA-DR and DQ molecules on dendritic cells with SLE risk genotypes, which increases to over 4-fold after stimulation. Similar analyses of fifteen other SLE risk loci identified 1206 functional variants tightly linked with disease-associated SNPs and demonstrated that common disease alleles contain multiple causal variants modulating multiple immune system genes. DOI: http://dx.doi.org/10.7554/eLife.12089.001 PMID:26880555

  1. High-sensitivity HLA class I peptidome analysis enables a precise definition of peptide motifs and the identification of peptides from cell lines and patients' sera.

    Science.gov (United States)

    Ritz, Danilo; Gloger, Andreas; Weide, Benjamin; Garbe, Claus; Neri, Dario; Fugmann, Tim

    2016-05-01

    The characterization of peptides bound to human leukocyte antigen (HLA) class I is of fundamental importance for understanding CD8+ T cell-driven immunological processes and for the development of immunomodulatory therapeutic strategies. However, until now, the mass spectrometric analysis of HLA-bound peptides has typically required billions of cells, still resulting in relatively few high-confidence peptide identifications. Capitalizing on the recent developments in mass spectrometry and bioinformatics, we have implemented a methodology for the efficient recovery of acid-eluted HLA peptides after purification with the pan-reactive antibody W6/32 and have identified a total of 27 862 unique peptides with high confidence (1% false discovery rate) from five human cancer cell lines. More than 93% of the identified peptides were eight to 11 amino acids in length and contained signatures that were in excellent agreement with published HLA binding motifs. Furthermore, by purifying soluble HLA class I complexes (sHLA) from sera of melanoma patients, up to 972 high-confidence peptides could be identified, including melanoma-associated antigens already described in the literature. Knowledge of the HLA class I peptidome should facilitate multiplex tetramer technology-based characterization of T cells, and allow the development of patient selection, stratification and immunomodulatory therapeutic strategies. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  2. Extracellular domains of CD8α and CD8ß subunits are sufficient for HLA class I restricted helper functions of TCR-engineered CD4(+ T cells.

    Directory of Open Access Journals (Sweden)

    Marleen M van Loenen

    Full Text Available By gene transfer of HLA-class I restricted T-cell receptors (TCRs (HLA-I-TCR into CD8(+ as well as CD4(+ T-cells, both effector T-cells as well as helper T-cells can be generated. Since most HLA-I-TCRs function best in the presence of the CD8 co-receptor, the CD8αß molecule has to be co-transferred into the CD4(+ T-cells to engineer optimal helper T-cells. In this study, we set out to determine the minimal part of CD8αβ needed for optimal co-receptor function in HLA-I-TCR transduced CD4(+ T-cells. For this purpose, we transduced human peripheral blood derived CD4(+ T-cells with several HLA-class I restricted TCRs either with or without co-transfer of different CD8 subunits. We demonstrate that the co-transduced CD8αβ co-receptor in HLA-I-TCR transduced CD4(+ T-cells behaves as an adhesion molecule, since for optimal antigen-specific HLA class I restricted CD4(+ T-cell reactivity the extracellular domains of the CD8α and ß subunits are sufficient.

  3. Introduction of a point mutation into an HLA class I single-chain trimer induces enhancement of CTL priming and antitumor immunity

    Directory of Open Access Journals (Sweden)

    Masanori Matsui

    2014-01-01

    Full Text Available We previously discovered one particular HLA-A*02:01 mutant that enhanced peptide-specific cytotoxic T lymphocyte (CTL recognition in vitro compared to wild-type HLA-A*02:01. This mutant contains a single amino acid substitution from histidine to leucine at position 74 (H74L that is located in the peptide-binding groove. To investigate the effect of the H74L mutation on the in vivo CTL priming, we took advantage of the technology of the HLA class I single-chain trimer (SCT in which three components involving a peptide, β2 microglobulin and the HLA class I heavy chain are joined together via flexible linkers. We generated recombinant adenovirus expressing SCT comprised influenza A matrix protein (FMP-derived peptide, β2 microglobulin and the H74L heavy chain. HLA-A*02:01 transgenic mice were immunized with the adenovirus, and the induction of peptide-specific CTLs and antitumor immunity was investigated. It was clearly shown that the H74L mutation enabled the HLA-A*02:01 SCT molecule to dramatically enhance both in vivo priming of FMP-specific CTLs and protection against a lethal challenge of tumor cells expressing FMP. These data present the first evidence that a simple point mutation in the HLA class I heavy chain of SCT is beneficial for improving CTL-based immunotherapy and prophylaxis to control tumors.

  4. 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...... 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). CONCLUSION: Maternal carriage...

  5. Reassessing Pre-market Regulation of Class III Medical Devices

    OpenAIRE

    Zollinger, Geri

    2003-01-01

    Regulation of medical devices has evolved over the past twenty-five years. Initially, Congress created a regime where the safety and efficacy of all medical devices would be reviewed to varying degrees, depending on the risk posed by the device. Class III devices, the most dangerous class of devices, were to each have a safety and efficacy review. To permit new market entrants on similar grounds as those marketing devices prior to the 1976 Amendments, Congress also created a premarket notific...

  6. Molecular typing for HLA class I using ARMS-PCR: further developments following the 12th International Histocompatibility Workshop.

    Science.gov (United States)

    Tonks, S; Marsh, S G; Bunce, M; Bodmer, J G

    1999-02-01

    Molecular typing for HLA class I was introduced in the 12th International Histocompatibility Workshop. Following a pilot study using three methods, sequence specific oligotyping (SSO), reverse dot blot and amplification refractory mutation system (ARMS)-PCR, the ARMS-PCR method was selected for use. A great advantage of an ARMS-PCR method is that, unlike the other two methods, it can determine whether sequence motifs are in cis or in trans, as ARMS-PCR detects two cis located motifs per reaction using forward and reverse sequence specific primers. Resolution was designed to be low to medium level for HLA-A, -B and -C alleles. Two hundred and fifty class I kits and 83 HLA-A2 subtyping kits were distributed. The A2 subtyping kit used a two round nested PCR system to identify all of the A2 alleles known at the time. Typing results on control DNA samples distributed with both the kits showed a very satisfactory performance. Since the 12th Workshop, the kits have been developed with the addition of new primers and primer mixes to increase the resolution of the test.

  7. Recognition of naturally processed and ovarian cancer reactive CD8+ T cell epitopes within a promiscuous HLA class II T-helper region of NY-ESO-1.

    Science.gov (United States)

    Matsuzaki, Junko; Qian, Feng; Luescher, Immanuel; Lele, Shashikant; Ritter, Gerd; Shrikant, Protul A; Gnjatic, Sacha; Old, Lloyd J; Odunsi, Kunle

    2008-08-01

    NY-ESO-1 is frequently expressed in epithelial ovarian cancer (EOC) and elicits spontaneous humoral and cellular immune responses in a proportion of EOC patients. The identification of NY-ESO-1 peptide epitopes with dual HLA-class I and class II specificities might be useful in vaccination strategies for generating cognate CD4+ T cell help to augment CD8+ T cell responses. Here, we describe two novel NY-ESO-1-derived MHC class I epitopes from EOC patients with spontaneous humoral immune response to NY-ESO-1. CD8+ T cells derived from NY-ESO-1 seropositive EOC patients were presensitized with a recombinant adenovirus encoding NY-ESO-1or pooled overlapping peptides. These epitopes, ESO127-136 presented by HLA-A68 molecule, and ESO127-135 restricted by HLA-Cw15 allele, are located within ESO119-143, a promiscuous HLA-class II region containing epitopes that bind to multiple HLA-DR alleles. The novel epitopes were naturally processed by APC or naturally presented by tumor cell lines. In addition, these epitopes induced NY-ESO-1-specific CTL in NY-ESO-1 seropositive EOC patients. Together, the results indicate that ESO119-143 epitope has dual HLA classes I and II specificities, and represents a potential vaccine candidate in a large number of cancer patients.

  8. Activation of ERα signaling differentially modulates IFN-γ induced HLA-class II expression in breast cancer cells.

    Directory of Open Access Journals (Sweden)

    Ahmed A Mostafa

    Full Text Available The coordinate regulation of HLA class II (HLA-II is controlled by the class II transactivator, CIITA, and is crucial for the development of anti-tumor immunity. HLA-II in breast carcinoma is associated with increased IFN-γ levels, reduced expression of the estrogen receptor (ER and reduced age at diagnosis. Here, we tested the hypothesis that estradiol (E₂ and ERα signaling contribute to the regulation of IFN-γ inducible HLA-II in breast cancer cells. Using a panel of established ER⁻ and ER⁺ breast cancer cell lines, we showed that E₂ attenuated HLA-DR in two ER⁺ lines (MCF-7 and BT-474, but not in T47D, while it augmented expression in ER⁻ lines, SK-BR-3 and MDA-MB-231. To further study the mechanism(s, we used paired transfectants: ERα⁺ MC2 (MDA-MB-231 c10A transfected with the wild type ERα gene and ERα⁻ VC5 (MDA-MB-231 c10A transfected with the empty vector, treated or not with E₂ and IFN-γ. HLA-II and CIITA were severely reduced in MC2 compared to VC5 and were further exacerbated by E₂ treatment. Reduced expression occurred at the level of the IFN-γ inducible CIITA promoter IV. The anti-estrogen ICI 182,780 and gene silencing with ESR1 siRNA reversed the E2 inhibitory effects, signifying an antagonistic role for activated ERα on CIITA pIV activity. Moreover, STAT1 signaling, necessary for CIITA pIV activation, and selected STAT1 regulated genes were variably downregulated by E₂ in transfected and endogenous ERα positive breast cancer cells, whereas STAT1 signaling was noticeably augmented in ERα⁻ breast cancer cells. Collectively, these results imply immune escape mechanisms in ERα⁺ breast cancer may be facilitated through an ERα suppressive mechanism on IFN-γ signaling.

  9. Antibodies against a class II HLA-peptide complex raised by active immunization of mice with antigen mimicking peptides

    DEFF Research Database (Denmark)

    Dam-Tuxen, R; Riise, Erik Skjold

    2009-01-01

    Multiple sclerosis (MS) is an autoimmune disease linked to the human leucocyte antigen (HLA) class II genes DRB1*1501, DRB5*0101 and DQB1*0602. T cells reactive towards the DRB1*1501 in complex with various peptides derived from myelin basic protein (MBP), which is the major component of myelin......, have been found in the peripheral blood of MS patients. These autoreactive T cells are believed to play a role in the pathogenesis of MS. In this article, antibodies against the HLA complex DR2b (DRA1*0101/DRB1*1501) in complex with the MBP-derived peptide MBP(85-99) have been generated by immunization...

  10. 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.)

  11. Expression of class II major histocompatibility complex antigens (HLA-DR) and lymphocyte subset immunotyping in chronic pulmonary transplant rejection.

    Science.gov (United States)

    Hasegawa, S; Ockner, D M; Ritter, J H; Patterson, G A; Trulock, E P; Cooper, J D; Wick, M R

    1995-05-01

    Currently, the bronchiolitis obliterans syndrome (BOS) of chronic airway rejection represents the most significant obstacle to the long-term function of isolated pulmonary allografts in humans. Between 20% and 30% of recipients are affected by this condition. To define the possible pathogenetic role of altered expression of class II major histocompatibility complex antigens (ie, HLA-DR) in BOS, the authors studied well-characterized examples of this process immunohistologically. Eleven BOS specimens were compared with seven controls, represented by allografts with no pathologic abnormalities taken from patients with normal posttransplant respiratory function, as well as 14 biopsies showing acute rejection. In addition, immunophenotypic subtyping of lymphocytes in all specimens was undertaken. Control tissues exhibited variable but weak expression of HLA-DR in bronchiolar epithelium and alveolar pneumocytes. In comparison, immunostaining for class II major histocompatibility complex antigens in BOS showed no statistically significant differences, whereas the 14 examples of acute rejection manifested intense HLA-DR expression in epithelia and endothelial cells. The numbers of intrabronchiolar and peribronchiolar lymphocytes were clearly higher in both acute rejection and BOS than in controls, but these cells differed in lineage in the two rejection states. Acute rejection showed an obvious preponderance of CD43-positive T lymphocytes, whereas lymphoid cells in BOS were a relatively equal mixture of CD20-positive B cells and CD43-positive T cells. Moreover, incipient peribronchiolar B-cell follicles were observed in BOS. Natural killer (CD57-positive) lymphocytes were rare in all specimens. These data suggest that alterations in HLA-DR expression probably do not play a central role in the genesis of BOS, as they do in acute rejection. In contrast, the results of lymphocyte immunophenotyping and correlative histologic findings in BOS suggest that both T cells and B

  12. Frequency of HLA alleles class I and II in a cohort of northwestern Colombian patients with spondyloarthritis Frecuencia de alelos HLA de clase I y II en una cohorte de pacientes del noroccidente colombiano con espondiloartritis

    Directory of Open Access Journals (Sweden)

    Luis F ernando Pinto

    2011-09-01

    Full Text Available Introduction. Spondyloarthritis are chronic rheumatic diseases that affect the axial skeleton and peripheral joints, with several extra-articular manifestations. The association with HLA-B27 remains one of the strongest links known between these entities and the major histocompatibility complex, but the global distribution of HLA-B27 varies considerably and associations with non-HLA-B27 genes have been described.
    Objective. To determine the frequency of HLA class I and II in northwestern Colombian patients with spondyloarthritis and their frequency in the clinical and radiological specific manifestations
    Materials and methods. We conducted a descriptive, observational, cross-sectional, retrospective and prospective study in 56 Colombian patients with spondyloarthritis between 2005 and 2008. Alleles were identified for the loci HLA class I and II (HLA-B; HLADQB1 and HLADRB. We analyzed the frequency of these alleles in the axial, peripheral, extraarticular and radiological manifestations.
    Results. We found a low frequency of HLA-B27 in the whole population (50%, but it was the most frequent allele, together with HLA.DRB4*01 (35.7% and HLA-DQB1*0501 (28.6% in all the patients and d in each one of the clinical and radiological manifestations. We highlight the high frequency of HLA-B27 and HLA-DRB4*01 (64.3% in patients with dactylitis. These findings, until it is known, have not been reported previously.
    Conclusion. The alleles: HLA-B27, HLA-DRB4 * 01 and HLA-DQB1 * 0501 were common in the different subtypes of spondyloarthritis and are frequent in the specific clinical axial, peripheral and extraarticular clinical manifestations, as well as radiological sacroiliitis.
    Introducción. Las espondiloartritis son enfermedades reumatológicas crónicas que afectan el esqueleto axial y las articulaciones periféricas, con varias manifestaciones extraarticulares. La asociación con HLA-B27 sigue siendo uno de los vínculos m

  13. 25 CFR 502.4 - Class III gaming.

    Science.gov (United States)

    2010-04-01

    .... 1171(a)(1) and electronic or electromechanical facsimiles of any game of chance; (c) Any sports betting... 25 Indians 2 2010-04-01 2010-04-01 false Class III gaming. 502.4 Section 502.4 Indians NATIONAL INDIAN GAMING COMMISSION, DEPARTMENT OF THE INTERIOR GENERAL PROVISIONS DEFINITIONS OF THIS CHAPTER § 502...

  14. More than 150 novel variants of HLA class I genes detected in German Stem Cell Donor Registry and UCLA International Cell Exchange samples.

    Science.gov (United States)

    Balz, V; Krause, S; Fischer, J; Enczmann, J

    2018-01-08

    High throughput analysis using amplicon-based next-generation sequencing (NGS) of HLA class I genes in samples of registered stem cell donors of the German Stem Cell Donor Registry Düsseldorf revealed 151 novel variants. In addition, four new variants were identified in well-defined samples obtained from the UCLA International Cell Exchange program. New alleles included 37 HLA-A, 57 HLA-B, and 61 HLA-C variant alleles. All variants were confirmed by NGS of HLA-A, HLA-B, and HLA-C genes including the respective 5' and 3' untranslated regions as well as Sanger sequence analysis. Mainly, the variants encompass single nucleotide changes in intronic as well as exonic parts of the genes. We identified intronic variations in 114 new alleles, nonsynonymous nucleotide changes in 25 alleles, synonymous nucleotide changes in nine alleles, and three hybrid alleles. Four alleles carry exonic deletions or insertions resulting in frameshift of peptide translation. Two novel alleles of HLA-C were shown to result in splicing defects of the transcript. Two alleles showed exonic as well as intronic changes. Thirty-four of the new alleles were found in multiple samples. © 2018 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  15. Amino acid substitution at peptide-binding pockets of HLA class I molecules increases risk of severe acute GVHD and mortality

    Science.gov (United States)

    Wang, Tao; Haagenson, Michael; Spellman, Stephen R.; Askar, Medhat; Battiwalla, Minoo; Baxter-Lowe, Lee Ann; Bitan, Menachem; Fernandez-Viña, Marcelo; Gandhi, Manish; Jakubowski, Ann A.; Maiers, Martin; Marino, Susana R.; Marsh, Steven G. E.; Oudshoorn, Machteld; Palmer, Jeanne; Prasad, Vinod K.; Reddy, Vijay; Ringden, Olle; Saber, Wael; Santarone, Stella; Schultz, Kirk R.; Setterholm, Michelle; Trachtenberg, Elizabeth; Turner, E. Victoria; Woolfrey, Ann E.; Lee, Stephanie J.; Anasetti, Claudio

    2013-01-01

    HLA disparity has a negative impact on the outcomes of hematopoietic cell transplantation (HCT). We studied the independent impact of amino acid substitution (AAS) at peptide-binding positions 9, 99, 116, and 156, and killer immunoglobulin-like receptor binding position 77 of HLA-A, B, or C, on the risks for grade 3-4 acute graft-versus-host disease (GVHD), chronic GVHD, treatment-related mortality (TRM), relapse, and overall survival. In multivariate analysis, a mismatch at HLA-C position 116 was associated with increased risk for severe acute GVHD (hazard ratio [HR] = 1.45, 95% confidence interval [CI] = 1.15-1.82, P = .0016). Mismatch at HLA-C position 99 was associated with increased transplant-related mortality (HR = 1.37, 95% CI = 1.1-1.69, P = .0038). Mismatch at HLA-B position 9 was associated with increased chronic GVHD (HR = 2.28, 95% CI = 1.36-3.82, P = .0018). No AAS were significantly associated with outcome at HLA-A. Specific AAS pair combinations with a frequency >30 were tested for association with HCT outcomes. Cysteine to tyrosine substitution at position 99 of HLA-C was associated with increased TRM (HR = 1.78, 95% = CI 1.27-2.51, P = .0009). These results demonstrate that donor-recipient mismatch for certain peptide-binding residues of the HLA class I molecule is associated with increased risk for acute and chronic GVHD and death. PMID:23982174

  16. High resolution human leukocyte antigen (HLA) class I and class II allele typing in Mexican mestizo women with sporadic breast cancer: case-control study.

    Science.gov (United States)

    Cantú de León, David; Pérez-Montiel, Delia; Villavicencio, Verónica; García Carranca, Alejandro; Mohar Betancourt, Alejandro; Acuña-Alonzo, Victor; López-Tello, Alberto; Vargas-Alarcón, Gilberto; Barquera, Rodrigo; Yu, Neng; Yunis, Edmond J; Granados, Julio

    2009-02-05

    The development of breast cancer is multifactorial. Hormonal, environmental factors and genetic predisposition, among others, could interact in the presentation of breast carcinoma. Human leukocyte antigen (HLA) alleles play an important role in immunity (cellular immunity) and may be important genetic traits. HLAAllele-specific interaction has not been well established. Recently, several studies had been conducted in order to do so, but the results are controversial and in some instances contradictory. We designed a case-control study to quantify the association of HLA class I and II genes and breast cancer. HLA typing was performed by high resolution sequence-specific oligotyping after DNA amplification (PCR-SSOP) of 100 breast cancer Mexican mestizo patients and 99 matched healthy controls. HLA-A frequencies that we were able to observe that there was no difference between both groups from the statistical viewpoint. HLA-B*1501 was found three times more common in the case group (OR, 3.714; p = 0.031). HLA-Cw is not a marker neither for risk, nor protection for the disease, because we did not find significant statistical differences between the two groups. DRB1*1301, which is expressed in seven cases and in only one control, observing an risk increase of up to seven times and DRB1*1602, which behaves similarly in being present solely in the cases (OR, 16.701; 95% CI, 0.947 - 294.670). DQ*0301-allele expression, which is much more common in the control group and could be protective for the presentation of the disease (OR, 0.078; 95% CI, 0.027-0.223, p = 0.00001). Our results reveal the role of the MHC genes in the pathophysiology of breast cancer, suggesting that in the development of breast cancer exists a disorder of immune regulation. The triggering factor seems to be restricted to certain ethnic groups and certain geographical regions since the relevant MHC alleles are highly diverse. This is the first study in Mexican population where high resolutions HLA

  17. HLA class II (DR0401) molecules induce Foxp3+ regulatory T cell suppression of B cells in Plasmodium yoelii strain 17XNL malaria.

    Science.gov (United States)

    Wijayalath, Wathsala; Danner, Rebecca; Kleschenko, Yuliya; Majji, Sai; Villasante, Eileen Franke; Richie, Thomas L; Brumeanu, Teodor-Doru; David, Chella S; Casares, Sofia

    2014-01-01

    Unlike human malaria parasites that induce persistent infection, some rodent malaria parasites, like Plasmodium yoelii strain 17XNL (Py17XNL), induce a transient (self-curing) malaria infection. Cooperation between CD4 T cells and B cells to produce antibodies is thought to be critical for clearance of Py17XNL parasites from the blood, with major histocompatibility complex (MHC) class II molecules being required for activation of CD4 T cells. In order to better understand the correspondence between murine malaria models and human malaria, and in particular the role of MHC (HLA) class II molecules, we studied the ability of humanized mice expressing human HLA class II molecules to clear Py17XNL infection. We showed that humanized mice expressing HLA-DR4 (DR0401) molecules and lacking mouse MHC class II molecules (EA(0)) have impaired production of specific antibodies to Py17XNL and cannot cure the infection. In contrast, mice expressing HLA-DR4 (DR0402), HLA-DQ6 (DQ0601), HLA-DQ8 (DQ0302), or HLA-DR3 (DR0301) molecules in an EA(0) background were able to elicit specific antibodies and self-cure the infection. In a series of experiments, we determined that the inability of humanized DR0401.EA(0) mice to elicit specific antibodies was due to expansion and activation of regulatory CD4(+) Foxp3(+) T cells (Tregs) that suppressed B cells to secrete antibodies through cell-cell interactions. Treg depletion allowed the DR0401.EA(0) mice to elicit specific antibodies and self-cure the infection. Our results demonstrated a differential role of MHC (HLA) class II molecules in supporting antibody responses to Py17XNL malaria and revealed a new mechanism by which malaria parasites stimulate B cell-suppressogenic Tregs that prevent clearance of infection.

  18. Association between HLA class I and class II alleles and the outcome of West Nile virus infection: an exploratory study.

    Directory of Open Access Journals (Sweden)

    Marion C Lanteri

    Full Text Available BACKGROUND: West Nile virus (WNV infection is asymptomatic in most individuals, with a minority developing symptoms ranging from WNV fever to serious neuroinvasive disease. This study investigated the impact of host HLA on the outcome of WNV disease. METHODS: A cohort of 210 non-Hispanic mostly white WNV(+ subjects from Canada and the U.S. were typed for HLA-A, B, C, DP, DQ, and DR. The study subjects were divided into three WNV infection outcome groups: asymptomatic (AS, symptomatic (S, and neuroinvasive disease (ND. Allele frequency distribution was compared pair-wise between the AS, S, and ND groups using χ2 and Fisher's exact tests and P values were corrected for multiple comparisons (Pc. Allele frequencies were compared between the groups and the North American population (NA used as a control group. Logistic regression analysis was used to evaluate the potential synergistic effect of age and HLA allele phenotype on disease outcome. RESULTS: The alleles HLA-A*68, C*08 and DQB*05 were more frequently associated with severe outcomes (ND vs. AS, P(A*68 = 0.013/Pc = 0.26, P(C*08 = 0.0075/Pc = 0.064, and P(DQB1*05 = 0.029/Pc = 0.68, However the apparent DQB1*05 association was driven by age. The alleles HLA-B*40 and C*03 were more frequently associated with asymptomatic outcome (AS vs. S, P(B*40 = 0.021/Pc = 0.58 and AS vs. ND P(C*03 = 0.039/Pc = 0.64 and their frequencies were lower within WNV(+ subjects with neuroinvasive disease than within the North American population (NA vs. S, P(B*40 = 0.029 and NA vs. ND, P(C*03 = 0.032. CONCLUSIONS: Host HLA may be associated with the outcome of WNV disease; HLA-A*68 and C*08 might function as "susceptible" alleles, whereas HLA-B*40 and C*03 might function as "protective" alleles.

  19. Classification and characterization of class III malocclusion in Chinese individuals.

    Science.gov (United States)

    Li, Cai; Cai, Ying; Chen, Sihui; Chen, Fengshan

    2016-11-07

    Class III malocclusion is a maxillofacial disorder that is characterised by a concave profile and can be attributed to both genetic inheritance and environmental factors. It is a clinical challenge due to our limited understanding of its aetiology. Revealing its prototypical diversity will contribute to our sequential exploration of the underlying aetiological information. The objective of this study was to characterize phenotypic variations of Class III malocclusion via a lateral cephalometric analysis in a community of Chinese individuals. One-hundred-and-forty-four individuals (58 males ≥18 and 86 females ≥16) with Class III malocclusion ranging from mild to severe were enrolled in this study. Principal component analysis and cluster analysis were performed using 61 lateral cephalometric measurements. Six principal components were discovered in the examined population and were responsible for 73.7 % of the variability. Four subtypes were revealed by cluster analysis. Subtype 1 included subjects with mild mandibular prognathism with a steep mandibular plane. Subjects in subtype 2 showed a combination of prognathic mandibular and retrusive maxillary with a flat or normal mandibular plane. Subtype 3 included individuals with purely severe mandibular prognathism and a normal mandibular plane. Individuals in subtype 4 had a mild maxillary deficiency and severe mandibular prognathism with the lowest mandibular plane angle. The six principal components extracted among the 61 variables improve our knowledge of lateral cephalometric analysis for diagnoses. We successfully identified four Class III malocclusion subtypes, indicating that cluster analysis could supplement the classification of Class III malocclusion among a Chinese population and may assist in our on-going genetic study.

  20. Quantificação de antígenos HLA classe I solúveis pela técnica de ELISA - DOI: 10.4025/actascihealthsci.v31i2.6758 Quantification of soluble HLA class I antigens by ELISA assay- DOI: 10.4025/actascihealthsci.v31i2.6758

    Directory of Open Access Journals (Sweden)

    Marciele Coan Boian

    2009-09-01

    Full Text Available As moléculas HLA (Human Leucocyte Antigens são consideradas, principalmente, estruturas de superfície celular envolvidas em uma variedade de reações imunes associadas com transplante, infecções e doenças autoimunes. Os antígenos HLA também podem ser encontrados, em forma solúvel, no soro e em diferentes fluidos do organismo humano. Este trabalho teve como objetivo desenvolver a técnica imunoenzimática (ELISA para quantificar os níveis séricos de antígenos HLA classe I, específicos e totais, em indivíduos normais e em pacientes renais. A técnica de ELISA foi desenvolvida para demonstrar a presença, no soro, de antígenos HLA classe I totais (sHLA-I e as especificidades HLA-A2 (sHLA-A2 e HLA-B7 (sHLA-B7. Oitenta e oito amostras de soro foram envolvidas neste estudo, sendo 61 amostras provenientes de indivíduos sadios cadastrados no Hemocentro Regional de Maringá, Estado do Paraná, e 27 pacientes renais, provenientes dos centros de diálise da cidade de Maringá, Estado do Paraná. As concentrações médias de sHLA para as especificidades -A2 e -B7, detectadas somente em indivíduos sadios, foram 504.06 ng mL-1 ± 142.10 e 427.33 ng mL-1 ± 140.73, respectivamente. Resultados preliminares mostraram que sHLA-I, em indivíduos sadios, foi de 253,77 ng mL-1 e, em indivíduos renais em diálise, de 381,67 ng mL-1. A técnica de ELISA para detecção de antígenos HLA solúveis poderá ser útil em estudos comparativos, em diferentes populações saudáveis, diferentes patologias e no monitoramento das rejeições em transplantes.HLA (Human Leucocyte Antigens molecules are regarded mainly as cell surface structures involved in several immune reactions associated with transplants, infections and auto-immune diseases. HLA antigens can be also found in soluble form in serum and in different fluids of the human body. The aim of this work was to develop the immunoenzymatic assay (ELISA to quantify serum levels of specific and total

  1. Difference in treatment outcome of British and Japanese surgical class III patients associated with mandibular setback

    OpenAIRE

    Nakamura, Koyo; Nagata, Norio; IIDA, YOSHIRO; Iida, Kayo; KAGEYAMA, TORU; Ishii, Nobuyuki

    2003-01-01

    The purpose of this clinical research was to examine the racial differences in skeletal morphology of skeletal Class III abnormalities and in the ortho-surgical treatment outcome of Class III malocclusion associated with mandibular setback sagittal osteotomy between Japanese and British Caucasian female adult Class III patients. The sample consisted of 35 Class III Japanese female surgical subjects in MDU Hospital and 30 Class III British subjects (23 female and 7 male). The operative procedu...

  2. Conformational lability in the class II MHC 310 helix and adjacent extended strand dictate HLA-DM susceptibility and peptide exchange.

    Science.gov (United States)

    Painter, Corrie A; Negroni, Maria P; Kellersberger, Katherine A; Zavala-Ruiz, Zarixia; Evans, James E; Stern, Lawrence J

    2011-11-29

    HLA-DM is required for efficient peptide exchange on class II MHC molecules, but its mechanism of action is controversial. We trapped an intermediate state of class II MHC HLA-DR1 by substitution of αF54, resulting in a protein with increased HLA-DM binding affinity, weakened MHC-peptide hydrogen bonding as measured by hydrogen-deuterium exchange mass spectrometry, and increased susceptibility to DM-mediated peptide exchange. Structural analysis revealed a set of concerted conformational alterations at the N-terminal end of the peptide-binding site. These results suggest that interaction with HLA-DM is driven by a conformational change of the MHC II protein in the region of the α-subunit 3(10) helix and adjacent extended strand region, and provide a model for the mechanism of DM-mediated peptide exchange.

  3. 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

    Healthy females, pregnant with a boy, generate immune responses against male-specific minor histocompatibility (HY) antigens. The clinical importance of these responses is evident in stem cell transplantation. Birth of a boy prior to a series of miscarriages reduces the chance of a subsequent live...... 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...... 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...

  4. Conformational lability in the class II MHC 310 helix and adjacent extended strand dictate HLA-DM susceptibility and peptide exchange

    Science.gov (United States)

    Painter, Corrie A.; Negroni, Maria P.; Kellersberger, Katherine A.; Zavala-Ruiz, Zarixia; Evans, James E.; Stern, Lawrence J.

    2011-01-01

    HLA-DM is required for efficient peptide exchange on class II MHC molecules, but its mechanism of action is controversial. We trapped an intermediate state of class II MHC HLA-DR1 by substitution of αF54, resulting in a protein with increased HLA-DM binding affinity, weakened MHC-peptide hydrogen bonding as measured by hydrogen-deuterium exchange mass spectrometry, and increased susceptibility to DM-mediated peptide exchange. Structural analysis revealed a set of concerted conformational alterations at the N-terminal end of the peptide-binding site. These results suggest that interaction with HLA-DM is driven by a conformational change of the MHC II protein in the region of the α-subunit 310 helix and adjacent extended strand region, and provide a model for the mechanism of DM-mediated peptide exchange. PMID:22084083

  5. Genome-wide association study identifies new HLA class II haplotypes strongly protective against narcolepsy

    DEFF Research Database (Denmark)

    Hor, Hyun; Kutalik, Zoltán; Dauvilliers, Yves

    2010-01-01

    Narcolepsy is a rare sleep disorder with the strongest human leukocyte antigen (HLA) association ever reported. Since the associated HLA-DRB1*1501-DQB1*0602 haplotype is common in the general population (15-25%), it has been suggested that it is almost necessary but not sufficient for developing...... narcolepsy. To further define the genetic basis of narcolepsy risk, we performed a genome-wide association study (GWAS) in 562 European individuals with narcolepsy (cases) and 702 ethnically matched controls, with independent replication in 370 cases and 495 controls, all heterozygous for DRB1*1501-DQB1...... ratio = 0.02; P narcolepsy susceptibility....

  6. Diversity of natural self-derived ligands presented by different HLA class I molecules in transporter antigen processing-deficient cells.

    Directory of Open Access Journals (Sweden)

    Elena Lorente

    Full Text Available The transporter associated with antigen processing (TAP translocates the cytosol-derived proteolytic peptides to the endoplasmic reticulum lumen where they complex with nascent human leukocyte antigen (HLA class I molecules. Non-functional TAP complexes and viral or tumoral blocking of these transporters leads to reduced HLA class I surface expression and a drastic change in the available peptide repertoire. Using mass spectrometry to analyze complex human leukocyte antigen HLA-bound peptide pools isolated from large numbers of TAP-deficient cells, we identified 334 TAP-independent ligands naturally presented by four different HLA-A, -B, and -C class I molecules with very different TAP dependency from the same cell line. The repertoire of TAP-independent peptides examined favored increased peptide lengths and a lack of strict binding motifs for all four HLA class I molecules studied. The TAP-independent peptidome arose from 182 parental proteins, the majority of which yielded one HLA ligand. In contrast, TAP-independent antigen processing of very few cellular proteins generated multiple HLA ligands. Comparison between TAP-independent peptidome and proteome of several subcellular locations suggests that the secretory vesicle-like organelles could be a relevant source of parental proteins for TAP-independent HLA ligands. Finally, a predominant endoproteolytic peptidase specificity for Arg/Lys or Leu/Phe residues in the P(1 position of the scissile bond was found for the TAP-independent ligands. These data draw a new and intricate picture of TAP-independent pathways.

  7. HLA Class II Alleles Susceptibility Markers of Type 1 Diabetes Fail to Specify Phenotypes of Ketosis-Prone Diabetes in Adult Tunisian Patients

    Directory of Open Access Journals (Sweden)

    Lilia Laadhar

    2011-01-01

    Full Text Available We aimed to characterize the different subgroups of ketosis-prone diabetes (KPD in a sample of Tunisian patients using the Aβ scheme based on the presence or absence of β-cell autoantibodies (A+ or A− and β-cell functional reserve (β+ or β− and we investigated whether HLA class II alleles could contribute to distinct KPD phenotypes. We enrolled 43 adult patients with a first episode of ketosis. For all patients we evaluated clinical parameters, β-cell autoimmunity, β-cell function and HLA class II alleles. Frequency distribution of the 4 subgroups was 23.3% A+β−, 23.3% A−β−, 11.6% A+β+ and 41.9% A−β+. Patients from the group A+β− were significantly younger than those from the group A−β− (P=.002. HLA susceptibility markers were significantly more frequent in patients with autoantibodies (P=.003. These patients also had resistance alleles but they were more frequent in A+β+ than A+β− patients (P=.04. Insulin requirement was not associated to the presence or the absence of HLA susceptibility markers. HLA class II alleles associated with susceptibility to autoimmune diabetes have not allowed us to further define Tunisian KPD groups. However, high prevalence of HLA resistance alleles in our patients may reflect a particular genetic background of Tunisian KPD population.

  8. 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...

  9. Inheritance mode of multiple sclerosis : the effect of HLA class II alleles is stronger than additive

    NARCIS (Netherlands)

    Nolte, IM; De Keyser, J; Buys, CHCM; Meerman, GJT

    We previously identified on chromosome 6 an interval of 51 kb as the most likely interval in the HLA region for a disease-susceptibility locus for multiple sclerosis (MS). The interval was located between markers G511525 and D6S1666 and identified by the haplotype sharing statistic (HSS). The study

  10. HLA Class II Defects in Burkitt Lymphoma: Bryostatin-1-Induced 17 kDa Protein Restores CD4+ T-Cell Recognition

    Directory of Open Access Journals (Sweden)

    Azim Hossain

    2011-01-01

    Full Text Available While the defects in HLA class I-mediated Ag presentation by Burkitt lymphoma (BL have been well documented, CD4+ T-cells are also poorly stimulated by HLA class II Ag presentation, and the reasons underlying this defect(s have not yet been fully resolved. Here, we show that BL cells are deficient in their ability to optimally stimulate CD4+ T cells via the HLA class II pathway. The observed defect was not associated with low levels of BL-expressed costimulatory molecules, as addition of external co-stimulation failed to result in BL-mediated CD4+ T-cell activation. We further demonstrate that BL cells express the components of the class II pathway, and the defect was not caused by faulty Ag/class II interaction, because antigenic peptides bound with measurable affinity to BL-associated class II molecules. Treatment of BL with broystatin-1, a potent modulator of protein kinase C, led to significant improvement of functional class II Ag presentation in BL. The restoration of immune recognition appeared to be linked with an increased expression of a 17 kDa peptidylprolyl-like protein. These results demonstrate the presence of a specific defect in HLA class II-mediated Ag presentation in BL and reveal that treatment with bryostatin-1 could lead to enhanced immunogenicity.

  11. Class III treatment using facial mask: Stability after 10 years

    Directory of Open Access Journals (Sweden)

    Adilson Luiz Ramos

    2014-10-01

    Full Text Available Early Class III malocclusion treatment may not have long-term stability due to mandibular growth. Although some features of this malocclusion point to a better prognosis, it is practically impossible for the orthodontist to foresee cases that require new intervention. Many patients need retreatment, whether compensatory or orthodontic-surgical. The present study reports the case of a Class III patient treated at the end of the mixed dentition with the use of a face mask followed by conventional fixed appliances. The case remains stable 10 years after treatment completion. It was presented to the Brazilian Board of Orthodontics and Dentofacial Orthopedics (BBO as a requirement for the title of certified by the BBO.

  12. Orthodontics-surgical combination therapy for Class III skeletal malocclusion

    Directory of Open Access Journals (Sweden)

    M S Ravi

    2012-01-01

    Full Text Available The correction of skeletal Class III malocclusion with severe mandibular prognathism in an adult individual requires surgical and Othodontic combination therapy. The inter disciplinary approach is the treatment of choice in most of the skeletal malocclusions. A case report of an adult individual with Class III malocclusion, having mandibular excess in sagittal and vertical plane and treated with orthodontics,, bilateral sagittal split osteotomy and Le - Forte I osteotomy for the correction of skeletal, dental and soft tissue discrepancies is herewith presented. The surgical-orthodontic combination therapy has resulted in near-normal skeletal, dental and soft tissue relationship, with marked improvement in the facial esthetics in turn, has helped the patient to improve the self-confidence level.

  13. The potential of HLA-G-bearing extracellular vesicles as a future element in HLA-G immune biology

    Directory of Open Access Journals (Sweden)

    Vera eRebmann

    2016-05-01

    Full Text Available The HLA-G molecule is a member of the non-classical HLA class I family. Its surface expression is physiologically restricted to the maternal-fetal interface and to immune privileged adult tissues. Despite the restricted tissue expression, HLA-G is detectable in body fluids as secreted soluble molecules. A unique feature of HLA-G is the structural diversity as surface-expressed and as secreted molecules. Secreted HLA-G can be found in various body fluids either as free soluble HLA-G or as part of extracellular vesicles (EVs, which are composed of various antigens/ligands/receptors, bioactive lipids, cytokines, growth factors and genetic information such as mRNA and microRNA. Functionally, HLA-G and its secreted forms are considered to play a crucial role in the network of immune-regulatory tolerance mechanisms, preferentially interacting with the cognate inhibitory receptors LILRB1 and LILRB2. The HLA-G mediated tolerance is described in processes of pregnancy, inflammation, and cancer. However, almost all functional and clinical implications of HLA-G in vivo and in vitro have been established based on simple single ligand/receptor interactions at the cell surface, whereas HLA-G-bearing EVs were in minor research focus. Indeed, cytotrophoblast cells, mesenchymal stem cells and cancer cells were recently described to secrete HLA-G-bearing EVs, displaying immunosuppressive effects and modulating the tumor microenvironment. However, numerous functional and clinical open questions persist. Here, we (i introduce basic aspects of EVs biology, (ii summarize the functional knowledge, clinical implications and open questions of HLA-G-bearing EVs and (iii discuss HLA-G-bearing EVs as a future element in HLA-G biology.

  14. Surgical-orthodontic correction of a Class III dentofacial deformity

    Directory of Open Access Journals (Sweden)

    Raghu Devanna

    2010-01-01

    Full Text Available This case report describes the surgical-orthodontic treatment of a 26-year-old post-pubertal male patient with a Class III dentofacial deformity. In the pre-surgical orthodontic phase of treatment, a reverse overjet of 5.5 mm was created and arch compatibility was obtained. A mandibualr set back with BSSO was performed during surgery to restore ideal overjet, overbite, occlusion and optimal esthetics. After 1 year of treatment, the results remained stable.

  15. 培養絨毛癌細胞におけるHLA-class Iおよびclass II抗原の発現に関する研究

    OpenAIRE

    山下, 幸紀; 中村, 隆文; 清水, 哲也; 池田, 久実; 片桐, 一; Kohki, YAMASHITA; Takafumi, NAKAMURA; Tetsuya, SHIMIZU; Hisami, Ikeda; Makoto, KATAGIRI; 旭川医科大学産婦人科学講座; 旭川医科大学第2病理学講座; Department of Obstetrics and Gynecology, Asahikawa Medical Schol, Asahikawa; Department of Pathology II, Asahikawa Medical School, Asahikawa

    1986-01-01

    絨毛癌細砲における主要組織適合性抗原(Major Histocompatibility Complex:MHC antigen)の発現について再検討した.著者らが入手可能であつた8種類の絨毛癌細胞株(非妊娠性絨毛癌由来:SCH,IMa,妊娠性絨毛癌由来:BeWo,JEG-3,JaR,GCH-1,HCCM-5,NUC-1)のHLA-class IおよびHLA-class II抗原について,家兎抗HLA ABC血清および単クローン抗体W6/32(抗HLA-A,B,C),7B6(抗HLA-classII),D1-4-10(抗HLA-DR)を用いて,螢光抗体法およびRadioimmunoassay(RIA)のinhibition testにより検討した.その結果,HLA-class II抗原はいずれの細胞株においても検出されなかつた.class I抗原は,非妊娠性絨毛癌由来の株のうち,SCH(胃原発)でかなりの程度発現されていたのに対し,IMa(卵巣原発)では検出されなかつた.一方,妊娠性絨毛癌由来の株では,JaR以外のすべての細胞株には,HLA-class I抗原が微量ながら発現されて...

  16. New recombinant HLA-B alleles in a tribe of South American Amerindians indicate rapid evolution of MHC class I loci.

    Science.gov (United States)

    Watkins, D I; McAdam, S N; Liu, X; Strang, C R; Milford, E L; Levine, C G; Garber, T L; Dogon, A L; Lord, C I; Ghim, S H

    1992-05-28

    Evidence suggests that the New World was colonized only 11,000-40,000 years ago by Palaeo-Indians. The descendants of these Palaeo-Indians therefore provide a unique opportunity to study the effects of selection on major histocompatibility complex class I genes over a short period. Here we analyse the class I alleles of the Waorani of South America and the Zuni of North America. Four of the Waorani HLA-B alleles were new functional variants which could be accounted for by intralocus recombination. In contrast, all of the Zuni HLA-A and -B molecules were present in caucasians and orientals. This suggests that the new Waorani HLA-B variants arose in South America. The description of four new HLA-B alleles in the Waorani and another five new HLA-B alleles from two other tribes of South American Amerindians indicates that the HLA-B locus can evolve rapidly in isolated populations. These studies underline the importance of gathering genetic data on endangered native human populations.

  17. Association of HLA class I and II genes with cutaneous leishmaniasis: a case control study from Sri Lanka and a systematic review.

    Science.gov (United States)

    Samaranayake, Nilakshi; Fernando, Sumadhya D; Neththikumara, Nilaksha F; Rodrigo, Chaturaka; Karunaweera, Nadira D; Dissanayake, Vajira H W

    2016-06-14

    The outcome of leishmaniasis is an interplay between Leishamania and the host. Identifying contributory host genetic factors is complicated by the variability in phenotype, ethnicity and parasite species. Leishmaniasis is caused exclusively by L. donovani in Sri Lanka with localized cutaneous leishmaniasis (LCL) being the predominant form. We report here an association study of human leucocyte antigen (HLA) class I and II genes with LCL in Sri Lanka, the first on HLA associations in cutaneous leishmaniasis in a South Asian population. An existing DNA repository of 200 each of patients and controls was typed for HLA-DQ by PCR-SSP. Next generation sequencing-based typing for HLA-A, HLA-B and HLA-DRB1 alleles was done in a subset of 280 samples. Association tests were performed on 28,489 genotyped and imputed SNPs spanning a region of 1.4 Mb across the HLA genes. To compare our results with similar studies, we carried out a systematic review to document all HLA associations reported to-date for cutaneous and muco-cutaneous leishmaniasis. DRB1*04 DQB1*02 (P = 0.03; Pc = 0.09), DRB1*07 DQB1*02 (P = 0.03; Pc = 0.09) haplotypes were absent in patients. B*07 (P = 0.007; Pc = 0.13; OR = 0.36; 95 % CI = 0.17-0.77) allele and DRB1*15 DQB1*06 (P = 0.00; Pc HLA-B, comprised a haplotype more frequent in controls (P = 0.04). The alleles identified by the systematic review to predispose or to protect from cutaneous/mucocutaneous leishmaniasis remained highly heterogeneous in different populations studied. Our preliminary findings suggest a role for some class I and class II HLA genes in determining predisposition to LCL in this population which should be corroborated with further studies. The systematic review reiterates this need, as the purported susceptibility or protection gained by certain HLA alleles or haplotypes has rarely been independently verified.

  18. The Thermodynamic Mechanism of Peptide–MHC Class II Complex Formation Is a Determinant of Susceptibility to HLA-DM

    Science.gov (United States)

    Templeton, Megan; Hoffman, Megan; Castellini, Margaret J.

    2015-01-01

    Peptides bind MHC class II molecules through a thermodynamically nonadditive process consequent to the flexibility of the reactants. Currently, how the specific outcome of this binding process affects the ensuing epitope selection needs resolution. Calorimetric assessment of binding thermodynamics for hemagglutinin 306–319 peptide variants to the human MHC class II HLA-DR1 (DR1) and a mutant DR1 reveals that peptide/DR1 complexes can be formed with different enthalpic and entropic contributions. Complexes formed with a smaller entropic penalty feature circular dichroism spectra consistent with a non–compact form, and molecular dynamics simulation shows a more flexible structure. The opposite binding mode, compact and less flexible, is associated with greater entropic penalty. These structural variations are associated with rearrangements of residues known to be involved in HLA-DR (DM) binding, affinity of DM for the complex, and complex susceptibility to DM-mediated peptide exchange. Thus, the thermodynamic mechanism of peptide binding to DR1 correlates with the structural rigidity of the complex, and DM mediates peptide exchange by “sensing” flexible complexes in which the aforementioned residues are rearranged at a higher frequency than in more rigid ones. PMID:26116504

  19. The Thermodynamic Mechanism of Peptide-MHC Class II Complex Formation Is a Determinant of Susceptibility to HLA-DM.

    Science.gov (United States)

    Ferrante, Andrea; Templeton, Megan; Hoffman, Megan; Castellini, Margaret J

    2015-08-01

    Peptides bind MHC class II molecules through a thermodynamically nonadditive process consequent to the flexibility of the reactants. Currently, how the specific outcome of this binding process affects the ensuing epitope selection needs resolution. Calorimetric assessment of binding thermodynamics for hemagglutinin 306-319 peptide variants to the human MHC class II HLA-DR1 (DR1) and a mutant DR1 reveals that peptide/DR1 complexes can be formed with different enthalpic and entropic contributions. Complexes formed with a smaller entropic penalty feature circular dichroism spectra consistent with a non-compact form, and molecular dynamics simulation shows a more flexible structure. The opposite binding mode, compact and less flexible, is associated with greater entropic penalty. These structural variations are associated with rearrangements of residues known to be involved in HLA-DR (DM) binding, affinity of DM for the complex, and complex susceptibility to DM-mediated peptide exchange. Thus, the thermodynamic mechanism of peptide binding to DR1 correlates with the structural rigidity of the complex, and DM mediates peptide exchange by "sensing" flexible complexes in which the aforementioned residues are rearranged at a higher frequency than in more rigid ones. Copyright © 2015 by The American Association of Immunologists, Inc.

  20. A benefit-risk assessment of class III antiarrhythmic agents

    DEFF Research Database (Denmark)

    Brendorp, Bente; Pedersen, Oledyg; Torp-Pedersen, Christian

    2002-01-01

    With beta-blockers as the exception, increasing doubt is emerging on the value of antiarrhythmic drug therapy following a series of trials that have either shown no mortality benefit or even an excess mortality. Vaughan Williams class I drugs are generally avoided in patients with structural heart...... prevention of ventricular arrhythmias and in treatment of atrial fibrillation or flutter. Based on existing evidence there is no routine indication for antiarrhythmic drug therapy other than beta-blockers in patients at high risk of sudden death. Subgroup analyses of trials with amiodarone and dofetilide......-intervals or - in the future - from genetic testing. Class III drugs are effective in converting atrial fibrillation to sinus rhythm and for the maintenance of sinus rhythm after conversion. This is currently by far the most important indication for this class of drugs. As defined by recent guidelines, amiodarone...

  1. HLA class II alleles influence rheumatoid arthritis susceptibility and autoantibody status in South Indian Tamil population.

    Science.gov (United States)

    Mariaselvam, C M; Fortier, C; Charron, D; Krishnamoorthy, R; Tamouza, R; Negi, V S

    2016-11-01

    Rheumatoid arthritis (RA) is a complex multifactorial autoimmune disease characterized by inflammatory arthritis. The precise etiology and pathogenesis of RA remains elusive but evidence points towards stochastic interactions between genetic and environmental factors. This study investigated the distribution of human leucocyte antigen (HLA)-DRB1/DQB1 alleles in South Indian patients with rheumatoid arthritis (RA) and their influence on RA susceptibility and clinical phenotype. Low resolution HLA-DRB1 and -DQB1 typing was performed in 271 RA patients and 233 healthy controls by polymerase chain reaction (PCR) using sequence-specific primers (SSP). HLA-DRB1*10 was found to be more frequent in patients (Pc = 0.004, OR = 2.23, 95% CI = 1.5-3.34) than controls. This difference persisted in RF positive (Pc = 9 × 10(-6) , OR = 2.45, 95% CI = 1.62-3.74), ACPA positive (Pc = 0.007, OR = 2.10, 95% CI = 1.35-3.29), ACPA negative (Pc = 0.001, OR = 2.45, 95% CI = 1.50-3.97) and both RF and ACPA positive subgroup of patients (Pc = 0.003, OR = 2.22, 95% CI = 1.41-3.51). On the contrary, the HLA-DRB1*13 (Pc = 0.01, OR = 0.43, 95% CI = 0.25-0.73) and HLA-DRB1*14 (Pc = 0.003, OR = 0.43, 95% CI = 0.26-0.69) alleles were over-represented in controls than patients. Further, distribution of the prominent Caucasian RA risk allele DRB1*04 did not differ between patients and controls in our study population. We did not find any association between DQB1 alleles and RA susceptibility or autoantibody status. The haplotypes DQB1*05-DRB1*10 (P = 6.8 × 10(-6) , OR = 2.46, 95% CI = 1.63-3.79) and DQB1*06-DRB1*15 (P = 0.03, OR = 1.41, 95% CI = 1.02-1.96) were more frequent in patients while DQB1*05-DRB1*14 (P = 8.4 × 10(-4) , OR = 0.44, 95% CI = 0.26-0.74) and DQB1*06-DRB1*13 (P = 9.5 × 10(-4) , OR = 0.40, 95% CI = 0.21-0.72) were higher in controls. To conclude, HLA-DRB1*10 is associated with RA while HLA-DRB1*13 and HLA-DRB1*14 alleles confer protection in south Indian Tamils. © 2016 John

  2. Alloactivated HLA class II-positive T-cell lines induce IL-2 reactivity but lack accessory cell function in mixed leukocyte culture

    DEFF Research Database (Denmark)

    Odum, N; Dickmeiss, E; Hofmann, B

    1989-01-01

    Recently, much interest has focused on the role of HLA class II antigens in T cell-T cell interactions. We have studied the stimulatory capability in the primary mixed leukocyte reaction and the primed lymphocyte reaction of 11 alloactivated, HLA-DR- or -DP-reactive CD4-positive T-cell lines (Ta)...... cells. Thus, allogeneic class II-positive Ta can induce interleukin 2 responsiveness but lack accessory cell function(s) necessary for the induction of interleukin 2 production in primed and unprimed T cells....

  3. Compensatory canine angulation in angle Class II and III patients

    Directory of Open Access Journals (Sweden)

    Mauro Carlos Agner Busato

    2009-09-01

    Full Text Available The aim of this study was to evaluate the occurence of compensation in mesiodistal axial inclinations of canines in skeletal malocclusions patients. The sample consisted of 25 Angle Class II, division 1 malocclusion (group 1 and 19 Angle Class III malocclusion patients (group 2. After measurement of dental angulations through a method that associates plaster model photography and AutoCad software, comparisons between the groups were performed by T-test for independent samples. Results showed that there was no statistically significant difference (p < 0.05 between groups, when maxillary canine angulations were compared. Regarding the mandibular canines, there was a statistically significant difference in dental angulation, expressed by 3.2° for group 1 and 0.15° for group 2. An upright position tendency for mandibular canines was observed in the Angle Class III sample. This configures a pattern of compensatory coronary positioning, since the angulation of these teeth makes them occupy less space in the dental arch and consequently mandibular incisors can be in a more retracted position in the sagittal plane.

  4. CD94-NKG2A Recognition of Human Leukocyte Antigen (HLA)-E Bound to an HLA Class I Leader Sequence

    Energy Technology Data Exchange (ETDEWEB)

    Petrie,E.; Clements, C.; Lin, J.; Sullivan, L.; Johnson, D.; Huyton, T.; Heroux, A.; Hoare, H.; Beddoe, T.; et al

    2008-01-01

    The recognition of human leukocyte antigen (HLA)-E by the heterodimeric CD94-NKG2 natural killer (NK) receptor family is a central innate mechanism by which NK cells monitor the expression of other HLA molecules, yet the structural basis of this highly specific interaction is unclear. Here, we describe the crystal structure of CD94-NKG2A in complex with HLA-E bound to a peptide derived from the leader sequence of HLA-G. The CD94 subunit dominated the interaction with HLA-E, whereas the NKG2A subunit was more peripheral to the interface. Moreover, the invariant CD94 subunit dominated the peptide-mediated contacts, albeit with poor surface and chemical complementarity. This unusual binding mode was consistent with mutagenesis data at the CD94-NKG2A-HLA-E interface. There were few conformational changes in either CD94-NKG2A or HLA-E upon ligation, and such a 'lock and key' interaction is typical of innate receptor-ligand interactions. Nevertheless, the structure also provided insight into how this interaction can be modulated by subtle changes in the peptide ligand or by the pairing of CD94 with other members of the NKG2 family. Differences in the docking strategies used by the NKG2D and CD94-NKG2A receptors provided a basis for understanding the promiscuous nature of ligand recognition by NKG2D compared with the fidelity of the CD94-NKG2 receptors.

  5. Oropharyngeal airway in children with Class III malocclusion evaluated by cone-beam computed tomography.

    Science.gov (United States)

    Iwasaki, Tomonori; Hayasaki, Haruaki; Takemoto, Yoshihiko; Kanomi, Ryuzo; Yamasaki, Youichi

    2009-09-01

    Upper airway size is increasingly recognized as an important factor in malocclusion. However, children with Class III malocclusion are somewhat neglected compared with those with a Class II skeletal pattern. Therefore, the purpose of this study was to establish the characteristic shape of the oropharyngeal airway (OA) in children with Class III malocclusion. The sample comprised 45 children (average age, 8.6 +/- 1.0 years) divided into 2 groups: 25 with Class I and 20 with Class III malocclusions. OA size of each group was evaluated by cone-beam computed tomography. Cluster analysis, based on OA shape, redivided the subjects into wide, square, and long types. The distributions of Class I and Class III subjects were compared among the types. The Class III group showed statistically larger OA area and width compared with the Class I group. Area was positively correlated with Class III severity. The square type included 84% of the Class I malocclusions but only 30% of the Class III malocclusions, indicating that the OA in Class III malocclusion tends to be flat. The Class III malocclusion is associated with a large and flat OA compared with the Class I malocclusion.

  6. Treatment of Class III Malocclusion: Atypical Extraction Protocol

    Directory of Open Access Journals (Sweden)

    Fernando Pedrin Carvalho Ferreira

    2017-01-01

    Full Text Available The treatment of Angle Class III malocclusion is rather challenging, because the patient’s growth pattern determines the success of long-term treatment. Early diagnosis and treatment are still highly discussed issues in orthodontic literature. This type of early intervention has been indicated more frequently in order to eliminate primary etiological factors and prevent an already present malocclusion from becoming severe. However, when a patient is diagnosed in adulthood, manipulation of the bone bases becomes extremely limited, as there is no longer any potential for growth. Treatments are restricted to dental compensations when possible or orthognathic surgery. However, owing to the high cost and inherent risk of the surgical procedure, this treatment option is often denied by the patient; in such a case, the orthodontist has little choice but to perform, where possible, compensatory treatments to restore a functional occlusion and improve facial esthetics. This article reports a case of Class III malocclusion in a patient who opted for compensatory treatment with lower molar extraction that allowed for correction of the midline and the overjet. Good facial esthetics and functional normal occlusion were achieved at the end of the treatment.

  7. Vertical control in the Class III compensatory treatment

    Directory of Open Access Journals (Sweden)

    Márcio Costa Sobral

    2013-04-01

    Full Text Available INTRODUCTION: Compensatory orthodontic treatment, or simply orthodontic camouflage, consists in an important alternative to orthognathic surgery in the resolution of skeletal discrepancies in adult patients. It is important to point that, to be successfully performed, diagnosis must be detailed, to evaluate, specifically, dental and facial features, as well as the limitations imposed by the magnitude of the discrepancy. The main complaint, patient's treatment expectation, periodontal limits, facial pattern and vertical control are some of the items to be explored in the determination of the viability of a compensatory treatment. Hyperdivergent patients who carry a Class III skeletal discrepancy, associated with a vertical facial pattern, with the presence or tendency to anterior open bite, deserve special attention. In these cases, an efficient strategy of vertical control must be planned and executed. OBJECTIVE: The present article aims at illustrating the evolution of efficient alternatives of vertical control in hiperdivergent patients, from the use, in the recent past, of extra-oral appliances on the lower dental arch (J-hook, until nowadays, with the advent of skeletal anchorage. But for patients with a more balanced facial pattern, the conventional mechanics with Class III intermaxillary elastics, associated to an accentuated curve of Spee in the upper arch and a reverse Curve of Spee in the lower arch, and vertical elastics in the anterior region, continues to be an excellent alternative, if there is extreme collaboration in using the elastics.

  8. Signal transduction by HLA class II molecules in human T cells: induction of LFA-1-dependent and independent adhesion

    DEFF Research Database (Denmark)

    Odum, Niels; Yoshizumi, H; Okamoto, Y

    1992-01-01

    Crosslinking HLA-DR molecules by monoclonal antibodies (moAbs) induces protein tyrosine phosphorylation and results in a secondary elevation of free cytoplasmic calcium concentrations in activated human T cells. Binding of bacterial superantigens or moAbs to DR molecules on activated T cells...... was recently reported to induce homotypic aggregation through activation of protein kinase C (PKC) and mediated by CD11a/CD54 (LFA-1/CAM-1) adhesion molecules. Here, we report that moAbs directed against framework DR, but neither DR1, 2- and DRw52- nor DQ- and DP-specific moABs induced homotypic aggregation...... of antigen- and alloantigen-activated T cells, antigen-specific CD4+ T-cell lines, a CD8+ T-cytotoxic cell line, and T-leukemia cells (HUT78). Protein tyrosine kinase (PTK) inhibitor herbimycin A partly blocked class-II-induced aggregation responses. In contrast, phorbol ester (PMA)-induced aggregation...

  9. Somatic Variation of T-Cell Receptor Genes Strongly Associate with HLA Class Restriction.

    Directory of Open Access Journals (Sweden)

    Paul L Klarenbeek

    Full Text Available Every person carries a vast repertoire of CD4+ T-helper cells and CD8+ cytotoxic T cells for a healthy immune system. Somatic VDJ recombination at genomic loci that encode the T-cell receptor (TCR is a key step during T-cell development, but how a single T cell commits to become either CD4+ or CD8+ is poorly understood. To evaluate the influence of TCR sequence variation on CD4+/CD8+ lineage commitment, we sequenced rearranged TCRs for both α and β chains in naïve T cells isolated from healthy donors and investigated gene segment usage and recombination patterns in CD4+ and CD8+ T-cell subsets. Our data demonstrate that most V and J gene segments are strongly biased in the naïve CD4+ and CD8+ subsets with some segments increasing the odds of being CD4+ (or CD8+ up to five-fold. These V and J gene associations are highly reproducible across individuals and independent of classical HLA genotype, explaining ~11% of the observed variance in the CD4+ vs. CD8+ propensity. In addition, we identified a strong independent association of the electrostatic charge of the complementarity determining region 3 (CDR3 in both α and β chains, where a positively charged CDR3 is associated with CD4+ lineage and a negatively charged CDR3 with CD8+ lineage. Our findings suggest that somatic variation in different parts of the TCR influences T-cell lineage commitment in a predominantly additive fashion. This notion can help delineate how certain structural features of the TCR-peptide-HLA complex influence thymic selection.

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

    Science.gov (United States)

    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

  11. Early class III management in deciduous dentition using reverse twin block

    OpenAIRE

    S S Sargod; N Shetty; A Shabbir

    2013-01-01

    Class III malocclusion poses a challenging dilemma for the clinician because these children have of growth patterns that differ from that of children with class I malocclusion. The mandible grows more rapidly than the maxilla, exacerbating the class III malocclusion as the child go through adolescence. Ever since Clark described a version of the twin block, it has steadily gained popularity in the management of early class III malocclusion in children. However, not many cases are reported in ...

  12. Expression of the multiple sclerosis-associated MHC class II Allele HLA-DRB1*1501 is regulated by vitamin D.

    Directory of Open Access Journals (Sweden)

    Sreeram V Ramagopalan

    2009-02-01

    Full Text Available Multiple sclerosis (MS is a complex trait in which allelic variation in the MHC class II region exerts the single strongest effect on genetic risk. Epidemiological data in MS provide strong evidence that environmental factors act at a population level to influence the unusual geographical distribution of this disease. Growing evidence implicates sunlight or vitamin D as a key environmental factor in aetiology. We hypothesised that this environmental candidate might interact with inherited factors and sought responsive regulatory elements in the MHC class II region. Sequence analysis localised a single MHC vitamin D response element (VDRE to the promoter region of HLA-DRB1. Sequencing of this promoter in greater than 1,000 chromosomes from HLA-DRB1 homozygotes showed absolute conservation of this putative VDRE on HLA-DRB1*15 haplotypes. In contrast, there was striking variation among non-MS-associated haplotypes. Electrophoretic mobility shift assays showed specific recruitment of vitamin D receptor to the VDRE in the HLA-DRB1*15 promoter, confirmed by chromatin immunoprecipitation experiments using lymphoblastoid cells homozygous for HLA-DRB1*15. Transient transfection using a luciferase reporter assay showed a functional role for this VDRE. B cells transiently transfected with the HLA-DRB1*15 gene promoter showed increased expression on stimulation with 1,25-dihydroxyvitamin D3 (P = 0.002 that was lost both on deletion of the VDRE or with the homologous "VDRE" sequence found in non-MS-associated HLA-DRB1 haplotypes. Flow cytometric analysis showed a specific increase in the cell surface expression of HLA-DRB1 upon addition of vitamin D only in HLA-DRB1*15 bearing lymphoblastoid cells. This study further implicates vitamin D as a strong environmental candidate in MS by demonstrating direct functional interaction with the major locus determining genetic susceptibility. These findings support a connection between the main epidemiological and

  13. Early treatment of class III malocclusion with facemask.

    Science.gov (United States)

    Smyth, Robert S D; Ryan, Fiona S

    2017-12-22

    Data sourcesThe Cochrane Central Register of Controlled Trials, Cochrane Database of Systematic Reviews, Embase, Medline and the ClinicalTrials.gov databases.Study selectionRandomised controlled trials (RCTs) and controlled clinical trials (CCTs) of children aged 7-12 years with class III malocclusion undergoing fixed or removable orthodontic treatment for early correction were included.Data extraction and synthesisTwo reviewers independently selected studies, abstracted data and assessed risk of bias. The Cochrane risk of bias tool was used for RCTs and the Downs and Black and the Newcastle-Ottawa scales for CCTs. The primary outcome was correction of reverse overjet. Mean differences (MD) with 95% confidence intervals were calculated and a random effects meta-analysis conducted.ResultsFifteen studies (nine RCTs, six CCTs) were included. Only three of the RCTs were considered to be at low risk of bias, all six CCTs were at high risk of bias.Three RCTs (141 patients) compared protraction facemask and untreated control. The results for reverse overjet (MD = 2.5 mm; 95% CI, 1.21-3.79) and ANB angle (MD = 3.90˚; 95% CI, 3.54-4.25) were statistically significant favouring the facemask group. All CCTs demonstrated a statistically significant benefit in favour of the use of each appliance. However, the studies had high risk of bias.ConclusionsThere is a moderate amount of evidence to show that early treatment with a facemask results in positive improvement for both skeletal and dental effects in the short term. However, there was lack of evidence on long-term benefits. There is some evidence with regard to the chincup, tandem traction bow appliance and removable mandibular retractor, but the studies had a high risk of bias. Further high-quality, long-term studies are required to evaluate the early treatment effects for Class III malocclusion patients.

  14. HLA-G 3’UTR Polymorphisms Impact the Prognosis of Stage II-III CRC Patients in Fluoropyrimidine-Based Treatment

    Science.gov (United States)

    Garziera, Marica; Bidoli, Ettore; Cecchin, Erika; Mini, Enrico; Nobili, Stefania; Lonardi, Sara; Buonadonna, Angela; Errante, Domenico; Pella, Nicoletta; D’Andrea, Mario; De Marchi, Francesco; De Paoli, Antonino; Zanusso, Chiara; De Mattia, Elena; Tassi, Renato; Toffoli, Giuseppe

    2015-01-01

    An important hallmark of CRC is the evasion of immune surveillance. HLA-G is a negative regulator of host’s immune response. Overexpression of HLA-G protein in primary tumour CRC tissues has already been associated to worse prognosis; however a definition of the role of immunogenetic host background is still lacking. Germline polymorphisms in the 3’UTR region of HLA-G influence the magnitude of the protein by modulating HLA-G mRNA stability. Soluble HLA-G has been associated to 3’UTR +2960 Ins/Ins and +3035 C/T (lower levels) and +3187 G/G (high levels) genotypes. HLA-G 3’UTR SNPs have never been explored in CRC outcome. The purpose of this study was to investigate if common HLA-G 3’UTR polymorphisms have an impact on DFS and OS of 253 stage II-III CRC patients, after primary surgery and ADJ-CT based on FL. The 3’UTR was sequenced and SNPs were analyzed for their association with survival by Kaplan-Meier and multivariate Cox models; results underwent internal validation using a resampling method (bootstrap analysis). In a multivariate analysis, we estimated an association with improved DFS in Ins allele (Ins/Del +Ins/Ins) carriers (HR 0.60, 95% CI 0.38–0.93, P = 0.023) and in patients with +3035 C/T genotype (HR 0.51, 95% CI 0.26–0.99, P = 0.045). The +3187 G/G mutated carriers (G/G vs A/A+A/G) were associated to a worst prognosis in both DFS (HR 2.46, 95% CI 1.19–5.05, P = 0.015) and OS (HR 2.71, 95% CI 1.16–6.63, P = 0.022). Our study shows a prognostic and independent role of 3 HLA-G 3’UTR SNPs, +2960 14-bp INDEL, +3035 C>T, and +3187 A>G. PMID:26633805

  15. Relationships among nasal resistance, adenoids, tonsils, and tongue posture and maxillofacial form in Class II and Class III children.

    Science.gov (United States)

    Iwasaki, Tomonori; Sato, Hideo; Suga, Hokuto; Takemoto, Yoshihiko; Inada, Emi; Saitoh, Issei; Kakuno, Eriko; Kanomi, Ryuzo; Yamasaki, Youichi

    2017-05-01

    The purpose of this study was to clarify the relationships between upper airway factors (nasal resistance, adenoids, tonsils, and tongue posture) and maxillofacial forms in Class II and III children. Sixty-four subjects (mean age, 9.3 years) with malocclusion were divided into Class II and Class III groups by ANB angles. Nasal resistance was calculated using computational fluid dynamics from cone-beam computed tomography data. Adenoids, tonsils, and tongue posture were evaluated in the cone-beam computed tomography images. The groups were compared using Mann-Whitney U tests and Student t tests. The Spearman rank correlations test assessed the relationships between the upper airway factors and maxillofacial form. Nasal resistance of the Class II group was significantly larger than that of the Class III group (P = 0.005). Nasal resistance of the Class II group was significantly correlated with inferior tongue posture (P Class III group was significantly correlated with anterior tongue posture (P Class III group was significantly correlated with mandibular protrusion. The relationships of upper airway factors differ between Class II and Class III children. Copyright © 2017 American Association of Orthodontists. Published by Elsevier Inc. All rights reserved.

  16. Cephalometric characteristics of Korean children with Class III malocclusion in the deciduous dentition.

    Science.gov (United States)

    Choi, Hyung-Jun; Kim, Ji-Yeon; Yoo, Seung Eun; Kwon, Jang-Hyuk; Park, Kitae

    2010-01-01

    To compare the cephalometric characteristics of children with Class III malocclusion to those of children with normal occlusion during the deciduous dentition phase. Cephalometric measurements of 27 children (mean age: 5.03 years) diagnosed with Class III malocclusion were compared with 32 children (mean age: 4.85 years) diagnosed with normal occlusion in the following four categories: sagittal skeletal analysis, vertical skeletal analysis, dentoalveolar analysis, and soft tissue analysis. Significant differences were seen in all categories except vertical skeletal analysis. Sagittal skeletal measurements included ANB (Class III group: -0.91 +/- 1.60; normal group: 5.28 +/- 1.29), facial convexity (Class III group: 0.47 +/- 4.32; normal group: 13.65 +/- 3.44), Wits appraisal (Class III group: -5.54 +/- 2.36; normal group: -0.84 +/- 1.91), and A to N-perpendicular (Class III group: -2.94 +/- 3.05; normal group: 0.78 +/- 2.53). Dentoalveolar measurements included U1 to NA (Class III group: 11.98 +/- 5.25; normal group: 8.12 +/- 5.43), IMPA (Class III group: 81.34 +/- 7.40; normal group: 86.57 +/- 5.67), and interincisal angle (Class III group: 152.65 +/- 8.82; normal group: 145.03 +/- 7.34). Soft tissue measurements included soft tissue convexity (Class III group: 2.47 +/- 4.20; normal group: 12.71 +/- 3.95), nasofacial angle (Class III group: 22.68 +/- 4.22; normal group: 26.24 +/- 3.84), and upper lip to esthetic plane (Class III group: -0.65 +/- 2.74; normal group: 3.07 +/- 1.90). There are significant differences between the craniofacial patterns of normal children and those of children with Class III malocclusion that can be identified with cephalometric analysis as early as the deciduous dentition phase.

  17. Completion of HLA protein sequences by automated homology-based nearest-neighbor extrapolation of HLA database sequences

    NARCIS (Netherlands)

    Geneugelijk, K; Niemann, M; de Hoop, T; Spierings, E

    The IMGT/HLA database contains every publicly available HLA sequence. However, most of these HLA protein sequences are restricted to the alpha-1/alpha-2 domain for HLA class-I and alpha-1/beta-1 domain for HLA class-II. Nevertheless, also polymorphism outside these domains may play a role in

  18. Completion of HLA protein sequences by automated homology-based nearest-neighbor extrapolation of HLA database sequences

    NARCIS (Netherlands)

    Geneugelijk, K|info:eu-repo/dai/nl/413648699; Niemann, M; de Hoop, T; Spierings, E|info:eu-repo/dai/nl/195438728

    2016-01-01

    The IMGT/HLA database contains every publicly available HLA sequence. However, most of these HLA protein sequences are restricted to the alpha-1/alpha-2 domain for HLA class-I and alpha-1/beta-1 domain for HLA class-II. Nevertheless, also polymorphism outside these domains may play a role in

  19. Evaluation depth of the curve of Spee in class I, class II, and class III malocclusion: A cross sectional study

    Directory of Open Access Journals (Sweden)

    Sanjna Nayar

    2015-01-01

    Full Text Available Occlusal plane is an essential consideration when multiple long-span posterior restorations are designed. When restorations are added to an existing tooth arrangement characterized by rotated, tipped, or extruded teeth, excursive interferences may be incorporated, resulting in detrimental squeal. The curve of Spee, which exists in the ideal natural dentition, allows harmony to exist between the anterior tooth and condylar guidance. This curve exists in the sagittal plane and is the best viewed from a lateral aspect. It permits total posterior disclusion on mandibular protrusion, given proper anterior tooth guidance. It is unclear that whether the curve of Spee is a description of the occlusal surface of each arch separately or in maximal intercuspation. The purpose of this study was to examine the differences in the depth of curve of Spee between the class I, class II, class III and to investigate the relationship of depth of curve of Spee with over jet, over-bite.

  20. 40 CFR 147.1401 - State administered program-Class I, III, IV and V wells.

    Science.gov (United States)

    2010-07-01

    ... CONTROL PROGRAMS Nebraska § 147.1401 State administered program—Class I, III, IV and V wells. The UIC program for Class I, III, IV, and V wells in the State of Nebraska, except those on Indian lands, is the... 40 Protection of Environment 22 2010-07-01 2010-07-01 false State administered program-Class I...

  1. Influence of HLA class I haplotypes on HIV-1 seroconversion and disease progression in Pumwani sex worker cohort.

    Directory of Open Access Journals (Sweden)

    Raghavan Sampathkumar

    Full Text Available We examined the effect of HLA class I haplotypes on HIV-1 seroconversion and disease progression in the Pumwani sex worker cohort. This study included 595 HIV-1 positive patients and 176 HIV negative individuals. HLA-A, -B, and -C were typed to 4-digit resolution using sequence-based typing method. HLA class I haplotype frequencies were estimated using PyPop 32-0.6.0. The influence of haplotypes on time to seroconversion and CD4+ T cell decline to <200 cells/mm3 were analyzed by Kaplan-Meier analysis using SPSS 13.0. Before corrections for multiple comparisons, three 2-loci haplotypes were significantly associated with faster seroconversion, including A*23∶01-C*02∶02 (p = 0.014, log rank(LR = 6.06, false-discovery rate (FDR = 0.056, B*42∶01-C*17∶01 (p = 0.01, LR = 6.60, FDR = 0.08 and B*07∶02-C*07∶02 (p = 0.013, LR = 6.14, FDR = 0.069. Two A*74∶01 containing haplotypes, A*74∶01-B*15∶03 (p = 0.047, LR = 3.942, FDR = 0.068 and A*74∶01-B*15∶03-C*02∶02 (p = 0.045, LR = 4.01, FDR = 0.072 and B*14∶02-C*08∶02 (p = 0.021, LR = 5.36, FDR = 0.056 were associated with slower disease progression. Five haplotypes, including A*30∶02-B*45∶01 (p = 0.0008, LR = 11.183, FDR = 0.013, A*30∶02-C*16∶01 (p = 0.015, LR = 5.97, FDR = 0.048, B*53∶01-C*04∶01 (p = 0.010, LR = 6.61, FDR = 0.08, B*15∶10-C*03∶04 (p = 0.031, LR = 4.65, FDR = 0.062, and B*58∶01-C*03∶02 (p = 0.037, LR = 4.35, FDR = 0.066 were associated with faster progression to AIDS. After FDR corrections, only the associations of A*30∶02-B*45∶01 and A*30∶02-C*16∶01 with faster disease progression remained significant. Cox regression and deconstructed Kaplan-Meier survival analysis showed that the associations of haplotypes of A*23∶01-C*02∶02, B*07∶02-C*07∶02, A*74∶01-B*15∶03, A*74∶01-B*15∶03-C*02∶02, B*14

  2. The tetraspan protein CD82 is a resident of MHC class II compartments where it associates with HLA-DR, -DM, and -DO molecules.

    Science.gov (United States)

    Hammond, C; Denzin, L K; Pan, M; Griffith, J M; Geuze, H J; Cresswell, P

    1998-10-01

    In specialized APCs, MHC class II molecules are synthesized in the endoplasmic reticulum and transported through the Golgi apparatus to organelles of the endocytic pathway collectively called MHC class II compartments (MIICs). There, the class II-associated invariant chain is degraded, and peptides derived from internalized Ag bind to empty class II in a reaction that is facilitated by the class II-like molecule HLA-DM. An mAb raised to highly purified, immunoisolated MIICs from human B lymphoblastoid cells recognized CD82, a member of the tetraspan family of integral membrane proteins. Subcellular fractionation, immunofluorescence microscopy, and immunoelectron microscopy showed that CD82 is highly enriched in MIICs, particularly in their internal membranes. Coprecipitation analysis showed that CD82 associates in MIICs with class II, DM, and HLA-DO (an inhibitor of peptide loading that binds DM). Similar experiments showed CD63, another tetraspan protein found in MIICs, also associates with these molecules in the compartment and that CD82 and CD63 associate with each other. Preclearing experiments demonstrated that both CD82 and CD63 form complexes with DM-associated class II and DM-associated DO. The ability of CD82 and CD63 to form complexes with class II, DM, and DO in MIICs suggests that the tetraspan proteins may play an important role in the late stages of MHC class II maturation.

  3. HLA-B allele and haplotype diversity among Thai patients identified by PCR-SSOP: evidence for high risk of drug-induced hypersensitivity

    Directory of Open Access Journals (Sweden)

    CHONLAPHAT eSUKASEM

    2015-01-01

    Full Text Available BACKGROUND: There are 3 classes of HLA molecules; HLA class I, II and III, of which different classes have different functions. HLA-B gene which belongs to HLA class I play an important role predicting drug hypersensitivity. MATERIALS AND METHODS: Nine hundred and eighty-six Thai subjects who registered at a pharmacogenomics laboratory were determined for HLA-B genotype using a two-stage sequence-specific oligonucleotide probe system (PCR-SSOP. RESULTS: In this study, HLA-B alleles did not deviate from Hardy-Weinberg equilibrium (P>0.05. The most common HLA-B alleles observed in this population were HLA-B*46:01 (11.51%, HLA-B*58:01 (8.62%, HLA-B*40:01 (8.22%, HLA-B*15:02 (8.16% and HLA-B*13:01 (6.95%. This finding revealed that HLA-B allele frequency in the Thai population was consistent with the Chinese population (p>0.05, however, differed from the Malaysian population (p<0.05. The top five HLA-B genotypes were HLA-B*40:01/46:01 (2.13%, HLA-B*46:01/46:01 (2.03%, HLA-B*40:01/58:01 (2.03%, HLA-B*46:01/58:01 (1.93% and HLA-B*15:02/46:01 (1.83%. This study found that 15.92% of Thai subjects carry HLA-B*15:02, which has been associated with carbamazepine-induced severe cutaneous adverse drug reactions (SCARs. Moreover, 16.33% of Thai subjects carry the HLA-B*58:01 allele, which has been associated with allopurinol-induced SCARs. CONCLUSION: This study demonstrates a high diversity of HLA-B polymorphisms in this Thai population. The high frequency of HLA-B pharmacogenomic markers in the population emphasizes the importance of such screening to predict/avoid drug hypersensitivity.

  4. Stability of bimaxillary surgery on Class III malocclusion treatment

    Directory of Open Access Journals (Sweden)

    Fernando Antonio Gonçalves

    2012-12-01

    Full Text Available OBJECTIVE: To evaluate the stability of bimaxillary surgery in patients with skeletal malocclusion, with the use of rigid internal fixation. METHODS: Lateral cephalograms from 20 patients, 11 males and 9 females, mean age of 26 years and 1 month, were evaluated before surgery, immediately post-operative and at least 6 months after surgery. Nineteen cephalometric measurements were evaluated, and the results were statistically analyzed by means of the Student's t test and the Kruskal-Wallis test. RESULTS: The Le Fort I maxillary advancement surgery showed almost no relapse. There was lack of stability of mandibular setback, with relapse of 37.33% on point B, due to counterclockwise rotation of the mandible between post-operative periods, occurred by better intercuspation after surgery and muscle adaptation. The results showed the same tendencies for both genders. CONCLUSION: It was concluded that on the bimaxillary surgery treatment of Class III malocclusion, the maxillary surgery was very stable, but the mandibular setback recurred. No statistical differences were found in surgical stability between genders.OBJETIVO: avaliar a estabilidade da cirurgia combinada de maxila e mandíbula em pacientes com má oclusão esquelética de Classe III com a utilização de fixação interna rígida. MÉTODOS: utilizaram-se telerradiografias obtidas em norma lateral de 20 pacientes, sendo 11 do sexo masculino e 9 do feminino, com média de idade de 26 anos e 1 mês, avaliados antes da cirurgia, no pós-operatório imediato e no mínimo 6 meses após a cirurgia. Avaliaram-se dezenove grandezas cefalométricas e os resultados foram analisados estatisticamente por meio do teste t de Student e da análise de Kruskal-Wallis. RESULTADOS: a cirurgia de avanço maxilar praticamente não apresentou recidiva. Ocorreu perda de estabilidade do recuo mandibular, com recidiva de 37,33% no ponto B, devido ao giro anti-horário da mandíbula entre os períodos p

  5. Pressure from the lips and the tongue in children with class III malocclusion*

    OpenAIRE

    Ruan, Wen-hua; Su, Ji-mei; Ye, Xiao-wei

    2007-01-01

    Objective: To discuss possible relationships between class III malocclusion and perioral forces by measuring the pressure from the lips and the tongue of children with class III malocclusion. Methods: Thirty-one children with class III malocclusion were investigated and their perioral forces were measured at rest and during swallowing under natural head position by a custom-made miniperioral force computer measuring system. Results: The resting pressures exerted on the labial side and palatin...

  6. Surgical treatment of dental and skeletal Class III malocclusion

    Directory of Open Access Journals (Sweden)

    Ione Helena Vieira Portella Brunharo

    2013-02-01

    Full Text Available Orthodontic preparation for surgical treatment of skeletal Class III malocclusion involves joint planning with an oral and maxillofacial surgeon to address the functional and esthetic needs of the patient. In order to allow surgical manipulation of the jaws in the preoperative phase, the need to achieve a negative overjet through incisor decompensation often leads the orthodontist to extract the upper first premolars. This report illustrates an orthodontic preparation case where due to specific factors inherent in the patient's psychological makeup retroclination of the upper incisors and proclination of the mandibular incisors was achieved without removing any teeth. This case was presented to the Brazilian Board of Orthodontics and Facial Orthopedics (BBO in partial fulfillment of the requirements for obtaining the BBO Diploma.O preparo ortodôntico para tratamento cirúrgico do padrão esquelético de Classe III envolve o planejamento em conjunto com o cirurgião bucomaxilofacial, com o objetivo de solucionar as necessidades funcionais e estéticas do paciente. A fim de permitir a manipulação cirúrgica das bases ósseas, a obtenção de overjet negativo por meio da descompensação dos incisivos, na fase pré-cirúrgica, leva, com frequência, o ortodontista a optar pela exodontia dos primeiros pré-molares superiores. O presente relato ilustra um caso de preparo ortodôntico no qual, devido a fatores específicos inerentes à questão psicológica da paciente, a retroinclinação dos incisivos superiores e vestibularização dos incisivos inferiores foi realizada sem a remoção de elementos dentários. Esse caso foi apresentado à diretoria do Board Brasileiro de Ortodontia e Ortopedia Facial (BBO como parte dos requisitos para a obtenção do título de Diplomado pelo BBO.

  7. [Morphological characteristics of mandibular symphysis in adult skeletal class II and class III malocclusions with abnormal vertical skeletal patterns].

    Science.gov (United States)

    Tang, Na; Zhao, Zhi-he; Liao, Chun-hui; Zhao, Mei-ying

    2010-08-01

    To figure out the differences of the morphological characteristics of mandibular symphysis between Class II and Class III adult skeletal malocclusions with different abnormal vertical skeletal patterns. 109 Chinese female adults of skeletal Class II and Class III were chosen and divided into four groups according to vertical and sagittal skeletal pattern: Class II--vertical-growth-pattern group (n=30), Class III--vertical-growth-pattern group (n=25), Class II--horizontal-growth-pattern group (n=29), Class III--horizontal-growth-pattern (n=25). Lateral cephalograms were taken. The symphyseal widths and heights, along with lower incisor positions were evaluated. Observation and statistics analysis were done to clarify the morphological characteristics of the symphyseal region of different skeletal patterns. There were morphological differences of symphyseal region between Class II and Class III skeletal malocclusions, but not significant in width and total height. With a vertical-growth-pattern, Class II malocclusions had higher alveolus than Class III, but smaller chin prominence and lower basal bone (P pattern, Class II malocclusions had higher alveolus (P skeletal pattern, vertical-growth-pattern group had thinner but higher symphyseal region and bigger chin prominence (P pattern malocclusion was prone to have a cucurbit-morph chin, of which Id width was larger than basal width (P skeletal malocclusions with different abnormal vertical skeletal patterns. The influence of abnormal vertical skeletal pattern to symphyseal morphological characteristics is greater than that of abnormal sagittal skeletal pattern. There is a risk of orthodontic movement of low incisors in vertical-growth-pattern skeletal malocclusion.

  8. Early treatment of Class III malocclusion by RME and modified Tandem appliance

    Directory of Open Access Journals (Sweden)

    Juhi Ansar

    2015-01-01

    Full Text Available Patients with a skeletal Class III malocclusion and maxillary deficiency can be treated successfully using a combined protraction facemask and alternate rapid maxillary expansions and contractions (Alt-RAMEC. However, due to poor patient compliance during facemask therapy there has been growing interest in intraoral appliances for correcting Class III malocclusion. The tandem traction bow appliance (TTBA is an intraoral appliance which has been used successfully for the treatment of growing Class III patients. This case report describes the management of a 10-year-old boy with a Class III malocclusion and maxillary deficiency treated with modified TTBA appliance.

  9. Management of pseudo Class III malocclusion--synergistic approach with fixed and functional appliance.

    Science.gov (United States)

    Kumar, Amit; Tandon, Pradeep; Singh, Gyan P

    2013-01-01

    Class III malocclusion has been divided into two subtypes: skeletal and pseudo-Class III. A pseudo Class III malocclusion should be treated as early as possible to reduce the functional shift of the mandible and increase maxillary arch length. A case of pseudo-Class III malocclusion was presented here. A 11-year-old boy came with an anterior cross bite, the treatment was done with Fixed appliance (Roth prescription) and Reverse Twin block therapy. This case demonstrated that an anterior cross bite was corrected after 10 months of treatment.

  10. Early treatment of Class III malocclusion by RME and modified Tandem appliance.

    Science.gov (United States)

    Ansar, Juhi; Maheshwari, Sandhya; Verma, Sanjeev Kumar; Singh, Raj Kumar

    2015-01-01

    Patients with a skeletal Class III malocclusion and maxillary deficiency can be treated successfully using a combined protraction facemask and alternate rapid maxillary expansions and contractions (Alt-RAMEC). However, due to poor patient compliance during facemask therapy there has been growing interest in intraoral appliances for correcting Class III malocclusion. The tandem traction bow appliance (TTBA) is an intraoral appliance which has been used successfully for the treatment of growing Class III patients. This case report describes the management of a 10-year-old boy with a Class III malocclusion and maxillary deficiency treated with modified TTBA appliance.

  11. Upper airway asymmetry in skeletal Class III malocclusions with mandibular deviation

    National Research Council Canada - National Science Library

    De-Hua Zheng; Xu-Xia Wang; Dan Ma; Yuan Zhou; Jun Zhang

    2017-01-01

    The purpose of this study was to investigate the relationship between bilateral differences of upper airway and mandibular morphologic patterns in subjects with skeletal Class III mandibular deviation...

  12. Cranial-base morphology in adults with skeletal Class III malocclusion.

    Science.gov (United States)

    Sanggarnjanavanich, Seetala; Sekiya, Toshiko; Nomura, Yoshiaki; Nakayama, Takahiro; Hanada, Nobuhiro; Nakamura, Yoshiki

    2014-07-01

    The objectives of this study were to clarify the characteristics of cranial-base morphology in adults with skeletal Class III malocclusion and investigate factors relating to the establishment of a skeletal Class III malocclusion. Initial lateral cephalograms of women were examined. Subjects with an ANB angle of 0° to 4°, normal overjet and overbite, and a Class I molar relationship were classified as Class I (n = 86). Those with an ANB angle less than -1°, a Wits appraisal less than 2 mm, a negative overjet, and a Class III molar relationship were the Class III group (n = 86) in this study. Angular, linear, and coordinate measurements were made. Multivariate analysis of variance and the Student t test were used to analyze significant differences between the 2 groups. Discriminant analysis, logistic regression analysis, and decision analysis were used to identify which cranial-base and maxillomandibular variables influenced the establishment of a skeletal Class III malocclusion. The Class III group had smaller values for NSBa, SeSBa, FH-SSe, and FH-SBa. Sphenoidale and basion were more inferior and anterior than those of the Class I group. There was no difference in the anterior and posterior cranial-base lengths between the groups. Greater mandibular length was the first major characteristic in the Class III group, followed by smaller values for SeSBa and NSBa. Cranial-base morphology in adults with a skeletal Class III malocclusion is different from that in a skeletal Class I malocclusion. Smaller cranial-base angles, steeper posterior cranial bases, more inferiorly positioned sphenoidale, and more anteriorly positioned basion are major characteristics of skeletal Class III malocclusions. These characteristics play important roles in the establishment of a skeletal Class III malocclusion. Copyright © 2014 American Association of Orthodontists. Published by Mosby, Inc. All rights reserved.

  13. Evaluation and Comparison of Intermaxillary Tooth Size Discrepancy among Class I, Class II Division 1, and Class III Subjects Using Bolton’s Analysis: An in vitro Study

    Science.gov (United States)

    Prasanna, A Lakshmi; Venkatramana, V; Aryasri, A Srikanth; Katta, Anil Kumar; Santhanakrishnan, K; Maheshwari, Uma

    2015-01-01

    Aim: The aim of the present study was to evaluation and comparison of intermaxillary tooth size discrepancy among Class I, Class II division 1, and Class III subjects using Bolton’s analysis. Materials and Methods: The pre-treatment casts were selected from the records of patients attending the Department of Orthodontics of Meenakshi Ammal Dental College, Chennai. The sample consists of 180 pre-treatment casts with both sexes evenly distributed with 60 casts in each type of malocclusion, i.e., Class I, Class II div 1, and Class III malocclusion. The sample was selected according to angles classification. All patients were Indian nationals, between the age group of 12 to 20 years and Bolton’s analysis done on all the casts. Results: Statistically no significant difference in all types of malocclusion except anterior Bolton’s discrepancy in Class III. Conclusion: Mean Bolton’s anterior ratio for angles Class III subjects was significantly greater than for Class I and Class II subjects. When Bolton’s overall ratio was compared there was no statistically significant difference among Class I, Class II div 1, and Class III malocclusions. PMID:26435619

  14. Improving Clinical Outcomes for Patients With Class III Heart Failure.

    Science.gov (United States)

    Shapiro, Melissa; Bires, Angela Macci; Waterstram-Rich, Kristen; Cline, Thomas W

    Heart failure (HF) is a serious medical problem in the United States and is placing a financial strain on the health care system. It is the leading cause of mortality and as the overall incidence continues to increase, so does the economic impact on the health care system. Innovative treatment options, in the form of disease management programs and implantable cardiac devices, such as the CorVue capable implantable cardioverter defibrillator (ICD) pacemaker, offer the promise of an enhanced quality of life and reduced mortality. Even with these advances, HF continues to be a challenge. Studies reviewing HF management programs have shown promising results. However, more studies are needed to determine which combination of HF management interventions has the greatest financial impact and yields the best patient outcomes. The objective of the research study was to compare 30-day readmission rates of patients implanted with the CorVue capable ICD pacemaker with patients with congestive heart failure (CHF) with no implanted device. The aim of the research focused on the usefulness of intrathoracic impedance monitoring alerts in guiding empirical treatment of patients with CHF to prevent HF readmissions. Methodology included a retrospective medical chart review, comparing 30-day readmission events among patients with class III CHF who received home health intervention with similar patients implanted with the CorVue ICD.

  15. Structure of the Epstein-Barr virus gp42 protein bound to the MHC class II recepter HLA-DR1

    Energy Technology Data Exchange (ETDEWEB)

    Mullen, M.; Haan, K.M.; Longnecker, R.; Jardetzky, T.

    2010-03-08

    Epstein-Barr virus (EBV) causes infectious mononucleosis, establishes long-term latent infections, and is associated with a variety of human tumors. The EBV gp42 glycoprotein binds MHC class II molecules, playing a critical role in infection of B lymphocytes. EBV gp42 belongs to the C-type lectin superfamily, with homology to NK receptors of the immune system. We report the crystal structure of gp42 bound to the human MHC class II molecule HLA-DR1. The gp42 binds HLA-DR1 using a surface site that is distinct from the canonical lectin and NK receptor ligand binding sites. At the canonical ligand binding site, gp42 forms a large hydrophobic groove, which could interact with other ligands necessary for EBV entry, providing a mechanism for coupling MHC recognition and membrane fusion.

  16. Sequences of 95 human MHC haplotypes reveal extreme coding variation in genes other than highly polymorphic HLA class I and II.

    Science.gov (United States)

    Norman, Paul J; Norberg, Steven J; Guethlein, Lisbeth A; Nemat-Gorgani, Neda; Royce, Thomas; Wroblewski, Emily E; Dunn, Tamsen; Mann, Tobias; Alicata, Claudia; Hollenbach, Jill A; Chang, Weihua; Shults Won, Melissa; Gunderson, Kevin L; Abi-Rached, Laurent; Ronaghi, Mostafa; Parham, Peter

    2017-05-01

    The most polymorphic part of the human genome, the MHC, encodes over 160 proteins of diverse function. Half of them, including the HLA class I and II genes, are directly involved in immune responses. Consequently, the MHC region strongly associates with numerous diseases and clinical therapies. Notoriously, the MHC region has been intractable to high-throughput analysis at complete sequence resolution, and current reference haplotypes are inadequate for large-scale studies. To address these challenges, we developed a method that specifically captures and sequences the 4.8-Mbp MHC region from genomic DNA. For 95 MHC homozygous cell lines we assembled, de novo, a set of high-fidelity contigs and a sequence scaffold, representing a mean 98% of the target region. Included are six alternative MHC reference sequences of the human genome that we completed and refined. Characterization of the sequence and structural diversity of the MHC region shows the approach accurately determines the sequences of the highly polymorphic HLA class I and HLA class II genes and the complex structural diversity of complement factor C4A/C4B It has also uncovered extensive and unexpected diversity in other MHC genes; an example is MUC22, which encodes a lung mucin and exhibits more coding sequence alleles than any HLA class I or II gene studied here. More than 60% of the coding sequence alleles analyzed were previously uncharacterized. We have created a substantial database of robust reference MHC haplotype sequences that will enable future population scale studies of this complicated and clinically important region of the human genome. © 2017 Norman et al.; Published by Cold Spring Harbor Laboratory Press.

  17. Molar heights and incisor inclinations in adults with Class II and Class III skeletal open-bite malocclusions.

    Science.gov (United States)

    Arriola-Guillén, Luis Ernesto; Flores-Mir, Carlos

    2014-03-01

    The aim of this research was to compare maxillary and mandibular molar heights and incisor inclinations in patients with skeletal open-bite Class II, patients with skeletal open-bite Class III, and an untreated control group. Pretreatment lateral cephalograms of 70 orthodontic patients (34 men, 36 women) between 16 and 40 years of age were examined. The sample was divided into 3 groups according to facial growth pattern and overbite. The control group (n = 25) included normodivergent Class I subjects with adequate overbite; the skeletal open-bite Class II group (n = 25) and the skeletal open-bite Class III group (n = 20) included hyperdivergent Class II or Class III subjects with negative overbite. Measurements considered were ANB angle, palatal and mandibular plane angles, maxillary incisor palatal plane angulation, and mandibular incisor mandibular plane angulation, as well as the distance from the palatal or the mandibular plane to the mesial cusp of the molars. Multivariate analysis of covariance and multivariate analysis of variance tests were used to determine the differences between the groups, followed by the Tukey post-hoc test. Additionally, the Mann-Whitney U test and Kruskall-Wallis test were performed. Significant differences in molar height were found (P palatal plane angulation was greater in the skeletal open-bite Class III group by approximately 6°. Mandibular incisor to mandibular plane angulation was 10° more lingual in the skeletal open-bite Class III group (P <0.001). The skeletal open-bite groups had greater molar heights than did the control group. The skeletal open-bite Class II group had more eruption of the mandibular molars. The maxillary incisors were more proclined and the mandibular incisors were more lingual in the skeletal open-bite Class III group. Copyright © 2014 American Association of Orthodontists. Published by Mosby, Inc. All rights reserved.

  18. Expression of HLA Class II Molecules in Humanized NOD.Rag1KO.IL2RgcKO Mice is Critical for Development and Function of Human T and B Cells

    Science.gov (United States)

    2011-05-17

    of the immune system is to protect against infections by eliciting specific antibodies that bind to and eliminate pathogens. Tetanus toxoid, a...titers of specific human IgG antibodies upon tetanus toxoid vaccination. Conclusions: Our study demonstrates the critical role of HLA class II... tetanus toxoid vaccination. Conclusions: Our study demonstrates the critical role of HLA class II molecules for development of functional human T cells

  19. The serodominant secreted effector protein of Salmonella, SseB, is a strong CD4 antigen containing an immunodominant epitope presented by diverse HLA class II alleles.

    Science.gov (United States)

    Reynolds, Catherine J; Jones, Claire; Blohmke, Christoph J; Darton, Thomas C; Goudet, Amelie; Sergeant, Ruhena; Maillere, Bernard; Pollard, Andrew J; Altmann, Daniel M; Boyton, Rosemary J

    2014-11-01

    Detailed characterization of the protective T-cell response in salmonellosis is a pressing unmet need in light of the global burden of human Salmonella infections and the likely contribution of CD4 T cells to immunity against this intracellular infection. In previous studies screening patient sera against antigen arrays, SseB was noteworthy as a serodominant target of adaptive immunity, inducing significantly raised antibody responses in HIV-seronegative compared with seropositive patients. SseB is a secreted protein, part of the Espa superfamily, localized to the bacterial surface and forming part of the translocon of the type III secretion system (T3SS) encoded by Salmonella pathogenicity island 2. We demonstrate here that SseB is also a target of CD4 T-cell immunity, generating a substantial response after experimental infection in human volunteers, with around 0.1% of the peripheral repertoire responding to it. HLA-DR/peptide binding studies indicate that this protein encompasses a number of peptides with ability to bind to several different HLA-DR alleles. Of these, peptide 11 (p11) was shown in priming of both HLA-DR1 and HLA-DR4 transgenic mice to contain an immunodominant CD4 epitope. Analysis of responses in human donors showed immunity focused on p11 and another epitope in peptide 2. The high frequency of SseB-reactive CD4 T cells and the broad applicability to diverse HLA genotypes coupled with previous observations of serodominance and protective vaccination in mouse challenge experiments, make SseB a plausible candidate for next-generation Salmonella vaccines. © 2014 The Authors. Immunology published by John Wiley & Sons Ltd.

  20. A vaccine encoding conserved promiscuous HIV CD4 epitopes induces broad T cell responses in mice transgenic to multiple common HLA class II molecules.

    Directory of Open Access Journals (Sweden)

    Susan Pereira Ribeiro

    Full Text Available Current HIV vaccine approaches are focused on immunogens encoding whole HIV antigenic proteins that mainly elicit cytotoxic CD8+ responses. Mounting evidence points toward a critical role for CD4+ T cells in the control of immunodeficiency virus replication, probably due to cognate help. Vaccine-induced CD4+ T cell responses might, therefore, have a protective effect in HIV replication. In addition, successful vaccines may have to elicit responses to multiple epitopes in a high proportion of vaccinees, to match the highly variable circulating strains of HIV. Using rational vaccine design, we developed a DNA vaccine encoding 18 algorithm-selected conserved, "promiscuous" (multiple HLA-DR-binding B-subtype HIV CD4 epitopes - previously found to be frequently recognized by HIV-infected patients. We assessed the ability of the vaccine to induce broad T cell responses in the context of multiple HLA class II molecules using different strains of HLA class II- transgenic mice (-DR2, -DR4, -DQ6 and -DQ8. Mice displayed CD4+ and CD8+ T cell responses of significant breadth and magnitude, and 16 out of the 18 encoded epitopes were recognized. By virtue of inducing broad responses against conserved CD4+ T cell epitopes that can be recognized in the context of widely diverse, common HLA class II alleles, this vaccine concept may cope both with HIV genetic variability and increased population coverage. The vaccine may thus be a source of cognate help for HIV-specific CD8+ T cells elicited by conventional immunogens, in a wide proportion of vaccinees.

  1. Transcriptional and Posttranscriptional Regulations of the HLA-G Gene

    Science.gov (United States)

    Castelli, Erick C.; Veiga-Castelli, Luciana C.; Yaghi, Layale; Donadi, Eduardo A.

    2014-01-01

    HLA-G has a relevant role in immune response regulation. The overall structure of the HLA-G coding region has been maintained during the evolution process, in which most of its variable sites are synonymous mutations or coincide with introns, preserving major functional HLA-G properties. The HLA-G promoter region is different from the classical class I promoters, mainly because (i) it lacks regulatory responsive elements for IFN-γ and NF-κB, (ii) the proximal promoter region (within 200 bases from the first translated ATG) does not mediate transactivation by the principal HLA class I transactivation mechanisms, and (iii) the presence of identified alternative regulatory elements (heat shock, progesterone and hypoxia-responsive elements) and unidentified responsive elements for IL-10, glucocorticoids, and other transcription factors is evident. At least three variable sites in the 3′ untranslated region have been studied that may influence HLA-G expression by modifying mRNA stability or microRNA binding sites, including the 14-base pair insertion/deletion, +3142C/G and +3187A/G polymorphisms. Other polymorphic sites have been described, but there are no functional studies on them. The HLA-G coding region polymorphisms might influence isoform production and at least two null alleles with premature stop codons have been described. We reviewed the structure of the HLA-G promoter region and its implication in transcriptional gene control, the structure of the HLA-G 3′UTR and the major actors of the posttranscriptional gene control, and, finally, the presence of regulatory elements in the coding region. PMID:24741620

  2. Expression of a cucumber class III chitinase and Nicotiana plumbaginifolia class I glucanase genes in transgenic potato plants

    NARCIS (Netherlands)

    Moravcikova, J.; Matusikova, I.; Libantova, J.; Bauer, M.; Mlynarova, L.

    2004-01-01

    The genes encoding for a cucumber class III chitinase and Nicotiana plumbaginifolia class I glucanase were co-introduced into Slovak potato (Solanum tuberosum L.) breeding line 116/86 using Agrobacterium tumefaciens. For both transgenes the number of integrated copies and level of RNA expression

  3. Role of metalloproteases in vaccinia virus epitope processing for transporter associated with antigen processing (TAP)-independent human leukocyte antigen (HLA)-B7 class I antigen presentation.

    Science.gov (United States)

    Lorente, Elena; García, Ruth; Mir, Carmen; Barriga, Alejandro; Lemonnier, François A; Ramos, Manuel; López, Daniel

    2012-03-23

    The transporter associated with antigen processing (TAP) translocates the viral proteolytic peptides generated by the proteasome and other proteases in the cytosol to the endoplasmic reticulum lumen. There, they complex with nascent human leukocyte antigen (HLA) class I molecules, which are subsequently recognized by the CD8(+) lymphocyte cellular response. However, individuals with nonfunctional TAP complexes or tumor or infected cells with blocked TAP molecules are able to present HLA class I ligands generated by TAP-independent processing pathways. Herein, using a TAP-independent polyclonal vaccinia virus-polyspecific CD8(+) T cell line, two conserved vaccinia-derived TAP-independent HLA-B*0702 epitopes were identified. The presentation of these epitopes in normal cells occurs via complex antigen-processing pathways involving the proteasome and/or different subsets of metalloproteinases (amino-, carboxy-, and endoproteases), which were blocked in infected cells with specific chemical inhibitors. These data support the hypothesis that the abundant cellular proteolytic systems contribute to the supply of peptides recognized by the antiviral cellular immune response, thereby facilitating immunosurveillance. These data may explain why TAP-deficient individuals live normal life spans without any increased susceptibility to viral infections.

  4. Cloning and functional characterization of a class III chitinase gene ...

    African Journals Online (AJOL)

    Analysis of the VvChiF III amino acid sequence showed that this gene corresponds to the Glyco-hydro-18 super family that consisting of a signal peptide with the length of 25 amino acids. Purified VvChiF III showed chitinase activity toward the soluble substrate, glycolchitin and antifungal activity against Botrytis cinerea.

  5. Tratamento ortopédico da Classe III em padrões faciais distintos Orthopedical treatment of Class III in different facial patterns

    Directory of Open Access Journals (Sweden)

    Paula Vanessa Pedron Oltramari

    2005-10-01

    Full Text Available A má oclusão de Classe III, de origem essencialmente esquelética, produz uma acentuada deformidade facial. A Classe III pode ser interceptada durante a fase de crescimento e desenvolvimento craniofacial mediante o uso de aparelhos ortopédicos. O crescimento mandibular, predominantemente endocondral na cartilagem condilar, obedece essencialmente ao controle genético. Portanto, os efeitos dos aparelhos ortopédicos que visam restringir o crescimento da mandíbula mostram-se limitados, o que conduz ao pobre prognóstico de tratamento precoce da Classe III determinada pelo prognatismo mandibular. Felizmente, o componente esquelético maxilar responde melhor à aplicação de forças ortopédicas, já que o crescimento ósseo intramembranoso mostra-se mais susceptível a influências extrínsecas ou ambientais. Deste modo, a Classe III morfologicamente definida pelo retrognatismo maxilar, privilegia-se com o tratamento ortopédico. Este trabalho discute o tratamento interceptivo da Classe III por meio da tração reversa da maxila em pacientes com padrões faciais distintos, apresentando dois casos clínicos, e ainda ressalta os aspectos atinentes a sua estabilidade.The Class III malocclusion, essentially of skeletal origin, produces an accentuated facial deformity. These malocclusion can be intercepted during the growth phase and craniofacial development by the use of orthopedical appliances. The mandibular growth, predominantly endocondral at the condilar cartilage, follows a genetic control essentially. Therefore, the effect of orthopedical appliances that aim restriction in the jaw's growth are shown limited, what leads to a poor prognostic of precocious treatment of the Class III determined by a mandibular prognathism. Fortunately, the skeletal maxillary component answers better to the application of orthopedical forces, since the growth of intramembranous bone is shown more susceptible to extrinsic influences. This way, the Class III

  6. Differences in promoter DNA methylation and mRNA expression of individual alleles of the HLA class II DQA1 gene.

    Science.gov (United States)

    Zajacova, Marta; Kotrbova-Kozak, Anna; Cepek, Pavel; Cerna, Marie

    2015-10-01

    Extensive polymorphism of HLA class II genes is not restricted to the coding region of the gene. It extends also to the linked promoter region, where it forms the basis for different levels of individual allele's expression. Differential expression of HLA class II alleles can shape an immune response and influence the risk of developing autoimmune disease. In addition to genetic variability, variation in epigenetic modifications, including DNA methylation, can be another cause of the uneven expression of individual alleles. We aimed to analyze the DNA methylation of promoter sequences and the levels of expression of individual DQA1 gene alleles, interallelic variation of these two characteristics and the relationship between them. The 60 healthy donors included into study were HLA-DRB1, HLA-DQB1 and HLA-DQA1 genotyped using PCR-SSP. Genomic DNA was treated by sodium bisulfite and the target segment in the HLA-DQA1 gene promoter was PCR amplified. PCR product was cloned into Escherichia coli and individual clones were sequenced. Transcripts of individual DQA1 alleles in peripheral blood leukocytes were quantified by Real-Time PCR. In this study, we have described detailed DNA methylation profile of promoter area of DQA1 gene alleles. The overall promoter methylation is increased for DQA1*02:01 and DQA1*04:01 alleles, on the other side, DQA1*05:01 allele shows decreased methylation level. Our results suggest that there are only minor interindividual differences in DRA-normalized expression level of specific allele. Furthermore, expression levels of individual alleles followed DQA1*03>*01:03 (in DRB1*13-DQA1*01:03-DQB1*06:03 haplotype)>*01:01,*05:05, and DQA1*03>*02:01>*05:05 hierarchy. The statistically significantly most expressed allele, DQA1*03, comprises part of DQ8 molecule, which is commonly linked to autoimmune diseases. A clear relationship between promoter DNA methylation and mRNA expression level of the DQA1 gene could not be identified. Copyright © 2015

  7. Oral Impacts on Quality of Life in Adult Patients with Class I, II and III Malocclusion.

    Science.gov (United States)

    Javed, Omair; Bernabé, Eduardo

    2016-01-01

    To compare the social impact of malocclusion on quality of life between adult patients with Angle Class I, II and III malocclusion. A total of 222 adult patients (139, 42 and 41 with Angle Class I, II and III malocclusion, respectively) were recruited voluntarily from those attending the Orthodontic Clinic of Khyber College of Dentistry in Pesh awar, Pakistan. Participants were asked to complete the Urdu version of the short form of the Oral Health Impact Profile (OHIP-14), which was previously validated for this study. Multivariate analysis of variance (MANOVA) was used to compare the seven OHIP-14 domains scores and the total score between patients with malocclusion Class I, II and III. Adults with Class III malocclusion had a significantly higher OHIP-14 total score than those with Class I malocclusion (a mean difference of 5 units between groups), but there were no differences between other Angle malocclusion groups. In addition, adults with Class III malocclusion reported greater impacts on the three OHIP-14 disability domains (physical, psychological and social) than those with Class I malocclusion. No significant interactions with sex and age were found. These findings suggest that adult patients with Class III malocclusion had a poorer quality of life than those with Class I malocclusion. Differences were mainly found in the physical, psychological and social disability domains of the OHIP-14 instrument.

  8. Civilization III and Whole-Class Play in High School Social Studies

    Science.gov (United States)

    Lee, John K.; Probert, Jeffrey

    2010-01-01

    This study examined an 11th grade high school class as they played the game Civilization III. Over nine class sessions students played the game in support of other activities related to several predetermined and emergent topics in U. S. history. Gameplay was whole-class oriented and involved students taking turns at the computer controlling…

  9. Tooth size discrepancies in Class II division 1 and Class III malocclusion requiring surgical-orthodontic or orthodontic treatment.

    Science.gov (United States)

    McSwiney, Timothy P; Millett, Declan T; McIntyre, Grant T; Barry, Mark K; Cronin, Michael S

    2014-06-01

    To compare mean anterior (AR) and mean overall (OR) tooth size ratios, prevalence of clinically significant tooth size discrepancies (TSDs) and correlation between AR and OR in subjects with Class II division 1 and Class III malocclusion treated by surgical-orthodontic or orthodontic means. Retrospective, cross-sectional. State-funded and private clinics. From pre-treatment cohorts of 770 surgical and 610 non-surgical subjects, Class II division 1 and Class III malocclusion groups were identified with 60 surgical and 60 non-surgical subjects, comprising 30 males and 30 females, in each. AR and OR were calculated by landmarking digital models. Differences in AR and OR and their relationship were analysed using two-way analysis of variance (ANOVA) and a correlation coefficient, respectively. The proportions of the surgical and non-surgical groups with a TSD were assessed using logistic regression. Intra-examiner reproducibility involved re-landmarking 30 randomly selected image sets and differences in ARs and ORs were compared using a paired t-test. Random error was assessed using the intraclass correlation coefficient (ICC). Analyses were performed using SAS (SAS Institute Inc., Cary, NC, USA) at the 5% level of significance. There were no statistically significant differences associated with the measurement of either the mean AR (P = 0·913) or the mean OR (P = 0·874). ICC values were very high (AR = 0·95; OR = 0·90). Differences existed between both Class II and Class III surgical (AR: PClass II and Class III surgical groups (23·3%). In the cohort examined: AR and OR differed significantly for malocclusion groups. The prevalence of clinically significant TSDs did not differ significantly between surgical and non-surgical groups although the highest percentage of clinically significant TSDs was recorded for AR in Class II and Class III surgical cases. AR and OR were closely related. © 2014 British Orthodontic Society.

  10. Contribution of KIR genes, HLA class I ligands, and KIR/HLA class I ligand combinations on the genetic predisposition to celiac disease and coexisting celiac disease and type 1 diabetes mellitus.

    Science.gov (United States)

    Akar, H Haluk; Patiroglu, Turkan; Sevinc, Eylem; Aslan, Duran; Okdemir, Deniz; Kurtoglu, Selim

    2015-09-01

    There are some common genetic features between celiac disease (CD) and diabetes mellitus type 1 (DM). However, the genetic risk factors have not been fully clarified for CD and the co-occurrence of CD and DM. KIR (killer immunoglobulin-like receptor) genes regulate the cytolitic activity of NK-cells and T lymphocytes. The aim of this study is to evaluate the contribution of KIR genes, KIR ligands, and combinations of KIR/ KIR ligands on the genetic predisposition to CD and co-occurrence of CD and DM. Forty six patients with CD (n = 46), 20 patients with CD+DM (n = 20), and 60 healthy controls (n = 60) were included in this study. KIR genes and KIR ligands were investigated with PCR-SSOP and PCR-SSP in all subjects, respectively. This study showed that while the telomeric KIR genes (2DS5 and 3DS1), and combinations of 3DS1+HLA-BBw4-Thrand 3DS1+HLA-BBw4-Iso- (p genes, C1 ligand, and combinations of 3DS1+HLA-BBw4-Thr- and 3DS1+HLA-BBw4-Iso- (p = 0.002, p = 0.004, p = 0.036, p genes, KIR ligands, and KIR/KIR ligand interactions may be responsible for a predisposition to CD and the coexistence of CD and DM. For development of coexisting CD and DM, the 2DS5 and 3DS1 genes, C1 ligand, and combinations of 3DS1+HLA-BBw4-Thr- and 3DS1+HLA-BBw4-Iso- were found to be risk factors.

  11. Early class III management in deciduous dentition using reverse twin block

    Directory of Open Access Journals (Sweden)

    S S Sargod

    2013-01-01

    Full Text Available Class III malocclusion poses a challenging dilemma for the clinician because these children have of growth patterns that differ from that of children with class I malocclusion. The mandible grows more rapidly than the maxilla, exacerbating the class III malocclusion as the child go through adolescence. Ever since Clark described a version of the twin block, it has steadily gained popularity in the management of early class III malocclusion in children. However, not many cases are reported in the literature on its use in deciduous dentition. This article tries to provide an insight into the reverse twin block appliance and reports two cases of early class III malocclusion treated using reverse twin block.

  12. Glenoid fossa position in Class III malocclusion associated with mandibular protrusion.

    Science.gov (United States)

    Innocenti, Cristina; Giuntini, Veronica; Defraia, Efisio; Baccetti, Tiziano

    2009-04-01

    Our aim in this study was to investigate the position of the glenoid fossa in subjects with Class III malocclusion associated with mandibular protrusion to better clarify the role of this craniofacial component in Class III skeletal disharmony. A sample of 30 subjects, aged 8 years +/- 6 months, with skeletal and dental Class III malocclusion associated with mandibular protrusion, normal skeletal vertical relationships, and normal mandibular dimensions, was compared with a control group of 33 subjects with skeletal and dental Class I relationships. The comparisons between the Class III group and the control group on the cephalometric measures for the assessment of glenoid fossa position were performed with the Mann-Whitney U test at P mandibular protrusion. An effective measurement to evaluate glenoid fossa position in craniofacial relationships is the cephalometric distance from the glenoid fossa to the frontomaxillary-nasal suture.

  13. Diversity of extended HLA-DRB1 haplotypes in the Finnish population.

    Science.gov (United States)

    Wennerström, Annika; Vlachopoulou, Efthymia; Lahtela, L Elisa; Paakkanen, Riitta; Eronen, Katja T; Seppänen, Mikko; Lokki, Marja-Liisa

    2013-01-01

    The Major Histocompatibility Complex (MHC, 6p21) codes for traditional HLA and other host response related genes. The polymorphic HLA-DRB1 gene in MHC Class II has been associated with several complex diseases. In this study we focus on MHC haplotype structures in the Finnish population. We explore the variability of extended HLA-DRB1 haplotypes in relation to the other traditional HLA genes and a selected group of MHC class III genes. A total of 150 healthy Finnish individuals were included in the study. Subjects were genotyped for HLA alleles (HLA-A, -B, -DRB1, -DQB1, and -DPB1). The polymorphism of TNF, LTA, C4, BTNL2 and HLA-DRA genes was studied with 74 SNPs (single nucleotide polymorphism). The C4A and C4B gene copy numbers and a 2-bp silencing insertion at exon 29 in C4A gene were analysed with quantitative genomic realtime-PCR. The allele frequencies for each locus were calculated and haplotypes were constructed using both the traditional HLA alleles and SNP blocks. The most frequent Finnish A∼B∼DR -haplotype, uncommon in elsewhere in Europe, was A*03∼B*35∼DRB1*01∶01. The second most common haplotype was a common European ancestral haplotype AH 8.1 (A*01∼B*08∼DRB1*03∶01). Extended haplotypes containing HLA-B, TNF block, C4 and HLA-DPB1 strongly increased the number of HLA-DRB1 haplotypes showing variability in the extended HLA-DRB1 haplotype structures. On the contrary, BTNL2 block and HLA-DQB1 were more conserved showing linkage with the HLA-DRB1 alleles. We show that the use of HLA-DRB1 haplotypes rather than single HLA-DRB1 alleles is advantageous when studying the polymorphisms and LD patters of the MHC region. For disease association studies the HLA-DRB1 haplotypes with various MHC markers allows us to cluster haplotypes with functionally important gene variants such as C4 deficiency and cytokines TNF and LTA, and provides hypotheses for further assessment. Our study corroborates the importance of studying population-specific MHC

  14. Camouflage treatment of skeletal Class III malocclusion with multiloop edgewise arch wire and modified Class III elastics by maxillary mini-implant anchorage.

    Science.gov (United States)

    He, Shushu; Gao, Jinhui; Wamalwa, Peter; Wang, Yunji; Zou, Shujuan; Chen, Song

    2013-07-01

    To evaluate the effect of the multiloop edgewise arch wire (MEAW) technique with maxillary mini-implants in the camouflage treatment of skeletal Class III malocclusion. Twenty patients were treated with the MEAW technique and modified Class III elastics from the maxillary mini-implants. Twenty-four patients were treated with MEAW and long Class III elastics from the upper second molars as control. Lateral cephalometric radiographs were obtained and analyzed before and after treatment, and 1 year after retention. Satisfactory occlusion was established in both groups. Through principal component analysis, it could be concluded the anterior-posterior dental position, skeletal sagittal and vertical position, and upper molar vertical position changed within groups and between groups; vertical lower teeth position and Wits distance changed in the experimental group and between groups. In the experimental group, the lower incisors tipped lingually 2.7 mm and extruded 2.4 mm. The lingual inclination of the lower incisors increased 3.5°. The mandibular first molars tipped distally 9.1° and intruded 0.4 mm. Their cusps moved 3.4 mm distally. In the control group, the upper incisors proclined 3°, and the upper first molar extruded 2 mm. SN-MP increased 1.6° and S-Go/N-ME decreased 1. The MEAW technique combined with modified Class III elastics by maxillary mini-implants can effectively tip the mandibular molars distally without any extrusion and tip the lower incisors lingually with extrusion to camouflage skeletal Class III malocclusions. Clockwise rotation of the mandible and further proclination of upper incisors can be avoided. The MEAW technique and modified Class III elastics provided an appropriate treatment strategy especially for patients with high angle and open bite tendency.

  15. HLA-G expression in placenta in relation to HLA-G genotype and polymorphisms

    DEFF Research Database (Denmark)

    Hviid, Thomas Vauvert F; Larsen, Lise Grupe; Hoegh, Anne Mette

    2004-01-01

    PROBLEM: The expression of the non-classical human leukocyte antigen (HLA) class Ib gene, HLA-G, seems to be important at the feto-maternal interface. The HLA-G molecule is almost monomorphic and expressed in both membrane-bound and soluble isoforms. It has been shown to inhibit natural killer cell...... -mediated lysis and influence cytokine expression. HLA-G gene polymorphism has been linked to differences in gene expression profile of alternatively spliced HLA-G transcripts and levels of specific HLA-G messenger RNA (mRNA) isoforms. Furthermore, aberrant HLA-G expression has been reported in preeclamptic...... placentas. On this background it is of general interest to further elucidate any associations between HLA-G polymorphism and protein expression. METHODS: We have investigated HLA-G protein expression by immunohistochemistry in HLA-G genotyped placentas from term. HLA-G mRNA expression in preeclamptic...

  16. WITHDRAWN: Low level laser therapy (Classes III) for treating osteoarthritis.

    Science.gov (United States)

    Brosseau, L; Robinson, V; Wells, G; Debie, R; Gam, A; Harman, K; Morin, M; Shea, B; Tugwell, P

    2007-07-18

    Osteoarthritis (OA) affects a large portion of the population. Low Level Laser Therapy (LLLT) is a light source that generates extremely pure light, of a single wavelength. The effect is not thermal, but rather related to photochemical reactions in the cells. LLLT was introduced as an alternative non-invasive treatment for OA about 30 years ago, but its effectiveness has to be examined more closely, especially in the treatment of OA. To assess the effectiveness of class III LLLT for osteoarthritis when irradiation is directed at the osteoarthritic joint capsule. Searches were conducted in the following databases: MEDLINE, EMBASE, the Cochrane Musculoskeletal registry, the Rehabilitation and Related Therapies field registry and the Cochrane Controlled Trials Register up to May, 2005. Following an a prior protocol, only controlled clinical trials of LLLT for the treatment of patients with a clinical diagnosis of OA were eligible. Abstracts lacking data were excluded unless further data could be obtained from the authors. Two reviewers independently selected trials and extracted data using predetermined forms. A fixed effects model was used throughout for continuous variables, except where heterogeneity existed; in which case, a random effects model was used. Results were analyzed as weighted mean differences (WMD) with 95% confidence intervals (CI), whereas the difference between the treatment and control groups was weighted by the inverse of the variance. Standardized mean differences (SMD) were calculated by dividing the difference between treatment and control by the baseline variance, and were used in the analysis of pain because different scales were used to measure it. Dichotomous outcomes were analyzed with relative risk (RR). Eight trials were included with 233 patients randomized to laser and 172 patients to placebo laser. Treatment duration ranged from two to six weeks. Pain was assessed in seven trials. When the results were pooled from different pain

  17. HLA class II alleles in the Otomi population of the Mezquital Valley: a genetic approach to the history of interethnic migrations in the Mexican Central Plateau.

    Science.gov (United States)

    Juárez-Martín, Ana Itzel; González-Sobrino, Blanca Zoila; Olvera, Ángel Eduardo Camarena; Falfán-Valencia, Ramcés

    2014-01-01

    From a historical and genetic point of view, the Otomi of the Mezquital Valley are a frontier people that have played an important role in the population dynamics of the Mexican Central Plateau. Due to the antiquity of their presence in the area, the Otomi may be bearers of ancient genetic variability, shared mainly today with other groups belonging to the Otomanguean linguistic family and with the Nahua. In this study we analyzed the HLA class II allele frequencies reported in Mexican indigenous populations, in order to provide an intraregional-level historical perspective of the genetic relationships between the Otomi of the Mezquital Valley and indigenous populations from other regions of Mexico. We examined genetic variation in HLA-DRB1 and -DQB1 loci in 66 nonrelated individuals belonging to seven indigenous communities from the Ixmiquilpan municipality in the Mezquital Valley, in the State of Hidalgo, Mexico. The variability of the HLA-DRB1 gene among the Otomi of the Mezquital Valley was mainly concentrated in five alleles: -DRB1*08:02 (31.06%), -DRB1*04:07 (25.77%), -DRB1*14:06 (7.55%), -DRB1*14:02 (6.06%), and -DRB1*16:02 (4.55%); these alleles have been previously described in other indigenous populations. The most frequent alleles at the HLA-DQB1 locus were -DQB1*03:02 (34.09%), -DQB1*04:02 (31.03%), and -DQB1*03:01 (19.7%). Furthermore, the HLA-DQB1*02:02 allele was found in the Otomi group with a frequency of 2.27%; this allele has not been reported in Mexican indigenous populations. In conclusion, the genetic constitution of the Otomi population is intermediate to the northern groups and the genetic variability shared by the peoples of the central regions of Mexico. Furthermore, HLA-DRB1 and -DQB1 allelic variability among the Otomi provides insight into the historical processes implied in the biological admixture with European, Asian, and African populations as well as in the admixture with the population of Mexico City associated with long

  18. 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

  19. Extended LTA, TNF, LST1 and HLA gene haplotypes and their association with rubella vaccine-induced immunity.

    Directory of Open Access Journals (Sweden)

    Inna G Ovsyannikova

    2010-07-01

    Full Text Available Recent studies have suggested the importance of HLA genes in determining immune responses following rubella vaccine. The telomeric class III region of the HLA complex harbors several genes, including lymphotoxin alpha (LTA, tumor necrosis factor (TNF and leukocyte specific transcript -1 (LST1 genes, located between the class I B and class II DRB1 loci. Apart from HLA, little is known about the effect of this extended genetic region on HLA haplotypic backgrounds as applied to immune responses.We examined the association between immune responses and extended class I-class II-class III haplotypes among 714 healthy children after two doses of rubella vaccination. These extended haplotypes were then compared to the HLA-only haplotypes. The most significant association was observed between haplotypes extending across the HLA class I region, ten-SNP haplotypes, and the HLA class II region (i.e. A-C-B-LTA-TNF-LST1-DRB1-DQA1-DQB1-DPA1-DPB1 and rubella-specific antibodies (global p-value of 0.03. Associations were found between both extended A*02-C*03-B*15-AAAACGGGGC-DRB1*04-DQA1*03-DQB1*03-DPA1*01-DPB1*04 (p = 0.002 and HLA-only A*02-C*03-B*15-DRB1*04-DQA1*03-DQB1*03-DPA1*01-DPB1*04 haplotypes (p = 0.009 and higher levels of rubella antibodies. The class II HLA-only haplotype DRB1*13-DQA1*01-DQB1*06-DPA1*01-DPB1*04 (p = 0.04 lacking LTA-TNF-LST1 SNPs was associated with lower rubella antibody responses. Similarly, the class I-class II HLA-only A*01-C*07-B*08-DRB1*03-DQA1*05-DQB1*02-DPA1*01-DPB1*04 haplotype was associated with increased TNF-alpha secretion levels (p = 0.009. In contrast, the extended AAAACGGGGC-DRB1*01-DQA1*01-DQB1*05-DPA1*01-DPB1*04 (p = 0.01 haplotype was found to trend with decreased rubella-specific IL-6 secretion levels.These data suggest the importance of examining both HLA genes and genes in the class III region as part of the extended haplotypes useful in understanding genomic drivers regulating immune responses to rubella

  20. Extended LTA, TNF, LST1 and HLA Gene Haplotypes and Their Association with Rubella Vaccine-Induced Immunity

    Science.gov (United States)

    Ovsyannikova, Inna G.; Vierkant, Robert A.; Pankratz, V. Shane; Jacobson, Robert M.; Poland, Gregory A.

    2010-01-01

    Background Recent studies have suggested the importance of HLA genes in determining immune responses following rubella vaccine. The telomeric class III region of the HLA complex harbors several genes, including lymphotoxin alpha (LTA), tumor necrosis factor (TNF) and leukocyte specific transcript -1 (LST1) genes, located between the class I B and class II DRB1 loci. Apart from HLA, little is known about the effect of this extended genetic region on HLA haplotypic backgrounds as applied to immune responses. Methodology/Principal Findings We examined the association between immune responses and extended class I-class II-class III haplotypes among 714 healthy children after two doses of rubella vaccination. These extended haplotypes were then compared to the HLA-only haplotypes. The most significant association was observed between haplotypes extending across the HLA class I region, ten-SNP haplotypes, and the HLA class II region (i.e. A-C-B-LTA-TNF-LST1-DRB1-DQA1-DQB1-DPA1-DPB1) and rubella-specific antibodies (global p-value of 0.03). Associations were found between both extended A*02-C*03-B*15-AAAACGGGGC-DRB1*04-DQA1*03-DQB1*03-DPA1*01-DPB1*04 (p = 0.002) and HLA-only A*02-C*03-B*15-DRB1*04-DQA1*03-DQB1*03-DPA1*01-DPB1*04 haplotypes (p = 0.009) and higher levels of rubella antibodies. The class II HLA-only haplotype DRB1*13-DQA1*01-DQB1*06-DPA1*01-DPB1*04 (p = 0.04) lacking LTA-TNF-LST1 SNPs was associated with lower rubella antibody responses. Similarly, the class I-class II HLA-only A*01-C*07-B*08-DRB1*03-DQA1*05-DQB1*02-DPA1*01-DPB1*04 haplotype was associated with increased TNF-α secretion levels (p = 0.009). In contrast, the extended AAAACGGGGC-DRB1*01-DQA1*01-DQB1*05-DPA1*01-DPB1*04 (p = 0.01) haplotype was found to trend with decreased rubella-specific IL-6 secretion levels. Conclusions/Significance These data suggest the importance of examining both HLA genes and genes in the class III region as part of the extended haplotypes useful in

  1. Association between antinuclear antibodies and the HLA class II locus and heterogeneous characteristics of staining patterns: the Nagahama study.

    Science.gov (United States)

    Terao, Chikashi; Ohmura, Koichiro; Yamada, Ryo; Kawaguchi, Takahisa; Shimizu, Masakazu; Tabara, Yasuharu; Takahashi, Meiko; Setoh, Kazuya; Nakayama, Takeo; Kosugi, Shinji; Sekine, Akihiro; Matsuda, Fumihiko; Mimori, Tsuneyo

    2014-12-01

    While antinuclear antibodies (ANAs) are observed in healthy populations as well as in patients with autoimmune diseases such as systemic lupus erythematosus (SLE), the detailed genetic background of ANAs has remained unclear. We undertook this study to identify the genetic determinants of ANAs in the general population in order to elucidate the underlying mechanisms of ANA production and to distinguish disease susceptibility genes from ANA production genes. A total of 9,575 Japanese volunteers were registered, and their ANA levels were quantified using indirect immunofluorescence to analyze correlates of ANA positivity. Genetic studies were performed using 7,148 of the 9,575 subjects. We performed a genome-wide association study using 3,185 subjects genotyped for 303,506 single-nucleotide polymorphisms (SNPs), followed by a replication study of 3,963 subjects. HLA-DRB1 and HLA-DQB1 alleles were imputed, and associations between ANA positivity and the SNPs or the HLA alleles associated with SLE were analyzed. Female sex and old age were associated with ANA positivity, except for the nucleolar pattern. The T allele of rs2395185 in the HLA locus, which was in moderate linkage disequilibrium with HLA-DRB1*0405, was significantly associated with ANA positivity (P = 1.3 × 10(-11) ). The T allele of rs2395185 displayed increasing effects on the frequency of speckled and homogeneous patterns (P = 7.5 × 10(-12) and P = 2.2 × 10(-11) , respectively) but decreasing effects on the frequency of the nucleolar pattern (P = 0.0045). The 7 SNPs and 4 HLA-DRB1 alleles associated with SLE did not display strong associations with ANA positivity. SNP rs2395185 linked with HLA-DRB1*0405 is a genetic determinant of ANA production in the Japanese population. Overlapping of loci for susceptibility to SLE and to ANA positivity was limited. The nucleolar pattern showed different associations from other staining patterns, both with correlates of ANA positivity and with the HLA locus

  2. Assessment of Upper and Lower Pharyngeal Airway Width in Skeletal Class I, II and III Malocclusions

    Directory of Open Access Journals (Sweden)

    Shalu Jain

    2014-01-01

    Full Text Available Introduction: There is a close relationship between the dimensions of airway and the sagittal skeletal malocclusion which makes it reasonable to expect that width of airway is a reflection of determining patency of airway in different skeletal malocclusion groups. So, aim of this study was to assess the upper and lower pharyngeal airway width in skeletal Class I, II and III malocclusion groups and also to evaluate sexual dimorphism in western Uttar Pradesh population. Materials and methods: A sample of 150 subjects in the age group of 18 to 25 years, from Western Uttar Pradesh adult population was selected on the basis of skeletal Class I, II and III malocclusion. Digital lateral cephalograms were taken in natural head position. Nine variables were selected which included four upper and five lower pharyngeal airway variables. Results: Upper and lower pharynx showed statistical significant difference among the skeletal Class I, II and III malocclusion and also between males and females. Conclusion: Wider upper and lower pharyngeal airway width was seen in males than in females in both skeletal Class I as well as Class III malocclusion groups respectively. Skeletal Class III malocclusion subjects had the widest airway width as compared to skeletal Class I malocclusion group. Skeletal Class II malocclusion, airway width was found to be narrowest.

  3. Early class III occlusal tendency in children and its selective management

    Directory of Open Access Journals (Sweden)

    Kapur A

    2008-09-01

    Full Text Available Class III malocclusion may develop in children as a result of an inherent growth abnormality, i.e., true class III malocclusion, or as a result of premature occlusal contacts causing forward functional shift of the mandible, which is known as pseudo class III malocclusion. These cases, if not treated at the initial stage of development, interfere with normal growth of the skeletal bases and may result in severe facial deformities. The treatment should be carried out as early as possible with the aim of permitting normal growth. This paper deals with the selection of an appropriate treatment approach from the various current options available for early intervention in children developing class III occlusal tendencies; the different clinical features are depicted in the three case reports.

  4. Reverse twin block for interceptive management of developing class III malocclusion.

    Science.gov (United States)

    Mittal, Meenu; Singh, Harpreet; Kumar, Ashok; Sharma, Poonam

    2017-01-01

    Early correction of developing class III malocclusions remains a complex challenge. Treatment approaches for these young patients have been directed at growth modification. Encouraging outcomes have been reported with the use of Class III functional appliances including reverse twin block (RTB) appliance. The present paper tries to provide an insight into RTB appliance used for successful interceptive management of developing class III malocclusion in two children. RTBs were fabricated with bite registered in the position of maximum possible retrusion of mandible with interincisal clearance of 2 mm and vertical clearance of 5 mm in the buccal segments. Anterior crossbite was corrected, and there was a marked improvement in facial appearance of the children. RTB can be a viable and effective functional appliance treatment modality for early management of developing class III malocclusion.

  5. Reverse twin block for interceptive management of developing class III malocclusion

    Directory of Open Access Journals (Sweden)

    Meenu Mittal

    2017-01-01

    Full Text Available Early correction of developing class III malocclusions remains a complex challenge. Treatment approaches for these young patients have been directed at growth modification. Encouraging outcomes have been reported with the use of Class III functional appliances including reverse twin block (RTB appliance. The present paper tries to provide an insight into RTB appliance used for successful interceptive management of developing class III malocclusion in two children. RTBs were fabricated with bite registered in the position of maximum possible retrusion of mandible with interincisal clearance of 2 mm and vertical clearance of 5 mm in the buccal segments. Anterior crossbite was corrected, and there was a marked improvement in facial appearance of the children. RTB can be a viable and effective functional appliance treatment modality for early management of developing class III malocclusion.

  6. Craniofacial changes in patients with Class III malocclusion treated with the RAMPA system.

    Science.gov (United States)

    Mitani, Yasushi; Banabilh, Saeed M; Singh, G Dave

    2010-01-01

    The underlying etiology of Class III malocclusion may be associated with cranial base morphology. The aim of this study is to test the efficacy of a Right-Angled Maxillary Protraction Appliance (RAMPA) System in Asian subjects with Class III malocclusions. 27 homologous landmarks were digitized from lateral cephalographs for 10 pre-pubertal Japanese children (mean age 95 months) with skeletal Class III malocclusion prior to and after RAMPA treatment. The mean, pre- and post-treatment craniofacial configurations were computed using Procrustes superimposition, and subjected to principal components analysis (PCA), and finite-element analysis (FEA). The mean treatment time was 22.5 months. All patients showed significant craniofacial change with correction of anterior and/or posterior crossbite. The mean, pre- and post-treatment craniofacial configurations were statistically different when tested using PCA (p Class III malocclusions.

  7. New model for surgical and nonsurgical therapy in adults with Class III malocclusion.

    Science.gov (United States)

    Kochel, Janka; Emmerich, Stefanie; Meyer-Marcotty, Philipp; Stellzig-Eisenhauer, Angelika

    2011-02-01

    Not all adult Class III malocclusion patients are candidates for surgical correction. In patient assessment and selection, major issues remain regarding diagnosis and treatment planning. The purpose of this investigation was to ascertain whether adding a transverse parameter to a discriminant analysis could improve the classification of adults with Class III malocclusion into 2 groups of patients: those who can effectively be treated by orthodontic therapy and those who require orthognathic surgery. Cephalograms, plaster casts, and extraoral photos of 69 adults with Class III malocclusion were analyzed. A discriminant analysis was performed to identify the variables that best separate the 2 groups. Stepwise variable selection resulted in a new, highly significant (P Class III malocclusion patients with surgical requirements. Copyright © 2011 American Association of Orthodontists. Published by Mosby, Inc. All rights reserved.

  8. Zygomatic miniplates for skeletal anchorage in orthopedic correction of Class III malocclusion: A controlled clinical trial

    National Research Council Canada - National Science Library

    Erdal Bozkaya; Alime Sema Yüksel; Süleyman Bozkaya

    2017-01-01

    Objective: To evaluate the effects of facemask therapy, which was anchored from the zygomatic buttresses of the maxilla by using two miniplates, in skeletal Class III patients with maxillary deficiency. Methods...

  9. [Magnetic resonance imaging assessment of the lateral pterygoid muscle in Class III malocclusion subjects].

    Science.gov (United States)

    Liu, Yue-hua; Yang, Xiao-jiang; Gao, Xiao-hui; Li, Yuan

    2012-01-01

    To analyze the relationship between Class III malocclusion and pathological changes in temporomandibular joint (TMJ) structures using magnetic resenonce imaging (MRI). Twenty-four Class III malocclusion adult patients and 10 normal control cases were included in the study. The characteristics of lateral pertygoid muscle (LPM) in the sample group and the control group were assessed. More pathological changes of LPM were found in Class III malocclusion adult patients (36 TMJ). The changes included hypertrophy, atrophy and contracture. And there was no relation between the pathological changes of LPM and the symptom of temporomandibular disorders (TMD). The frequency of pathological changes of LPM was greater in patients with Class III malocclusion than in the control group.

  10. Facemask Therapy and Lower Incisor Extraction in Mild Skeletal Class III Malocclusion

    Directory of Open Access Journals (Sweden)

    Poornima Ksheerasagara

    2014-01-01

    Full Text Available Class III malocclusions may be made up of different combinations of skeletal and dentoalveolar components. Consideration of the various components is essential to understanding the underlying causes of the discrepancy which, in turn, is essential in choosing the appropriate treatment. Protraction of facemask therapy has been successful in the early treatment of Class III patients with maxillary deficiencies. However 25 to 33% of the treated patients reverted to an anterior crossbite when they reach their pubertal growth spurt. This case report describes management of mild Class III malocclusion with facemask therapy to address deficient maxilla and lower incisor extraction to relieve lower anterior crowing and proclination. Achieving positive over jet prevents relapse which are high in cases of Class III malocclusions with anterior edge to edge bite.

  11. Influence of surgical orthodontic treatment on masticatory function in skeletal Class III patients.

    Science.gov (United States)

    Kubota, T; Yagi, T; Tomonari, H; Ikemori, T; Miyawaki, S

    2015-10-01

    Skeletal Class III patients exhibit malocclusion characterised by Angle Class III and anterior crossbite, and their occlusion shows total or partially lateral crossbite of the posterior teeth. Most patients exhibit lower bite force and muscle activity than non-affected subjects. While orthognathic surgery may help improve masticatory function in these patients, its effects have not been fully elucidated. The aims of the study were to evaluate jaw movement and the electromyographic (EMG) activity of masticatory muscles before and after orthognathic treatment in skeletal Class III patients in comparison with control subjects with normal occlusion. Jaw movement variables and EMG data were recorded in 14 female patients with skeletal Class III malocclusion and 15 female controls with good occlusion. Significant changes in jaw movement, from a chopping to a grinding pattern, were observed after orthognathic treatment (closing angle P masticatory chewing pattern and muscle activity. However, the chewing pattern remains incomplete compared with controls. © 2015 John Wiley & Sons Ltd.

  12. The impact of HLA class I and EBV latency‐II antigen‐specific CD8+ T cells on the pathogenesis of EBV+ Hodgkin lymphoma

    Science.gov (United States)

    Jones, K.; Wockner, L.; Brennan, R. M.; Keane, C.; Chattopadhyay, P. K.; Roederer, M.; Price, D. A.; Cole, D. K.; Hassan, B.; Beck, K.; Gottlieb, D.; Ritchie, D. S.; Seymour, J. F.; Vari, F.; Crooks, P.; Burrows, S. R.

    2015-01-01

    Summary In 40% of cases of classical Hodgkin lymphoma (cHL), Epstein–Barr virus (EBV) latency‐II antigens [EBV nuclear antigen 1 (EBNA1)/latent membrane protein (LMP)1/LMP2A] are present (EBV+cHL) in the malignant cells and antigen presentation is intact. Previous studies have shown consistently that HLA‐A*02 is protective in EBV+cHL, yet its role in disease pathogenesis is unknown. To explore the basis for this observation, gene expression was assessed in 33 cHL nodes. Interestingly, CD8 and LMP2A expression were correlated strongly and, for a given LMP2A level, CD8 was elevated markedly in HLA‐A*02– versus HLA‐A*02+ EBV+cHL patients, suggesting that LMP2A‐specific CD8+ T cell anti‐tumoral immunity may be relatively ineffective in HLA‐A*02– EBV+cHL. To ascertain the impact of HLA class I on EBV latency antigen‐specific immunodominance, we used a stepwise functional T cell approach. In newly diagnosed EBV+cHL, the magnitude of ex‐vivo LMP1/2A‐specific CD8+ T cell responses was elevated in HLA‐A*02+ patients. Furthermore, in a controlled in‐vitro assay, LMP2A‐specific CD8+ T cells from healthy HLA‐A*02 heterozygotes expanded to a greater extent with HLA‐A*02‐restricted compared to non‐HLA‐A*02‐restricted cell lines. In an extensive analysis of HLA class I‐restricted immunity, immunodominant EBNA3A/3B/3C‐specific CD8+ T cell responses were stimulated by numerous HLA class I molecules, whereas the subdominant LMP1/2A‐specific responses were confined largely to HLA‐A*02. Our results demonstrate that HLA‐A*02 mediates a modest, but none the less stronger, EBV‐specific CD8+ T cell response than non‐HLA‐A*02 alleles, an effect confined to EBV latency‐II antigens. Thus, the protective effect of HLA‐A*02 against EBV+cHL is not a surrogate association, but reflects the impact of HLA class I on EBV latency‐II antigen‐specific CD8+ T cell hierarchies. PMID:26422112

  13. 40 CFR 147.51 - State-administered program-Class I, III, IV, and V wells.

    Science.gov (United States)

    2010-07-01

    ... PROGRAMS Alabama § 147.51 State-administered program—Class I, III, IV, and V wells. The UIC program for Class I, III, IV and V wells in the State of Alabama, except those on Indian lands, is the program... for Class I, III, IV, and V UIC Program,” September 21, 1982; (3) Letter from Alabama Chief Assistant...

  14. 40 CFR 147.251 - EPA-administered program-Class I, III, IV and V wells and Indian lands.

    Science.gov (United States)

    2010-07-01

    ... INJECTION CONTROL PROGRAMS California § 147.251 EPA-administered program—Class I, III, IV and V wells and Indian lands. (a) Contents. The UIC program in the State of California for Class I, III, IV and V wells... 40 Protection of Environment 22 2010-07-01 2010-07-01 false EPA-administered program-Class I, III...

  15. 40 CFR 147.301 - EPA-administered program-Class I, III, IV, V wells and Indian lands.

    Science.gov (United States)

    2010-07-01

    ... INJECTION CONTROL PROGRAMS Colorado § 147.301 EPA-administered program—Class I, III, IV, V wells and Indian lands. (a) Contents. The UIC program for Class I, III, IV and V wells on all lands in Colorado... 40 Protection of Environment 22 2010-07-01 2010-07-01 false EPA-administered program-Class I, III...

  16. Má oclusão Classe III de Angle com discrepância ântero-posterior acentuada Angle Class III malocclusion with severe anteroposterior disharmony

    Directory of Open Access Journals (Sweden)

    Marcos Alan Vieira Bittencourt

    2009-02-01

    Full Text Available A má oclusão Classe III de Angle é caracterizada por uma discrepância dentária ântero-posterior, que pode ou não estar acompanhada por alterações esqueléticas. Em geral, o aspecto facial fica bastante comprometido, sendo justamente esse fator, na maioria das vezes, que motiva o paciente a procurar pelo tratamento. Este caso foi apresentado à Diretoria do Board Brasileiro de Ortodontia e Ortopedia Facial (BBO, representando a categoria 4, ou seja, uma má oclusão com discrepância ântero-posterior acentuada, Classe III, com ANB menor ou igual a -2º, como parte dos requisitos para a obtenção do título de Diplomado pelo BBO.Angle Class III malocclusion is characterized by an anteroposterior dental discrepancy which may or may not be accompanied by skeletal changes. In general, distressed by a significantly compromised facial aspect, patients tend to seek treatment. This case was presented to the Brazilian Board of Orthodontics and Facial Orthopedics (BBO, as representative of Category 4, i.e., a malocclusion with severe anteroposterior discrepancy, Class III, and ANB Angle equal to or smaller than -2º, as part of the requirements for obtaining the BBO Diploma.

  17. Maxillary Transverse Comparison of Skeletal Class I and Class III Patient Populations Using Cone Beam Computed Tomography

    Science.gov (United States)

    2012-04-13

    image. Establishing diagnostic problems in this plane can be critical even in the youngest of patients as cessation of the transverse growth comes...Williams CE. Control of the transverse dimension with surgery and orthodontics . Am J Orthod 1980;77:284-306 (NEED) 62     23. Lagravere MO...i     MAXILLARY TRANSVERSE COMPARISON OF SKELETAL CLASS I AND CLASS III PATIENT POPULATIONS USING CONE BEAM COMPUTED TOMOGRAPHY A

  18. Morphometric Analysis of the Mandible in Subjects with Class III Malocclusion

    OpenAIRE

    Jin-Yun Pan; Szu-Ting Chou; Hong-Po Chang; Pao-Hsin Liu

    2006-01-01

    This study evaluated the deformations that contribute to Class III mandibular configuration, employing geometric morphometric analysis. Lateral cephalograms of male and female groups of 100 young adults and 70 children with Class III malocclusion were compared to those of counterparts with normal occlusion. The sample included an equal number of both genders. The cephalographs were traced, and 12 homologous landmarks were identified and digitized. Average mandibular geometries were generated ...

  19. Orthosurgical management of an asymmetric case with class III malocclusion and transversal problem in the maxilla

    OpenAIRE

    Juan Carlos Perez Varela; Beatriz Iglesias Sanchez

    2016-01-01

    Class III malocclusions are considered to be one of the most difficult problems to treat. For us, the complex of these cases is the esthetic of the face and the smile because the treatment of the malocclusions without surgery produces a more retrusive face. We present a case report of an adult male patient with skeletal Class III malocclusion with compression in the maxilla and mandibular asymmetry, who has treated the orthosurgical approach. The result is acceptable in terms of occlusion-fun...

  20. Camouflage treatment of skeletal Class III malocclusion with conventional orthodontic therapy.

    Science.gov (United States)

    Park, Jae Hyun; Yu, Joseph; Bullen, Ryan

    2017-04-01

    Nonextraction camouflage treatment along with Class III elastics was used to treat a 39-year-old woman with a skeletal Class III pattern and a low mandibular plane angle and short lower anterior facial height. The total active treatment time was 26 months. Her occlusion, smile esthetics, and soft tissue profile were significantly improved after treatment. Copyright © 2017 American Association of Orthodontists. Published by Elsevier Inc. All rights reserved.

  1. Combination of expansion and orthognathic surgery in a severe hyperdivergent skeletal Class III malocclusion

    Directory of Open Access Journals (Sweden)

    Anadha Gujar

    2016-01-01

    Full Text Available Class III malocclusions with a severe hyperdivergent growth pattern are very complex to plan and treat. This case report describes the treatment of an adult with a skeletal Class III malocclusion with a midface deficiency, severe bilateral posterior crossbite, and a severe hyperdivergent growth pattern by a combination of a bonded rapid maxillary expansion appliance and surgical procedure of Le Fort I osteotomy for maxillary advancement.

  2. Prevalent HLA Class II Alleles in Mexico City Appear to Confer Resistance to the Development of Amebic Liver Abscess

    Science.gov (United States)

    Hernández, Eric G.; Granados, Julio; Partida-Rodríguez, Oswaldo; Valenzuela, Olivia; Rascón, Edgar; Magaña, Ulises; Escamilla-Tilch, Mónica; López-Reyes, Alberto; Nieves-Ramírez, Miriam; González, Enrique; Morán, Patricia; Rojas, Liliana; Valadez, Alicia; Luna, Alexandra; Estrada, Francisco J.; Maldonado, Carmen; Ximénez, Cecilia

    2015-01-01

    Amebiasis is an endemic disease and a public health problem throughout Mexico, although the incidence rates of amebic liver abscess (ALA) vary among the geographic regions of the country. Notably, incidence rates are high in the northwestern states (especially Sonora with a rate of 12.57/100,000 inhabitants) compared with the central region (Mexico City with a rate of 0.69/100,000 inhabitants). These data may be related to host genetic factors that are partially responsible for resistance or susceptibility. Therefore, we studied the association of the HLA-DRB1 and HLA-DQB1 alleles with resistance or susceptibility to ALA in two Mexican populations, one each from Mexico City and Sonora. Ninety ALA patients were clinically diagnosed by serology and sonography. Genomic DNA was extracted from peripheral blood mononuclear cells. To establish the genetic identity of both populations, 15 short tandem repeats (STRs) were analyzed with multiplexed PCR, and the allelic frequencies of HLA were studied by PCR-SSO using LUMINEX technology. The allele frequencies obtained were compared to an ethnically matched healthy control group (146 individuals). We observed that both affected populations differed genetically from the control group. We also found interesting trends in the population from Mexico City. HLA-DQB1*02 allele frequencies were higher in ALA patients compared to the control group (0.127 vs 0.047; p= 0.01; pc= NS; OR= 2.9, 95% CI= 1.09-8.3). The less frequent alleles in ALA patients were HLA-DRB1*08 (0.118 vs 0.238 in controls; p= 0.01; pc= NS; OR= 0.42, 95% CI= 0.19-0.87) and HLA-DQB1*04 (0.109 vs 0.214; p= 0.02; pc= NS; OR= 0.40, 95% CI= 0.20-0.94). The haplotype HLA-DRB1*08/-DQB1*04 also demonstrated a protective trend against the development of this disease (0.081 vs. 0.178; p=0.02; pc=NS; OR= 0.40, 95% CI= 0.16-0.93). These trends suggest that the prevalent alleles in the population of Mexico City may be associated with protection against the development of ALA

  3. Prevalent HLA Class II Alleles in Mexico City Appear to Confer Resistance to the Development of Amebic Liver Abscess.

    Directory of Open Access Journals (Sweden)

    Eric G Hernández

    Full Text Available Amebiasis is an endemic disease and a public health problem throughout Mexico, although the incidence rates of amebic liver abscess (ALA vary among the geographic regions of the country. Notably, incidence rates are high in the northwestern states (especially Sonora with a rate of 12.57/100,000 inhabitants compared with the central region (Mexico City with a rate of 0.69/100,000 inhabitants. These data may be related to host genetic factors that are partially responsible for resistance or susceptibility. Therefore, we studied the association of the HLA-DRB1 and HLA-DQB1 alleles with resistance or susceptibility to ALA in two Mexican populations, one each from Mexico City and Sonora. Ninety ALA patients were clinically diagnosed by serology and sonography. Genomic DNA was extracted from peripheral blood mononuclear cells. To establish the genetic identity of both populations, 15 short tandem repeats (STRs were analyzed with multiplexed PCR, and the allelic frequencies of HLA were studied by PCR-SSO using LUMINEX technology. The allele frequencies obtained were compared to an ethnically matched healthy control group (146 individuals. We observed that both affected populations differed genetically from the control group. We also found interesting trends in the population from Mexico City. HLA-DQB1*02 allele frequencies were higher in ALA patients compared to the control group (0.127 vs 0.047; p= 0.01; pc= NS; OR= 2.9, 95% CI= 1.09-8.3. The less frequent alleles in ALA patients were HLA-DRB1*08 (0.118 vs 0.238 in controls; p= 0.01; pc= NS; OR= 0.42, 95% CI= 0.19-0.87 and HLA-DQB1*04 (0.109 vs 0.214; p= 0.02; pc= NS; OR= 0.40, 95% CI= 0.20-0.94. The haplotype HLA-DRB1*08/-DQB1*04 also demonstrated a protective trend against the development of this disease (0.081 vs. 0.178; p=0.02; pc=NS; OR= 0.40, 95% CI= 0.16-0.93. These trends suggest that the prevalent alleles in the population of Mexico City may be associated with protection against the

  4. Articulación de fones en individuos clase esqueletal I,II y III Speech patterns in skeletal class I, II and III subjects

    Directory of Open Access Journals (Sweden)

    Pía Villanueva

    2009-09-01

    Full Text Available OBJETIVO: determinar los patrones de articulación de fones consonánticos en sujetos de habla española chilena clases I, II y III esqueletal; comparar las diferencias fonéticas que existan entre clases esqueletales. MÉTODOS: se seleccionaron 54 individuos que cumplían con los criterios de inclusión determinados mediante un examen clínico intraoral y a través del análisis de Ricketts, y se conformaron los grupos de estudio de pacientes clases esqueletales I, II y III. Se les realizó un examen fonoarticulatorio estandarizado para determinar los fones modificados y el patrón articulatorio compensatorio realizado. RESULTADOS: se observaron cambios en el punto de articulación de fones consonánticos en las tres clases esqueletales, con diferencias significativas en los grupos de fones anteriores y medios entre pacientes clases I y II, sólo en el grupo de los fones anteriores entre pacientes I y III. Entre pacientes clases II y III no se observaron diferencias significativas. Se reportan modificaciones y compensaciones cualitativamente distintas entre las clases esqueletales. CONCLUSIONES: en relación a pacientes clase I, los pacientes clase II o III, presentan distinto grado de modificación en el punto de articulación de fones consonánticos. Las diferencias observadas se relacionan con los patrones esqueletales propios de cada clase.PURPOSE: to determine the consonant phonemes articulation patterns in Chilean skeletal class I, II and III Spanish speakers and compare their phonetic differences. METHODS: fifty-four skeletal class I, II and III subjects were selected, based on intraoral clinical examination and Ricketts cephalometric analysis, constituting the study groups. A standardized phonoarticulatory test was applied to each patient to determine the modified phonemes and their compensatory patterns. RESULTS: the findings indicate changes in articulation in all three groups. Significant differences were found in anterior and medium

  5. Cephalometric Evaluation of Dentofacial Features of Class III Malocclusion in Adults of Mashhad, Iran

    Directory of Open Access Journals (Sweden)

    Maryam Pousti

    2007-12-01

    Full Text Available

    Background and aims. Class III malocclusions are considered as one of the most complex orthodontic problems to diagnose and treat. Numerous studies have been conducted to determine the morphologic characteristics of craniofacial complex in patients with this malocclusion. The aim of this study was to determine the dentofacial characteristics of Class III malocclusion in Mashhadian adults.

    Materials and Methods. This cross-sectional descriptive study consisted of 114 cephalograms including 57 individuals with Class III malocclusion (28 males and 29 females with mean age of 19.28 years as the case group, and 57 adults with uncrowded Class I occlusion (28 males and 29 females with mean age of 17.2 years as the control group. Cephalometric evaluation was performed by measuring nine angular and nine linear measurements and the dentofacial characteristics of two groups were compared by Student’s t-test.

    Results. SNA angle, the distance from A point to Nasion perpendicular and the maxillary effective length was significantly lower in Class III group, while SNB and SN-Pog angles were significantly higher compared to control group. Mandibular effective length did not differ in two groups. Maxillary incisor protrusion and mandibular incisor retrusion in Class III subjects was also observed. From the vertical aspect, only mandibular plane angle showed an increase in Class III group (P < 0.05.

    Conclusion. Maxillary deficiency, mandibular prognathism, maxillary incisors protrusion and mandibular incisors retrusion are present in individuals with Class III malocclusion, but mandibular effective length does not differ significantly from Class I patients.

  6. Morphometric Analysis of the Mandible in Subjects with Class III Malocclusion

    Directory of Open Access Journals (Sweden)

    Jin-Yun Pan

    2006-07-01

    Full Text Available This study evaluated the deformations that contribute to Class III mandibular configuration, employing geometric morphometric analysis. Lateral cephalograms of male and female groups of 100 young adults and 70 children with Class III malocclusion were compared to those of counterparts with normal occlusion. The sample included an equal number of both genders. The cephalographs were traced, and 12 homologous landmarks were identified and digitized. Average mandibular geometries were generated by means of Procrustes analysis. Thin-plate spline analysis was then applied to mandibular configurations to determine local form differences in male and female groups of adults and children with normal occlusion and Class III malocclusion. The mandibular morphology was significantly different between these two groups of male and female adults, and children (p < 0.0001. This spline analysis revealed an anteroposterior elongation of the mandible along the condylion-gnathion axis, showing an extension in the regions of the mandibular condyle and ramus, and of the anteroinferior portion of the mandibular symphysis in Class III groups. More extension was evident in Class III adults. The deformations in subjects with Class III malocclusion may represent a developmental elongation of the mandible anteroposteriorly, which leads to the appearance of a prognathic mandibular profile.

  7. Prosthodontic treatment of an Angle III Class malocclusion: A case report.

    Science.gov (United States)

    Kuliš, Andreja; Kopač, Igor

    2017-07-20

    Patients with an Angle Class III malocclusion are generally treated by orthodontics with or without orthognathic surgery. A literature search revealed very few articles describing solely the prosthodontic treatment of a Class III malocclusion, as it is rarely used as a treatment modality in these cases. The purpose of this article is to show the effects and benefits of an increase in the vertical dimension of the occlusion (VDO) in patients with a Class III malocclusion. An increase in the VDO causes a clockwise rotation of the mandible, thereby increasing the reverse overjet. This phenomenon allows a prosthodontic treatment of the Class III malocclusion in some patients. Therefore, proper diagnostic procedures, careful planning, and a simulation of the final appearance by wax-up and mock-up are mandatory when choosing the modality of prosthodontic treatment. A case with a Class III malocclusion, treated solely by prosthodontic means, is presented. The implemented prosthodontic treatment included the correction of the crossbite and the occlusal plane, the reestablishment of the anterior and canine guidance as well as the provision of a stable occlusion and enhanced facial and dental esthetics. It is proposed that an increase of the VDO should be taken into consideration whenever a patient with a Class III malocclusion is prosthodontically treated.

  8. Orthodontic-surgical treatment of the skeletal class III malocclusion: a case report.

    Science.gov (United States)

    Stojanović, Ljiljana S; Mileusnić, Ivan; Mileusnić, Budimir; Cutović, Tatjana

    2013-02-01

    Class III malocclusions are considered to be ones of the most difficult problems to treat. Their causes are multifactorial and include genetic and/or environmental factors. Class III malocclusions are generally classified into 2 categories: skeletal and dental. The diagnosis is important due to the different treatment approaches. Generally a dental class III can be treated with orthodontics alone, while a true skeletal class III requires a combination of orthodontics and surgery. We presented a female patient with skeletal Class III malocclusion. The treatment was complete with positive overbite and acceptable occlusion using a combination of fixed orthodontic appliance treatment as well as the surgical operation. The patient was happy with her new appearance and function. Class III discrepancy should be diagnosed and classified according to its etiology and treated with appropriate surgery, including, if necessary, not only mandibular, but also maxillary surgery, in order to achieve a normal facial appearance. In any case, as the field of orthodontics continues to develop technologically and philosophically, we can expect that advances in diagnosis and treatment planning are im minent and inevitable.

  9. Treatment Options for Class III Malocclusion in Growing Patients with Emphasis on Maxillary Protraction.

    Science.gov (United States)

    Azamian, Zeinab; Shirban, Farinaz

    2016-01-01

    It is very difficult to diagnose and treat Class III malocclusion. This type of malocclusion involves a number of cranial base and maxillary and mandibular skeletal and dental compensation components. In Class III malocclusion originating from mandibular prognathism, orthodontic treatment in growing patients is not a good choice and in most cases orthognathic surgery is recommended after the end of growth. Approximately 30-40% of Class III patients exhibit some degree of maxillary deficiency; therefore, devices can be used for maxillary protraction for orthodontic treatment in early mixed dentition. In cases in which dental components are primarily responsible for Class III malocclusion, early therapeutic intervention is recommended. An electronic search was conducted using the Medline database (Entrez PubMed), the Cochrane Collaboration Oral Health Group Database of Clinical Trials, Science Direct, and Scopus. In this review article, we described the treatment options for Class III malocclusion in growing patient with an emphasis on maxillary protraction. It seems that the most important factor for treatment of Class III malocclusion in growing patient is case selection.

  10. Effects of Class III malocclusion on young male adults' vocal tract development: a pilot study.

    Science.gov (United States)

    Xue, Steve An; Lam, Connie W-Y; Whitehill, Tara L; Samman, Nabil

    2011-03-01

    To compare the vocal tract configuration between male speakers with Class III malocclusion and their normally developing counterparts and to investigate the concomitant acoustic changes caused by the alterations in vocal tract configuration. Eight young male patients with Class III malocclusion and 8 normally developing counterparts participated in this study. Acoustic reflection technology was used to measure vocal tract dimensions in the 2 groups. A continuous speech sample and 4 sustained vowels (/a/, /æ/, /i/, and /u/) were recorded from each participant to obtain the fundamental frequency and the first 3 formant frequencies (F1, F2, and F3). The results showed significantly greater oral length and oral volume for young male patients with Class III malocclusion than their cohorts. The F1 of vowel /u/ was found to be significantly higher in male patients with Class III malocclusion than their cohorts. The vowel space of the 4 recorded vowels was reduced and the F1-F2 formant map for /u/ was relatively more scattered in male patients with Class III malocclusion than in the control speakers. This study has provided preliminary information on the effects of Class III malocclusion on vocal tract configuration and concomitant acoustic changes in young male patients. Copyright © 2011 American Association of Oral and Maxillofacial Surgeons. Published by Elsevier Inc. All rights reserved.

  11. Cephalometric assessment of maxillary length in Serbian children with skeletal class III.

    Science.gov (United States)

    Stojanović, Zdenka; Nikolić, Predrag; Nikodijević, Angelina; Milić, Jasmina; Stojanović, Branislav

    2013-07-01

    Malocclusion of skeletal class III is a complex irregularity of sagittal inter-jaw relationship, which is due to irregularities of sagittal position of one or both of the jaw bones, which is often associated with disproportionate ratio of their length. The aim of this study was to determine whether the length of the jaw of children with skeletal class III in the period of mixed dentition was changed. Fifty children with skeletal class III and the same number of those with skeletal class I, of both sexes, have been selected on the basis of cephalometric analysis of profile tele-x-ray of the head. All the children aged 6-12 had mixed dentition, and were divided according to sex and age into three subgroups within each group. The length of maxilla, mandible and cranial base were measured. Proportions among the lengths measured within each group were found and difference significance in the measured lengths and their proportions among groups and subgroups were evaluated. The children with skeletal class III, compared with the findings in the control group, had significantly lower values of maxillary length, total maxillary length, as well as lower values of their lengths in proportion to lengths of the front or the total length of cranial base and in proportion to mandibular lengths (p children with skeletal class III have significantly shorter maxilla than those with skeletal class I.

  12. Aloimunidade contra antígenos HLA de classe I em pacientes com síndromes mielodisplásicas e anemia aplástica Aloimmunity against HLA class I antigens in patients with myelodisplastic syndrome and aplastic anemia

    Directory of Open Access Journals (Sweden)

    Daisy M. M. Arruda

    2008-02-01

    Full Text Available As síndromes mielodisplásicas (SMD e a anemia aplástica (AA apresentam citopenias periféricas necessitando, com freqüência, de reposições transfusionais contínuas de concentrados de hemácias e/ou de concentrados de plaquetas. O objetivo do presente estudo foi verificar a ocorrência de anticorpos anti-HLA de classe I em pacientes portadores das SMD e AA atendidos no ambulatório de Hematologia do Hemoce/UFC. Foram analisados 110 pacientes, sendo 70 com SMD e 40 com AA. A pesquisa de anticorpos anti-HLA de classe I foi realizada frente a um painel (PRA, utilizando-se a técnica de microlinfocitotoxicidade dependente do complemento. Vinte (28,6% dos 70 pacientes com as SMD e 18 (45% dos 40 pacientes com AA desenvolveram anticorpos anti-HLA contra o PRA. Esses pacientes que receberam uma carga de antígenos estranhos advindos de múltiplas transfusões de vários doadores de CH e/ou CP, geralmente desenvolvem aloanticorpos contra os antígenos HLA presentes na superfície das plaquetas e dos leucócitos que contaminam esses concentrados. A produção desses anticorpos pode trazer sérias complicações para o tratamento dos pacientes com SMD e AA. As avaliações sistemáticas para detecção de anticorpos anti-HLA após a reposição transfusional podem ser valiosas para adoção de estratégias transfusionais mais adequadas para esta população de pacientes.Patients with myelodysplastic syndromes (MDS or aplastic anemia (AA present peripheral cytopenias and require continuous transfusions of red cell and/or platelet concentrates. The objective of this study is to verify the existence of anti-HLA class 1 antibodies in patients with MDS and AA treated at the hematology Out patient Clinic of Hemoce/UFC. A total of 110 patients were analyzed, 70 with MDS and 40 with AA. Anti-HLA class 1 antibody detection was achieved with an antibody reactivity panel using the complement-dependent microlymphocytotoxicity technique. A total of 20 (28.6% of

  13. Classification of human leukocyte antigen (HLA) supertypes

    DEFF Research Database (Denmark)

    Wang, Mingjun; Claesson, Mogens H

    2014-01-01

    , the barrier to the development of peptide-based vaccines with maximum population coverage is that the restricting HLA genes are extremely polymorphic resulting in a vast diversity of peptide-binding HLA specificities and a low population coverage for any given peptide-HLA specificity. One way to reduce......Identification of new antigenic peptides, derived from infectious agents or cancer cells, which bind to human leukocyte antigen (HLA) class I and II molecules, is of importance for the development of new effective vaccines capable of activating the cellular arm of the immune response. However...... this complexity is to group thousands of different HLA molecules into several so-called HLA supertypes: a classification that refers to a group of HLA alleles with largely overlapping peptide binding specificities. In this chapter, we focus on the state-of-the-art classification of HLA supertypes including HLA...

  14. Pressure from the lips and the tongue in children with class III malocclusion*

    Science.gov (United States)

    Ruan, Wen-hua; Su, Ji-mei; Ye, Xiao-wei

    2007-01-01

    Objective: To discuss possible relationships between class III malocclusion and perioral forces by measuring the pressure from the lips and the tongue of children with class III malocclusion. Methods: Thirty-one children with class III malocclusion were investigated and their perioral forces were measured at rest and during swallowing under natural head position by a custom-made miniperioral force computer measuring system. Results: The resting pressures exerted on the labial side and palatine side of the upper left incisor, as well as the labial side and lingual side of the lower left incisor, were 0 g/cm2, 0 g/cm2, 0.57 g/cm2 and 0.23 g/cm2, respectively. Correspondingly, the swallowing forces were 2.87 g/cm2, 5.97 g/cm2, 4.09 g/cm2 and 7.89 g/cm2, respectively. No statistical difference between muscular pressure and gender existed. During swallowing, the lingual forces were significantly higher than the labial forces (Pchildren with class III malocclusion had lower perioral forces. The upper labial resting forces (Pclass III malocclusion and normal occlusion. Conclusion: Patients with class III malocclusion have lower perioral forces and this muscle hypofunction may be secondary to the spatial relations of the jaws. The findings support the spatial matrix hypothesis. PMID:17542055

  15. Pressure from the lips and the tongue in children with class III malocclusion.

    Science.gov (United States)

    Ruan, Wen-hua; Su, Ji-mei; Ye, Xiao-wei

    2007-05-01

    To discuss possible relationships between class III malocclusion and perioral forces by measuring the pressure from the lips and the tongue of children with class III malocclusion. Thirty-one children with class III malocclusion were investigated and their perioral forces were measured at rest and during swallowing under natural head position by a custom-made miniperioral force computer measuring system. The resting pressures exerted on the labial side and palatine side of the upper left incisor, as well as the labial side and lingual side of the lower left incisor, were 0 g/cm(2), 0 g/cm(2), 0.57 g/cm(2) and 0.23 g/cm(2), respectively. Correspondingly, the swallowing forces were 2.87 g/cm(2), 5.97 g/cm(2), 4.09 g/cm(2) and 7.89 g/cm(2), respectively. No statistical difference between muscular pressure and gender existed. During swallowing, the lingual forces were significantly higher than the labial forces (Pchildren with class III malocclusion had lower perioral forces. The upper labial resting forces (Pclass III malocclusion and normal occlusion. Patients with class III malocclusion have lower perioral forces and this muscle hypofunction may be secondary to the spatial relations of the jaws. The findings support the spatial matrix hypothesis.

  16. HLA-G polymorphisms and HLA-G expression in sarcoidosis

    DEFF Research Database (Denmark)

    Hviid, TVF; Milman, N; Hylenius, S

    2006-01-01

    HLA-G expression was investigated by immunohistochemistry in granulomas from sarcoidosis patients, weak HLA-G expression was observed in only one patient. CONCLUSIONS: HLA-G alleles that include a 14-bp sequence polymorphism in exon 8 of the HLA-G gene are observed more often in sarcoidosis patients......BACKGROUND: The MHC class Ib molecule Human Leukocyte Antigen (HLA)-G may be important in induction and maintenance of immunological tolerance, and HLA-G expression may have a role in different cancers, in certain diseases with associations to HLA, and in organ transplantation. Sarcoidosis...... is a systemic granulomatous disease with unknown etiology but at the molecular level several studies have shown HLA associations. METHODS: In the present study, HLA-G alleles/polymorphisms were studied in sarcoidosis patients (n = 47) and controls (n = 129) by PCR techniques and HLA-G protein expression...

  17. Enhanced Recognition of HIV-1 Cryptic Epitopes Restricted by HLA Class I Alleles Associated With a Favorable Clinical Outcome.

    Science.gov (United States)

    Bansal, Anju; Mann, Tiffanie; Sterrett, Sarah; Peng, Binghao J; Bet, Anne; Carlson, Jonathan M; Goepfert, Paul A

    2015-09-01

    Cryptic epitopes (CEs) are peptides derived from the translation of 1 or more of the 5 alternative reading frames (ARFs; 2 sense and 3 antisense) of genes. Here, we compared response rates to HIV-1-specific CE predicted to be restricted by HLA-I alleles associated with protection against disease progression to those without any such association. Peptides (9mer to 11mer) were designed based on HLA-I-binding algorithms for B*27, B*57, or B*5801 (protective alleles) and HLA-B*5301 or B*5501 (nonprotective allele) in all 5 ARFs of the 9 HIV-1 encoded proteins. Peptides with >50% probability of being an epitope (n = 231) were tested for T-cell responses in an IFN-γ enzyme-linked immunosorbent spot (ELISpot) assay. Peripheral blood mononuclear cell samples from HIV-1 seronegative donors (n = 42) and HIV-1 seropositive patients with chronic clade B infections (n = 129) were used. Overall, 16%, 2%, and 2% of chronic HIV infected patients had CE responses by IFN-γ ELISpot in the protective, nonprotective, and seronegative groups, respectively (P = 0.009, Fischer exact test). Twenty novel CE-specific responses were mapped (median magnitude of 95 spot forming cells/10 peripheral blood mononuclear cells), and most were both antisense derived (90%) and represented ARFs of accessory proteins (55%). CE-specific CD8 T cells were multifunctional and proliferated when assessed by intracellular cytokine staining. CE responses were preferentially restricted by the protective HLA-I alleles in HIV-1 infection, suggesting that they may contribute to viral control in this group of patients.

  18. A radiographic study of temporomandibular joints in skeletal class III malocclusion

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Sung Eun; Kim, Kae Duk [Chosun University College of Medicine, Kwangju (Korea, Republic of)

    2003-06-15

    To investigate the differences between the position of the mandibular condyles in temporomandibular joints of patients presenting with normal occlusion and skeletal class III malocclusion. Forty-two subjects with normal occlusion and thirty-seven subjects exhibiting skeletal class III malocclusion prior to orthodontic treatment were included in the study. Transcranial radiographs of each subject were taken at centric occlusion and 1 inch mouth opening. The positional relationship between the mandibular condyles with articular fossae and articular eminences at two positional states were evaluated and analyzed statistically. The mandibular condyles of the skeletal class III malocclusion group were found to be located more anteriorly from the center of the articular fossae compared to the normal occlusion group in centric occlusion. The mandibular condyles of the skeletal Class III malocclusion group were located more superiorly from the middle of articular height than those of the normal occlusion group in centric occlusion. However, these differences were not statistically significant. At 1 inch mouth opening, the mandibular condyles of the skeletal class III malocclusion group were placed more posteriorly from the articular eminences than those of the normal occlusion group. The mean angle of the articular eminence posterior slope were 56.51 .deg. {+-} 6.29 .deg. in the normal occlusion group and 60.37 .deg. {+-} 6.26 .deg. in the skeletal Class III malocclusion group. The mandibular condyles of the skeletal Class III malocclusion group were placed more anteriorly at centric occlusion and more posteriorly at 1 inch mouth opening when compared with those of the normal occlusion group.

  19. The ability of panoramic radiographs to correlate transverse with sagittal dimensions in class III patients

    Directory of Open Access Journals (Sweden)

    Mohsen Shirazi

    2017-02-01

    Full Text Available Background and Aims: In the field of orthodontics, gaining comprehensive information around dento-skeletal complex is necessary to choose the best treatment plan for each patient. The aim of this study was to investigate the linear and angular parameters in panoramic radiographs to find a path to correlate transvers to sagittal dimensions. Materials and Methods: Total number of sixty two, 8-14 years old children who sought for orthodontic therapy were selected (32 skeletal Class III and 30 skeletal Class I. They were exposed to x-ray to obtain the panoramic and lateral views in a controlled condition. Various linear and angular parameters were measured after tracing the landmarks on the panoramic radiograph. Data were obtained and analyzed using T-test. The level of significance was set at 0.05 (P<0.05. Results: Linear parameters of Co-Co, Go-Go and PTM-PTM were significantly lower in class III patients than class I ones (P=0.04, 0.04, 0.02, respectively. The ramus width value was also lower in class III patients. Angular parameters of  Me˄ and N˄ also showed the same results (P<0.001. Go˄ angle was significantly lower in the class I than class III patients (P=0.002, 0.007. Conclusion: Some traceable linear and angular parameters were found in the panoramic radiographs which had the potential to correlate the transverse with sagittal dimension.

  20. The HLA Class II Allele DRB1*1501 Is Over-Represented in Patients with Idiopathic Pulmonary Fibrosis

    Science.gov (United States)

    Alawad, Ahmad Samer; Feghali-Bostwick, Carol A.; Noth, Imre; Nathan, Steven D.; Rosen, Glenn D.; Rosas, Ivan O.; Dacic, Sanja; Ocak, Iclal; Fuhrman, Carl R.; Cuenco, Karen T.; Smith, Mary A.; Jacobs, Susan S.; Zeevi, Adriana; Morel, Penelope A.; Pilewski, Joseph M.; Valentine, Vincent G.; Gibson, Kevin F.; Kaminski, Naftali; Sciurba, Frank C.; Zhang, Yingze; Duncan, Steven R.

    2011-01-01

    Background Idiopathic pulmonary fibrosis (IPF) is a progressive and medically refractory lung disease with a grim prognosis. Although the etiology of IPF remains perplexing, abnormal adaptive immune responses are evident in many afflicted patients. We hypothesized that perturbations of human leukocyte antigen (HLA) allele frequencies, which are often seen among patients with immunologic diseases, may also be present in IPF patients. Methods/Principal Findings HLA alleles were determined in subpopulations of IPF and normal subjects using molecular typing methods. HLA-DRB1*15 was over-represented in a discovery cohort of 79 Caucasian IPF subjects who had lung transplantations at the University of Pittsburgh (36.7%) compared to normal reference populations. These findings were prospectively replicated in a validation cohort of 196 additional IPF subjects from four other U.S. medical centers that included both ambulatory patients and lung transplantation recipients. High-resolution typing was used to further define specific HLA-DRB1*15 alleles. DRB1*1501 prevalence in IPF subjects was similar among the 143 ambulatory patients and 132 transplant recipients (31.5% and 34.8%, respectively, p = 0.55). The aggregate prevalence of DRB1*1501 in IPF patients was significantly greater than among 285 healthy controls (33.1% vs. 20.0%, respectively, OR 2.0; 95%CI 1.3–2.9, p = 0.0004). IPF patients with DRB1*1501 (n = 91) tended to have decreased diffusing capacities for carbon monoxide (DLCO) compared to the 184 disease subjects who lacked this allele (37.8±1.7% vs. 42.8±1.4%, p = 0.036). Conclusions/Significance DRB1*1501 is more prevalent among IPF patients than normal subjects, and may be associated with greater impairment of gas exchange. These data are novel evidence that immunogenetic processes can play a role in the susceptibility to and/or manifestations of IPF. Findings here of a disease association at the HLA-DR locus have broad pathogenic

  1. HLA-DM interactions with intermediates in HLA-DR maturation and a role for HLA-DM in stabilizing empty HLA-DR molecules.

    Science.gov (United States)

    Denzin, L K; Hammond, C; Cresswell, P

    1996-12-01

    Major histocompatibility complex (MHC) class II-positive cell lines which lack HLA-DM expression accumulate class II molecules associated with residual invariant (I) chain fragments (class II-associated invariant chain peptides [CLIP]). In vitro, HLA-DM catalyzes CLIP dissociation from class II-CLIP complexes, promoting binding of antigenic peptides. Here the physical interaction of HLA-DM with HLA-DR molecules was investigated. HLA-DM complexes with class II molecules were detectable transiently in cells, peaking at the time when the class II molecules entered the MHC class II compartment. HLA-DR alpha beta dimers newly released from I chain, and those associated with I chain fragments, were found to associate with HLA-DM in vivo. Mature, peptide-loaded DR molecules also associated at a low level. These same species, but not DR-I chain complexes, were also shown to bind to purified HLA-DM molecules in vitro. HLA-DM interaction was quantitatively superior with DR molecules isolated in association with CLIP. DM-DR complexes generated by incubating HLA-DM with purified DR alpha beta CLIP contained virtually no associated CLIP, suggesting that this superior interaction reflects a prolonged HLA-DM association with empty class II dimers after CLIP dissociation. Incubation of peptide-free alpha beta dimers in the presence of HLA-DM was found to prolong their ability to bind subsequently added antigenic peptides. Stabilization of empty class II molecules may be an important property of HLA-DM in facilitating antigen processing.

  2. High Frequency of Transmitted HIV-1 Gag HLA Class I-Driven Immune Escape Variants but Minimal Immune Selection over the First Year of Clade C Infection

    Science.gov (United States)

    Gounder, Kamini; Padayachi, Nagavelli; Mann, Jaclyn K.; Radebe, Mopo; Mokgoro, Mammekwa; van der Stok, Mary; Mkhize, Lungile; Mncube, Zenele; Jaggernath, Manjeetha; Reddy, Tarylee; Walker, Bruce D.; Ndung’u, Thumbi

    2015-01-01

    In chronic HIV infection, CD8+ T cell responses to Gag are associated with lower viral loads, but longitudinal studies of HLA-restricted CD8+ T cell-driven selection pressure in Gag from the time of acute infection are limited. In this study we examined Gag sequence evolution over the first year of infection in 22 patients identified prior to seroconversion. A total of 310 and 337 full-length Gag sequences from the earliest available samples (median = 14 days after infection [Fiebig stage I/II]) and at one-year post infection respectively were generated. Six of 22 (27%) individuals were infected with multiple variants. There was a trend towards early intra-patient viral sequence diversity correlating with viral load set point (p = 0.07, r = 0.39). At 14 days post infection, 59.7% of Gag CTL epitopes contained non-consensus polymorphisms and over half of these (35.3%) comprised of previously described CTL escape variants. Consensus and variant CTL epitope proportions were equally distributed irrespective of the selecting host HLA allele and most epitopes remained unchanged over 12 months post infection. These data suggest that intrapatient diversity during acute infection is an indicator of disease outcome. In this setting, there is a high rate of transmitted CTL escape variants and limited immune selection in Gag during the first year of infection. These data have relevance for vaccine strategies designed to elicit effective CD8+ T cell immune responses. PMID:25781986

  3. High frequency of transmitted HIV-1 Gag HLA class I-driven immune escape variants but minimal immune selection over the first year of clade C infection.

    Directory of Open Access Journals (Sweden)

    Kamini Gounder

    Full Text Available In chronic HIV infection, CD8+ T cell responses to Gag are associated with lower viral loads, but longitudinal studies of HLA-restricted CD8+ T cell-driven selection pressure in Gag from the time of acute infection are limited. In this study we examined Gag sequence evolution over the first year of infection in 22 patients identified prior to seroconversion. A total of 310 and 337 full-length Gag sequences from the earliest available samples (median = 14 days after infection [Fiebig stage I/II] and at one-year post infection respectively were generated. Six of 22 (27% individuals were infected with multiple variants. There was a trend towards early intra-patient viral sequence diversity correlating with viral load set point (p = 0.07, r = 0.39. At 14 days post infection, 59.7% of Gag CTL epitopes contained non-consensus polymorphisms and over half of these (35.3% comprised of previously described CTL escape variants. Consensus and variant CTL epitope proportions were equally distributed irrespective of the selecting host HLA allele and most epitopes remained unchanged over 12 months post infection. These data suggest that intrapatient diversity during acute infection is an indicator of disease outcome. In this setting, there is a high rate of transmitted CTL escape variants and limited immune selection in Gag during the first year of infection. These data have relevance for vaccine strategies designed to elicit effective CD8+ T cell immune responses.

  4. PTPN22 Trp620 explains the association of chromosome 1p13 with type 1 diabetes and shows a statistical interaction with HLA class II genotypes.

    Science.gov (United States)

    Smyth, Deborah J; Cooper, Jason D; Howson, Joanna M M; Walker, Neil M; Plagnol, Vincent; Stevens, Helen; Clayton, David G; Todd, John A

    2008-06-01

    The disease association of the common 1858C>T Arg620Trp (rs2476601) nonsynonymous single nucleotide polymorphism (SNP) of protein tyrosine phosphatase; nonreceptor type 22 (PTPN22) on chromosome 1p13 has been confirmed in type 1 diabetes and also in other autoimmune diseases, including rheumatoid arthritis and Graves' disease. Some studies have reported additional associated SNPs independent of rs2476601/Trp(620), suggesting that it may not be the sole causal variant in the region and that the relative risk of rs2476601/Trp(620) is greater in lower risk by HLA class II genotypes than in the highest risk class II risk category. We resequenced PTPN22 and used these and other data to provide >150 SNPs to evaluate the association of the PTPN22 gene and its flanking chromosome region with type 1 diabetes in a minimum of 2,000 case subjects and 2,400 control subjects. Due to linkage disequilibrium, we were unable to distinguish between rs2476601/Trp(620) (P = 2.11 x10(-87)) and rs6679677 (P = 3.21 x10(-87)), an intergenic SNP between the genes putative homeodomain transcription factor 1 and round spermatid basic protein 1. None of the previously reported disease-associated SNPs proved to be independent of rs2476601/Trp(620). We did not detect any interaction with age at diagnosis or sex. However, we found that rs2476601/Trp(620) has a higher relative risk in type 1 diabetic case subjects carrying lower risk HLA class II genotypes than in those carrying higher risk ones (P = 1.36 x 10(-4) in a test of interaction). In our datasets, there was no evidence for allelic heterogeneity at the PTPN22 locus in type 1 diabetes, indicating that the SNP rs2476601/Trp(620) remains the best candidate in this chromosome region in European populations. The heterogeneity of rs2476601/Trp(620) disease risk by HLA class II genotype is consistent with previous studies, and the joint effect of the two loci is still greater in the high-risk group.

  5. EDITORIAL HLA SYSTEM AND CANCER

    African Journals Online (AJOL)

    ability to recognise antigen in its native conformation,. T cells recognise antigen that has been processed by other cells and presented to their surfaces by MHC molecules. The MHC molecules themselves are receptors for peptide antigens. The HLA gene system is divided into two classes - class I and class Il. Those in class.

  6. Early treatment of Class III malocclusion with a tandem traction bow appliance

    Directory of Open Access Journals (Sweden)

    Sneha Basaveshwar Valgadde

    2016-01-01

    Full Text Available Since Class III malocclusion is progressive in nature, the facial growth of Class III malocclusion worsens with age. Class III malocclusion is associated with a deviation in the sagittal relationship of the maxilla and the mandible, characterized by a deficient maxilla, retrognathic mandible, or a combination of both. The early orthopedic treatment of Class III malocclusions, at the end of primary dentition or the beginning of mixed dentition, prior to growth spurt, allows the accomplishment of successful results, providing facial balance, modifying the maxillofacial growth and development, and in many instances, preventing a future surgical treatment by increasing the stability. Many treatment approaches can be found in the literature regarding orthopedic and orthodontic treatment of Class III malocclusion, including intra- and extra-oral appliances. The major problem with extraoral anchorage has been of patient compliance due to its physical appearance. The case report presents an intraoral modified tandem appliance for maxillary protraction that has been used clinically to achieve successful results without relying much on patient co-operation.

  7. A missense mutation in DUSP6 is associated with Class III malocclusion.

    Science.gov (United States)

    Nikopensius, T; Saag, M; Jagomägi, T; Annilo, T; Kals, M; Kivistik, P A; Milani, L; Metspalu, A

    2013-10-01

    Class III malocclusion is a common dentofacial phenotype with a variable prevalence according to ethnic background. The etiology of Class III malocclusion has been attributed mainly to interactions between susceptibility genes and environmental factors during the morphogenesis of the mandible and maxilla. Class III malocclusion shows familial recurrence, and family-based studies support a predominance of an autosomal-dominant mode of inheritance. We performed whole-exome sequencing on five siblings from an Estonian family affected by Class III malocclusion. We identified a rare heterozygous missense mutation, c.545C>T (p.Ser182Phe), in the DUSP6 gene, a likely causal variant. This variant co-segregated with the disease following an autosomal-dominant mode of inheritance with incomplete penetrance. Transcriptional activation of DUSP6 has been presumed to be regulated by FGF/FGFR and MAPK/ERK signaling during fundamental processes at early stages of skeletal development. Several candidate genes within a linkage region on chromosome 12q22-q23--harboring DUSP6--are implicated in the regulation of maxillary or mandibular growth. The current study reinforces that the 12q22-q23 region is biologically relevant to craniofacial development and may be genetically linked to the Class III malocclusion.

  8. The Effect of Chin-cup Therapy in Class III Malocclusion: A Systematic Review.

    Science.gov (United States)

    Mousoulea, Sophia; Tsolakis, Ioannis; Ferdianakis, Efstratios; Tsolakis, Apostolos I

    2016-01-01

    The treatment of Class III malocclusion has been challenging for orthodontists. Among a plethora of treatment modalities, the chin-cup is considered a traditional appliance for early orthopedic intervention. The present study aims to investigate the current scientific evidence regarding the effectiveness of chin-cup therapy in Class III malocclusion of prognathic growing patients. A systematic review of the literature was conducted using PubMed/Medline and the Cochrane Central Register of Controlled Trials from January 1954 to October 2015. Articles were selected based on established inclusion/ exclusion criteria. The search strategy resulted in 3285 articles.14 studies were selected for the final analysis. They were all CCTs, 13 of retrospective and 1 of prospective design. Methodological quality was evaluated by a risk of bias assessment, as suggested by the Cochrane Risk of Bias Assessment Tool for Non-Randomized Studies on Interventions. The reported evidence presented favorable short-term outcomes both in hard and soft tissues improving the Class III profile, as well as desirable dento-alveolar changes, positively affecting the Class III malocclusion. There is considerable agreement between studies that chin-cup therapy can be considered for the short-term treatment of growing patients with Class III malocclusion, as indicated by favorable changes both in the hard and soft tissues. The existence of considerable risk of bias in all selected studies and the unclear long-term effectiveness of chin-cup therapy highlight the need for further investigation to draw reliable conclusions.

  9. Implant-assisted removable partial denture: An approach to switch Kennedy Class I to Kennedy Class III.

    Science.gov (United States)

    Ramchandran, Arun; Agrawal, Kaushal Kishor; Chand, Pooran; Ramashanker; Singh, Raghuwar Dayal; Gupta, Anusar

    2016-01-01

    The Kennedy Class I and II distal extension situation poses a challenge to the prosthodontist as it inherently possesses a lack of stability, which may be attributed to the difference in compressibility of the mucosa and the periodontal ligament surrounding the distal-most abutment tooth. This results in a rotational tendency of the prosthesis around the line connecting its terminal abutments. Placement of osseointegrated dental implants in the posterior edentulous regions, distal to the terminal abutment provides improved vertical support to the distal extension removable partial denture, effectively converting its intraoral performance from a Kennedy Class I to a Class III situation, thereby resulting in improved stability of the prosthesis and consequently, enhanced patient satisfaction. This case report describes such an approach to the restoration of a Kennedy Class I partially edentulous situation.

  10. Implant-assisted removable partial denture: An approach to switch Kennedy Class I to Kennedy Class III

    Directory of Open Access Journals (Sweden)

    Arun Ramchandran

    2016-01-01

    Full Text Available The Kennedy Class I and II distal extension situation poses a challenge to the prosthodontist as it inherently possesses a lack of stability, which may be attributed to the difference in compressibility of the mucosa and the periodontal ligament surrounding the distal-most abutment tooth. This results in a rotational tendency of the prosthesis around the line connecting its terminal abutments. Placement of osseointegrated dental implants in the posterior edentulous regions, distal to the terminal abutment provides improved vertical support to the distal extension removable partial denture, effectively converting its intraoral performance from a Kennedy Class I to a Class III situation, thereby resulting in improved stability of the prosthesis and consequently, enhanced patient satisfaction. This case report describes such an approach to the restoration of a Kennedy Class I partially edentulous situation.

  11. HLA-DRB4 gene encoded HLA-DR53 specificity segregating with the HLA-DR7, -DQ9 haplotype: unusual association.

    Science.gov (United States)

    Lardy, N M; van der Horst, A R; van de Weerd, M J; de Waal, L P; Bontrop, R E

    1998-02-01

    HLA phenotyping of a leukemia patient of Caucasoid origin revealed the presence of the serological HLA-DR53 specificity. Comprehensive pedigree analysis demonstrated that the HLA-DR53 specificity segregated with the HLA-DR7, -DQ3 haplotype. High resolution PCR- SSP genotyping of the HLA class II genes revealed the presence of the HLA-DRB4*0101101 allele segregating together with the HLA-DRB1*0701, -DQA1*0201 and DQB1*03032 alleles. This finding is in contrast to known linkages in that thus far, the HLA-DR7, -DQ9 haplotype has only been described in association with the non-expressed HLA-DRB4*0103102N allele. The existence of this "novel" haplotype may be explained by a homologous recombinational event that occurred between the HLA-DR7, -DR53, -DQ2 and the HLA-DR7, -DQ9 haplotypes.

  12. HLA-A alleles differentially associate with severity to Plasmodium ...

    African Journals Online (AJOL)

    Human Leukocyte Antigen (HLA), particularly HLA-B and class II alleles have been differentially associated with disease outcomes in different populations following infection with the malaria Plasmodium falciparum. However, the effect of HLA-A on malaria infection and/or disease is not fully understood. Recently, HLA-A ...

  13. 40 CFR 147.2800 - State-administered program-Class I, II, III, IV, and V wells.

    Science.gov (United States)

    2010-07-01

    ... I, II, III, IV, and V wells. The UIC program for Class I, II, III, IV, and V wells in the... 40 Protection of Environment 22 2010-07-01 2010-07-01 false State-administered program-Class I, II, III, IV, and V wells. 147.2800 Section 147.2800 Protection of Environment ENVIRONMENTAL PROTECTION...

  14. Results of Expedicion Humana. II. Analysis of HLA class II alleles in three African American populations from Colombia using the PCR/SSOP: identification of a novel DQB1*02 (*0203) allele.

    Science.gov (United States)

    Trachtenberg, E A; Keyeux, G; Bernal, J; Noble, J A; Erlich, H A

    1996-09-01

    PCR/SSOP typing methods were used to analyze the HLA Class II DRB1, DQA1, DQB1 and DPB1 loci of samples from three African American populations of Colombia. Forty samples from the Cauca (Pacific), and twenty samples each from the Choco (North Pacific Coast) and the Providencia (Caribbean island) populations, were collected and the Class II loci analyzed under the auspices of the Expedicion Humana. Despite the limited number of samples analyzed, the African Colombian populations exhibit a very high degree of class II polymorphism. A great diversity of DRB1 alleles was found, with representatives from all serological classes, including 19 DRB1 alleles in the Providencia, 16 in the Cauca and 14 in the Choco groups. In addition, a novel DQB1*02 allele (*0203) was found in two individuals from the Cauca population of the Pacific Coast. The sequence of the DQB1*0203 allele, associated with DR3, differs from DQB1*0201 by only one nucleotide substitution (C-->A) in the second position of codon 57, resulting in an Ala to Asp change. The addition of DQB1*0203 brings the total number of DQB1 alleles identified to date to 26. HLA class II diversity is much greater in these African Colombian populations than that seen in nearby Amerindian populations. Analysis of regional Colombian African American HLA population genetics is discussed with respect to the Colombian Amerindian HLA genetics described in an accompanying paper.

  15. Ocular toxoplasmosis: susceptibility in respect to the genes encoding the KIR receptors and their HLA class I ligands

    Science.gov (United States)

    Ayo, Christiane Maria; Frederico, Fábio Batista; Siqueira, Rubens Camargo; Brandão de Mattos, Cinara de Cássia; Previato, Mariana; Barbosa, Amanda Pires; Murata, Fernando Henrique Antunes; Silveira-Carvalho, Aparecida Perpétuo; de Mattos, Luiz Carlos

    2016-01-01

    The objective of this study was to investigate the influence of the genes encoding the KIR receptors and their HLA ligands in the susceptibility of ocular toxoplasmosis. A total of 297 patients serologically-diagnosed with toxoplasmosis were selected and stratified according to the presence (n = 148) or absence (n = 149) of ocular scars/lesions due to toxoplasmosis. The group of patients with scars/lesions was further subdivided into two groups according to the type of ocular manifestation observed: primary (n = 120) or recurrent (n = 28). Genotyping was performed by PCR-SSOP. Statistical analyses were conducted using the Chi-square test, and odds ratio with a 95% confidence interval was also calculated to evaluate the risk association. The activating KIR3DS1 gene was associated with increased susceptibility for ocular toxoplasmosis. The activating KIR together with their HLA ligands (KIR3DS1-Bw4-80Ile and KIR2DS1+/C2++ KIR3DS1+/Bw4-80Ile+) were associated with increased susceptibility for ocular toxoplasmosis and its clinical manifestations. KIR-HLA inhibitory pairs -KIR2DL3/2DL3-C1/C1 and KIR2DL3/2DL3-C1- were associated with decreased susceptibility for ocular toxoplasmosis and its clinical forms, while the KIR3DS1−/KIR3DL1+/Bw4-80Ile+ combination was associated as a protective factor against the development of ocular toxoplasmosis and, in particular, against recurrent manifestations. Our data demonstrate that activating and inhibitory KIR genes may influence the development of ocular toxoplasmosis. PMID:27827450

  16. Glass ionomer cement as an occlusive barrier in Class III furcation defect

    Directory of Open Access Journals (Sweden)

    Rameshwari Singhal

    2011-01-01

    Full Text Available Predicting the prognosis of molars that have experienced furcation invasion, is often a frustrating experience to the dental clinician and disappointing report to the patient involved. Although multiple treatment modalities have been attempted to retain teeth with severe furcation invasion, clinical success has not been predictable. A case report involving the use of glass ionomer cement (GIC as an occlusive barrier in the management of Class III furcation defect involving mandibular first molar is presented. A literature review on the subject matter was conducted using Medline, Google search engines, and manual library search. GIC restoration of Class III furcation invasion gives a satisfactory result. Surgical and nonsurgical treatment options are available for the management of the condition. GIC as an occlusive barrier in Class III furcation invasion is an economical and less invasive treatment option. It also makes home care easy for the patient.

  17. Human Leukocyte Antigen (HLA Class I Down-Regulation by Human Immunodeficiency Virus Type 1 Negative Factor (HIV-1 Nef: What Might We Learn From Natural Sequence Variants?

    Directory of Open Access Journals (Sweden)

    Philip Mwimanzi

    2012-09-01

    Full Text Available HIV-1 causes a chronic infection in humans that is characterized by high plasma viremia, progressive loss of CD4+ T lymphocytes, and severe immunodeficiency resulting in opportunistic disease and AIDS. Viral persistence is mediated in part by the ability of the Nef protein to down-regulate HLA molecules on the infected cell surface, thereby allowing HIV-1 to evade recognition by antiviral CD8+ T lymphocytes. Extensive research has been conducted on Nef to determine protein domains that are required for its immune evasion activities and to identify critical cellular co-factors, and our mechanistic understanding of this process is becoming more complete. This review highlights our current knowledge of Nef-mediated HLA class I down-regulation and places this work in the context of naturally occurring sequence variation in this protein. We argue that efforts to fully understand the critical role of Nef for HIV-1 pathogenesis will require greater analysis of patient-derived sequences to elucidate subtle differences in immune evasion activity that may alter clinical outcome.

  18. Relationship among amiodarone, new class III antiarrhythmics, miscellaneous agents and acquired long QT syndrome.

    Science.gov (United States)

    Riera, Andrés Ricardo Pérez; Uchida, Augusto Hiroshi; Ferreira, Celso; Ferreira Filho, Celso; Schapachnik, Edgardo; Dubner, Sergio; Zhang, Li; Moffa, Paulo Jorge

    2008-01-01

    Class III drugs prolong the QT interval by blocking mainly the delayed rectifier rapid potassium outward current (IKr), with little effect on depolarization. This K(+) channel in encoded by the human ether-a-go-go-related gene (hERG). Inhibition of hERG potassium currents by class III antiarrhythmic drugs causes lengthening of cardiac action potential, which produces a beneficial antiarrhythmic effect. Excessive prolongation of the action potential may lead to acquired long QT syndrome, which is associated with a risk of "torsade de pointes". Class III agents can block all types of potassium channels: IKs, IKr, IKur and IK1. The main representing class III agent is amiodarone. It is the gold standard in the prevention of recurrence of atrial fibrillation. Although it is highly effective in treating many arrhythmias, large number of adverse effects limits its clinical use. Dronedarone is a synthetic amiodarone analogue, iodine-free compound, with fewer adverse effects, and shares amiodarone's multichannel blocking effects, inhibiting transmembrane Na+, IKs, IKur, IK1, and slow Ca(++)L-type calcium currents. The main new generation class III drugs are: dofetilide, dronedarone, azimilide, and ibutilide. Oral dofetilide did not increase mortality in patients with a recent myocardial infarction or congestive heart failure. It is an alternative for the pharmacological conversion of atrial fibrillation and flutter. Azimilide blocks both rapid and slow potassium channels components. Azimilide is not a methanesulfonanilide compound. Trecitilide, tedisamil, ersentilide, ambasilide, chromanol and sematilide are class III miscellaneous agents. Old mixed agents are sotalol and bretylium. The present article reviews the main trials accomplished with these drugs.

  19. Non Classical HLA Genes and Non-HLA Genes in a Population of Infants at Familial Risk of Atopy

    Directory of Open Access Journals (Sweden)

    A. De Silvestri

    2006-01-01

    Full Text Available Aim: We investigated on parental history and IgE serum level in 2588 consecutive newborns to individuate babies “at risk” of atopy at birth and we analysed the polymorphisms of class III region to evaluate the association with immunogenetic markers of HLA: C4A, C4B, LTA, RAGE and TNFA genes; we performed TNF and IgE receptor (FCERB1 physiologically related gene polymorphisms.

  20. 40 CFR 147.2550 - State-administered program-Class I, III, IV and V wells.

    Science.gov (United States)

    2010-07-01

    ... CONTROL PROGRAMS Wyoming § 147.2550 State-administered program—Class I, III, IV and V wells. The UIC program for Class I, III, IV and V wells in the State of Wyoming, except those on Indian lands is the... 40 Protection of Environment 22 2010-07-01 2010-07-01 false State-administered program-Class I...

  1. 40 CFR 147.500 - State-administered program-Class I, III, IV, and V wells.

    Science.gov (United States)

    2010-07-01

    ... CONTROL PROGRAMS Florida § 147.500 State-administered program—Class I, III, IV, and V wells. The UIC program for Class I, III, IV, and V wells in the State of Florida, except for those on Indian lands is... 40 Protection of Environment 22 2010-07-01 2010-07-01 false State-administered program-Class I...

  2. 40 CFR 147.1601 - State-administered program-Class I, III, IV and V wells.

    Science.gov (United States)

    2010-07-01

    ... CONTROL PROGRAMS New Mexico § 147.1601 State-administered program—Class I, III, IV and V wells. The UIC program for Class I, III, IV and V injection wells in the State of New Mexico, except for those on Indian... 40 Protection of Environment 22 2010-07-01 2010-07-01 false State-administered program-Class I...

  3. 40 CFR 147.2250 - State-administered program-Class I, III, IV, and V wells.

    Science.gov (United States)

    2010-07-01

    ... CONTROL PROGRAMS Utah § 147.2250 State-administered program—Class I, III, IV, and V wells. The UIC program for Class I, III, IV, and V wells in the State of Utah, except those on Indian lands, is administered... 40 Protection of Environment 22 2010-07-01 2010-07-01 false State-administered program-Class I...

  4. 40 CFR 147.1301 - State-administered program-Class I, III, IV, and V wells.

    Science.gov (United States)

    2010-07-01

    ... CONTROL PROGRAMS Missouri § 147.1301 State-administered program—Class I, III, IV, and V wells. The UIC program for Class I, III, IV, and V wells in the State of Missouri, other than those on Indian lands, is... 40 Protection of Environment 22 2010-07-01 2010-07-01 false State-administered program-Class I...

  5. 40 CFR 147.1850 - State-administered program-Class I, III, IV and V wells.

    Science.gov (United States)

    2010-07-01

    ... CONTROL PROGRAMS Oklahoma § 147.1850 State-administered program—Class I, III, IV and V wells. The UIC program for Class I, III, IV, and V wells in the State of Oklahoma, except those on Indian lands, is the... 40 Protection of Environment 22 2010-07-01 2010-07-01 false State-administered program-Class I...

  6. 40 CFR 147.1751 - State-administered program-Class I, III, IV and V wells.

    Science.gov (United States)

    2010-07-01

    ... CONTROL PROGRAMS North Dakota § 147.1751 State-administered program—Class I, III, IV and V wells. The UIC program for Class I, III, IV, and V wells in the State of North Dakota, except those on Indian lands, is... 40 Protection of Environment 22 2010-07-01 2010-07-01 false State-administered program-Class I...

  7. 40 CFR 147.200 - State-administered program-Class I, III, IV, and V wells.

    Science.gov (United States)

    2010-07-01

    ... CONTROL PROGRAMS Arkansas § 147.200 State-administered program—Class I, III, IV, and V wells. The UIC program for Class I, III, IV and V wells in the State of Arkansas, except those wells on Indian lands, is... 40 Protection of Environment 22 2010-07-01 2010-07-01 false State-administered program-Class I...

  8. 40 CFR 147.700 - State-administered program-Class I, III, IV, and V wells.

    Science.gov (United States)

    2010-07-01

    ... CONTROL PROGRAMS Illinois § 147.700 State-administered program—Class I, III, IV, and V wells. The UIC program for Class I, III, IV and V wells in the State of Illinois, except those on Indian lands, is the... 40 Protection of Environment 22 2010-07-01 2010-07-01 false State-administered program-Class I...

  9. 40 CFR 147.1250 - State-administered program-Class I, III, IV, and V wells.

    Science.gov (United States)

    2010-07-01

    ... CONTROL PROGRAMS Mississippi § 147.1250 State-administered program—Class I, III, IV, and V wells. The UIC program for Class I, III, IV and V wells in the State of Mississippi, except those on Indian lands, is the... 40 Protection of Environment 22 2010-07-01 2010-07-01 false State-administered program-Class I...

  10. Orthosurgical management of an asymmetric case with class III malocclusion and transversal problem in the maxilla

    Directory of Open Access Journals (Sweden)

    Juan Carlos Perez Varela

    2016-01-01

    Full Text Available Class III malocclusions are considered to be one of the most difficult problems to treat. For us, the complex of these cases is the esthetic of the face and the smile because the treatment of the malocclusions without surgery produces a more retrusive face. We present a case report of an adult male patient with skeletal Class III malocclusion with compression in the maxilla and mandibular asymmetry, who has treated the orthosurgical approach. The result is acceptable in terms of occlusion-function, esthetic of the smile, and facial esthetics.

  11. Cephalometric assessment of maxillary length in Serbian children with skeletal class III

    Directory of Open Access Journals (Sweden)

    Stojanović Zdenka

    2013-01-01

    Full Text Available Background/Aim. Malocclusion of skeletal class III is a complex irregularity of sagittal inter-jaw relationship, which is due to irregularities of sagittal position of one or both of the jaw bones, which is often associated with disproportionate ratio of their length. The aim of this study was to determine whether the length of the jaw of children with skeletal class III in the period of mixed dentition was changed. Methods. Fifty children with skeletal class III and the same number of those with skeletal class I, of both sexes, have been selected on the basis of cephalometric analysis of profile tele-x-ray of the head. All the children aged 6-12 had mixed dentition, and were divided according to sex and age into three subgroups within each group. The length of maxilla, mandible and cranial base were measured. Proportions among the lengths measured within each group were found and difference significance in the measured lengths and their proportions among groups and subgroups were evaluated. Results. The children with skeletal class III, compared with the findings in the control group, had significantly lower values of maxillary length, total maxillary length, as well as lower values of their lengths in proportion to lengths of the front or the total length of cranial base and in proportion to mandibular lengths (p < 0.05. Among the patients of different sexes, both in the test and the control group, a significant difference in the values of the measured lengths was found. Conclusion. The children with skeletal class III have significantly shorter maxilla than those with skeletal class I.

  12. Phenotypic Diversity in Caucasian Adults with Moderate to Severe Class III Malocclusion

    Science.gov (United States)

    Moreno Uribe, Lina M.; Vela, Kaci C.; Kummet, Colleen; Dawson, Deborah V.; Southard, Thomas E.

    2014-01-01

    INTRODUCTION Class III malocclusion is characterized by a composite of dento-skeletal patterns that lead to the forward positioning of the mandibular teeth in relation to the maxillary teeth and a concave profile. Environmental and genetic factors are associated with this condition, which affects 1% of the US population and imposes significant esthetic and functional burdens on affected individuals. The purpose of this study was to capture the phenotypic variation present in a large sample of white adults with Class III malocclusion by using multivariate reduction methods. METHODS Sixty-three lateral cephalometric variables were measured from pre-treatment records of 292 Class II Caucasian adults (126 males, 166 females; ages 16-57 years). Principal component analysis and cluster analysis were used to capture the phenotypic variation and identify the most homogeneous groups of individuals to reduce genetic heterogeneity. RESULTS Principal component analysis resulted in 6 principal components that accounted for 81.2% of the variation. The first three components represented variations in mandibular horizontal and vertical position, maxillary horizontal position, and mandibular incisor angulation, respectively. The cluster model identified 5 distinct subphenotypes of Class III malocclusion. CONCLUSIONS A spectrum of phenotypic definitions was obtained replicating results of previous studies and supporting the validity of these phenotypic measures in future research of genetic and environmental etiology of Class III malocclusion. PMID:23810043

  13. Phenotypic diversity in white adults with moderate to severe Class III malocclusion.

    Science.gov (United States)

    Moreno Uribe, Lina M; Vela, Kaci C; Kummet, Colleen; Dawson, Deborah V; Southard, Thomas E

    2013-07-01

    Class III malocclusion is characterized by a composite of dentoskeletal patterns that lead to the forward positioning of the mandibular teeth in relation to the maxillary teeth and a concave profile. Environmental and genetic factors are associated with this condition, which affects 1% of the population in the United States and imposes significant esthetic and functional burdens on affected persons. The purpose of this study was to capture the phenotypic variation in a large sample of white adults with Class III malocclusion using multivariate reduction methods. Sixty-three lateral cephalometric variables were measured from the pretreatment records of 292 white subjects with Class II malocclusion (126 male, 166 female; ages, 16-57 years). Principal component analysis and cluster analysis were used to capture the phenotypic variation and identify the most homogeneous groups of subjects to reduce genetic heterogeneity. Principal component analysis resulted in 6 principal components that accounted for 81.2% of the variation. The first 3 components represented variation in mandibular horizontal and vertical positions, maxillary horizontal position, and mandibular incisor angulation. The cluster model identified 5 distinct subphenotypes of Class III malocclusion. A spectrum of phenotypic definitions was obtained replicating results of previous studies and supporting the validity of these phenotypic measures in future research of the genetic and environmental etiologies of Class III malocclusion. Copyright © 2013 American Association of Orthodontists. Published by Mosby, Inc. All rights reserved.

  14. Constitutive intracellular expression of human leukocyte antigen (HLA)-DO and HLA-DR but not HLA-DM in trophoblast cells.

    Science.gov (United States)

    Ranella, Anthi; Vassiliadis, Simon; Mastora, Chrisa; Valentina, Michailidou; Dionyssopoulou, Eva; Athanassakis, Irene

    2005-01-01

    The nonclassic human leukocyte antigen (HLA)-DM molecules have been proved to positively regulate antigen presentation in classic antigen-presenting cells, whereas in B lymphocytes HLA-DO have been identified as negative regulators of the process. The present report examines whether the negative expression of classic class II molecules in trophoblasts implies negative regulation by HLA-DO. It was revealed by immunofluorescence, confocal microscopy, and subcellular fractionation techniques that human trophoblasts, although not expressing any surface HLA-DR antigens, constitutively express intracellular HLA-DR, HLA-DO, and CD74, but not HLA-DM. Administration of interferon-gamma to the cell culture increased HLA-DR and CD74, induced HLA-DM, but did not alter the expression of HLA-DO and induced HLA-DR release from the cells. These results were confirmed by reverse transcriptase-polymerase chain reaction analysis except that HLA-DM mRNA was detected in control cells, indicating a posttranscriptional regulation. Under the same experimental conditions, human monocytes/macrophages were not expressing intracellular HLA-DO while exhibiting significant levels of HLA-DR, HLA-DM, and CD74. The results presented here reveal for the first time expression of HLA-DO in trophoblasts, which can be of great importance in maintaining the class II-negative state in these cells and consequently protecting the fetus from maternal immune attack.

  15. Management of skeletal Class III malocclusion with face mask therapy and comprehensive orthodontic treatment

    Directory of Open Access Journals (Sweden)

    Kirthika Muthukumar

    2016-01-01

    Full Text Available Orthopedic correction of skeletal Class III malocclusion in a growing patient is crucial as it can circumvent future surgical procedures. Further, as surgery is done only at a later stage, early treatment helps to avoid the detrimental effects produced by the facial disfigurement on the patient's social life. This case report describes the treatment of a child aged 9 years 6 months who had a skeletal Class III malocclusion. The treatment plan involved the use of a reverse pull headgear (facemask and multibracket appliance therapy resulting in successful correction of the malocclusion. The treatment results were highly satisfactory resulting in improved facial esthetics, a skeletal Class I with a Dental Class I molar and canine relationship, an ideal overjet and overbite. Thus, dentoalveolar camouflage, if done in properly selected cases, alleviates the need for surgical intervention. The patient is being monitored until the end of growth to ensure the stability of treatment results.

  16. Management of skeletal Class III malocclusion with face mask therapy and comprehensive orthodontic treatment.

    Science.gov (United States)

    Muthukumar, Kirthika; Vijaykumar, N M; Sainath, M C

    2016-01-01

    Orthopedic correction of skeletal Class III malocclusion in a growing patient is crucial as it can circumvent future surgical procedures. Further, as surgery is done only at a later stage, early treatment helps to avoid the detrimental effects produced by the facial disfigurement on the patient's social life. This case report describes the treatment of a child aged 9 years 6 months who had a skeletal Class III malocclusion. The treatment plan involved the use of a reverse pull headgear (facemask) and multibracket appliance therapy resulting in successful correction of the malocclusion. The treatment results were highly satisfactory resulting in improved facial esthetics, a skeletal Class I with a Dental Class I molar and canine relationship, an ideal overjet and overbite. Thus, dentoalveolar camouflage, if done in properly selected cases, alleviates the need for surgical intervention. The patient is being monitored until the end of growth to ensure the stability of treatment results.

  17. Long-term skeletal and profile stability after surgical-orthodontic treatment of Class II and Class III malocclusion.

    Science.gov (United States)

    de Lir, Ana de Lourdes Sá; de Moura, Walter Leal; Oliveira Ruellas, Antonio Carlos; Gomes Souza, Margareth Maria; Nojima, Lincoln Issamu

    2013-06-01

    The purpose of this perspective research was to study the long-term stability of skeletal, dentoalveolar and soft tissue after orthognathic surgery in subjects presenting with Class II and Class III malocclusions. The available digitized cephalometric radiographs, including pretreatment (t0), presurgery (t1), a minimum of 12 months postsurgery (t2) and at least 3 years after the orthosurgery treatment (t3) were taken between 1998 and 2010. In Group 1 mandibular advancement and in Group 2 mandibular advancement and maxillary impaction surgery were performed for correction of Class II. In Group 3 maxillary advancement and in Group 4 surgical maxillary advancement with mandibular setback, for correction of Class III. In all the phases mandibular length was shorter in Group 1, and the inferior third of the face was longer in Group 2. Before the surgery there was greater maxillary deficiency in Group 3 than Group 4 and mandibular length was longer in Group 4. In Groups 1 and 2, at retention phase, relapse occurred due to the increase in mandibular plane, whereas the surgeries performed in Groups 3 and 4 remained stable. Copyright © 2012 European Association for Cranio-Maxillo-Facial Surgery. Published by Elsevier Ltd. All rights reserved.

  18. HLA-DM and HLA-DO, key regulators of MHC-II processing and presentation.

    Science.gov (United States)

    Mellins, Elizabeth D; Stern, Lawrence J

    2014-02-01

    Peptide loading of class II MHC molecules in endosomal compartments is regulated by HLA-DM. HLA-DO modulates HLA-DM function, with consequences for the spectrum of MHC-bound epitopes presented at the cell surface for interaction with T cells. Here, we summarize and discuss recent progress in investigating the molecular mechanisms of action of HLA-DM and HLA-DO and in understanding their roles in immune responses. Key findings are the long-awaited structures of HLA-DM in complex with its class II substrate and with HLA-DO, and observation of a novel phenotype--autoimmunity combined with immunodeficiency--in mice lacking HLA-DO. We also highlight several areas where gaps persist in our knowledge about this pair of proteins and their molecular biology and immunobiology. Copyright © 2013 The Authors. Published by Elsevier Ltd.. All rights reserved.

  19. Association between HLA-A, HLA-C and HLA-B Genes and Ankylosing Spondylitis in Macedonian Population

    OpenAIRE

    Kirijas, Meri; Mishevska-Perchinkova, Snezhana; Karadzova-Stojanoska, Anzelika; Efinska-Mladenovska, Olivija; Petlichkovski, Aleksandar; Trajkov, Dejan; Spiroski, Mirko

    2014-01-01

    Aim: The aim of this study was to determine the association of HLA-A, -C and -B genes with ankylosing spondylitis in patients from the Republic of Macedonia.Material and Methods: This study included 307 subjects (250 healthy individuals and 57 patients with ankylosing spondylitis who were diagnosed at the University Clinic of Rheumatology in Skopje). The HLA typing of class 1 (HLA-A, HLA-C and HLA-B) genes was performed using the method of Reverse Line Strip, after isolation of DNK from the b...

  20. In silico calculated affinity of FVIII-derived peptides for HLA class II alleles predicts inhibitor development in haemophilia A patients with missense mutations in the F8 gene.

    Science.gov (United States)

    Pashov, A D; Calvez, T; Gilardin, L; Maillère, B; Repessé, Y; Oldenburg, J; Pavlova, A; Kaveri, S V; Lacroix-Desmazes, S

    2014-03-01

    Forty per cent of haemophilia A (HA) patients have missense mutations in the F8 gene. Yet, all patients with identical mutations are not at the same risk of developing factor VIII (FVIII) inhibitors. In severe HA patients, human leucocyte antigen (HLA) haplotype was identified as a risk factor for onset of FVIII inhibitors. We hypothesized that missense mutations in endogenous FVIII alter the affinity of the mutated peptides for HLA class II, thus skewing FVIII-specific T-cell tolerance and increasing the risk that the corresponding wild-type FVIII-derived peptides induce an anti-FVIII immune response during replacement therapy. Here, we investigated whether affinity for HLA class II of wild-type FVIII-derived peptides that correspond to missense mutations described in the Haemophilia A Mutation, Structure, Test and Resource database is associated with inhibitor development. We predicted the mean affinity for 10 major HLA class II alleles of wild-type FVIII-derived peptides that corresponded to 1456 reported cases of missense mutations. Linear regression analysis confirmed a significant association between the predicted mean peptide affinity and the mutation inhibitory status (P = 0.006). Significance was lost after adjustment on mutation position on FVIII domains. Although analysis of the A1-A2-A3-C1 domains yielded a positive correlation between predicted HLA-binding affinity and inhibitory status (OR = 0.29 [95% CI: 0.14-0.60] for the high affinity tertile, P = 0.002), the C2 domain-restricted analysis indicated an inverse correlation (OR = 3.56 [1.10-11.52], P = 0.03). Our data validate the importance of the affinity of FVIII peptides for HLA alleles to the immunogenicity of therapeutic FVIII in patients with missense mutations. © 2013 John Wiley & Sons Ltd.

  1. Effectiveness of interceptive treatment of class III malocclusions with skeletal anchorage: A systematic review and meta-analysis

    National Research Council Canada - National Science Library

    Jorge Rodríguez de Guzmán-Barrera; Carla Sáez Martínez; Montserrat Boronat-Catalá; Jose María Montiel-Company; Vanessa Paredes-Gallardo; José Luís Gandía-Franco; José Manuel Almerich-Silla; Carlos Bellot-Arcís

    2017-01-01

      Recently, new strategies for treating class III malocclusions have appeared. Skeletal anchorage appears to reduce the dentoalveolar effects while maximising the orthopaedic effect in growing patients...

  2. 76 FR 43701 - Renewal of Agency Information Collection for Class III Tribal State Gaming Compact Process...

    Science.gov (United States)

    2011-07-21

    ... Bureau of Indian Affairs Renewal of Agency Information Collection for Class III Tribal State Gaming Compact Process; Request for Comments AGENCIES: Bureau of Indian Affairs, Interior. ACTION: Notice of... Indian Affairs (BIA) is seeking comments on renewal of Office of Management and Budget (OMB) approval for...

  3. Adult Class III treatment using a J-hook headgear to the mandibular arch.

    Science.gov (United States)

    Kuroda, Yasuko; Kuroda, Shingo; Alexander, Richard G; Tanaka, Eiji

    2010-03-01

    To evaluate the treatment effects of high-pull J-hook headgear on the lower dental arch in nongrowing Class III patients. Fourteen nongrowing Class III patients having an Angle Class III malocclusion and ANB angle of less than 1.0 degree, were treated with high-pull J-hook headgear to the lower arch. Using lateral cephalograms and plaster models obtained before treatment (T1), after active treatment (T2), and after the retention period (T3), the treatment outcome was analyzed. The incisal edge of the lower central incisor moved a mean of 1.2 mm to the lingual and 1.7 mm to the occlusal between T1 and T2. The axis of the lower incisor inclined 4.0 degrees to the lingual. The lower first molar cusp moved 1.5 mm to the distal and the root apex moved 2.0 mm to the mesial. Molar angulations were tipped 9.8 degrees to the distal. The occlusal plane showed 4.5 degrees counterclockwise rotation. The mean intermolar width increased 1.5 mm on average. Comparison of the records between T2 and T3 showed minimal changes. Distal movement of the lower dental arch using J-hook headgear was clearly demonstrated, confirming that the application of high-pull J-hook headgear to the lower arch was effective for improvement of the Class III occlusion.

  4. Angle Class III malocclusion with anteroposterior and vertical discrepancy in the final stage of growth

    Directory of Open Access Journals (Sweden)

    Marcelo B. P de Arruda

    Full Text Available ABSTRACT Angle Class III malocclusion is characterized by an anteroposterior dental discrepancy with or without anteroposterior and vertical skeletal changes. Patients usually seek orthodontic treatment because facial appearance is compromised in most cases. The present study describes the clinical case of a 12-year and 6-month-old girl in her final stage of pubertal growth presenting Class III malocclusion with anteroposterior and vertical discrepancies. Initial treatment consisted of maxillary expansion using a Hass expander followed by the use of a Petit facemask for a minimum of 16 hours a day. During corrective treatment, Class III elastics were used to complement protraction. At the end of the treatment, skeletal discrepancy had improved, and the ANB angle increased from 0 to 2o. Angle Class III malocclusion, anterior crossbite and open bite were corrected. This case was presented to the Committee of the Brazilian Board of Orthodontics and Facial Orthopedics (BBO as part of the requisites to become a BBO Diplomate.

  5. Soft Tissue Characteristics and Gender Dimorphism in Class III Malocclusion: a Cephalometric Study in Adult Greeks

    Directory of Open Access Journals (Sweden)

    Kavvadia Smaragda

    2017-11-01

    Full Text Available Background/Aim: Class III malocclusion case are considered complex problems associated with unacceptable esthetics. The purpose of the present study was to assess the characteristics of the soft tissue profile and investigate the possible gender differences in adult Greeks with Class III malocclusion. Material and Methods: The material of the study comprised of 57 pretreatment lateral cephalograms of adult patients with Class III malocclusion aged 18 to 39 years. Eleven variables were assessed. The variables were measured and the mean, minimum and maximum and standard deviations were calculated. Parametric and non-parametric tests were used to compare males and females patients. Results: The total sample was characterized by concave skeletal profile. Male patients exhibited greater nose prominence and superior sulcus depth, longer distance from subnasale to the harmony line, more concave profile, thicker upper lip and larger upper lip strain. Conclusions: Many significant differences were noted in soft tissue characteristics between males and females with skeletal Class III malocclusion, suggesting possible gender dimorphism.

  6. Prediction of the outcome of orthodontic treatment of Class III malocclusions--a systematic review

    NARCIS (Netherlands)

    Fudalej, P.S.; Dragan, M.; Wedrychowska-Szulc, B.

    2011-01-01

    The purpose of this study was to systematically review the orthodontic literature to assess the effectiveness of a prediction of outcome of orthodontic treatment in subjects with a Class III malocclusion. A structured search of electronic databases, as well as hand searching, retrieved 232

  7. Inheritance of craniofacial features in Colombian families with class III malocclusion

    Directory of Open Access Journals (Sweden)

    L Otero

    2010-02-01

    Full Text Available L Otero, L Quintero, D Champsaur, E SimancaPontificia Universidad Javeriana, Bogotá, ColombiaIntroduction: The inheritance of class III malocclusion has been well documented, but the inheritance of craniofacial structures in Colombian families with this malocclusion has been not yet reported.Patients and methods: The study sample of 25 families comprised 186 untreated orthodontic individuals from 8 to 60 years old. Pedigrees were drawn using Cyrillic software. Complete family histories for each proband were ascertained and the affection status of relatives was confirmed by lateral cephalograms and facial and dental photographs. Analysis of variance and odds ratio test for each parameter was performed to estimate inheritance from parents to offspring and to determine similar phenotypic features in relatives.Results: The analysis of the pedigrees suggests autosomal dominant inheritance. The craniofacial characteristics that showed more resemblance between parents and offspring were middle facial height, shorter anterior cranial base and mandibular prognathism. In contrast the protrusion of upper lip and maxillary retrusion were the phenotypic features that contributed to class III in the majority of families.Conclusion: Knowledge of the inheritance of craniofacial phenotypes in class III malocclusion will enable the design of new therapies to treat this malocclusion.Keywords: inheritance, craniofacial, phenotype, class III malocclusion

  8. Factors influencing orthodontic treatment time for non-surgical Class III malocclusion.

    Science.gov (United States)

    Bichara, Lívia Monteiro; Aragón, Mônica Lídia Castro de; Brandão, Gustavo Antônio Martins; Normando, David

    2016-01-01

    To identify variables and their effect size on orthodontic treatment time of Class III malocclusion. Forty-five Class III malocclusion cases were selected from 2008 patients' records. Clinical charts, cephalometric radiographs, and pre and posttreatment dental casts were evaluated. Age, sex, PAR index at T1 and T2, overjet, missing teeth, extractions, number of treatment phases, missed appointments, appliance breakages, and cephalometric variables SNA, SNB, ANB, Wits, SnGoGn, CoA, CoGn, IMPA, 1.PP were investigated by multiple linear regression analysis and stepwise method at p2 (patients who missed more than 2 appointments), to detect the influence of this data on treatment time and the quality of the treatment (PAR T2). Average treatment time was 30.27 months. Multiple regression analysis showed that missed appointment (R2=0.4345) and appliance breakages (R2=0.0596) are the only variables able to significantly predict treatment duration. Treatment time for patients who missed more than 2 appointments was nearly one year longer. However, no significant influence on PAR T2 was observed for those patients. Orthodontic treatment duration in Class III patients is mainly influenced by factors related to patient compliance. Patients who missed more appointments did not show worse orthodontic finishing, but longer treatment. No occlusal, cephalometric, or demographic variable obtained before treatment was able to give some significant prediction about treatment time in Class III patients.

  9. 77 FR 45370 - Renewal of Agency Information Collection for Class III Gaming; Tribal Revenue Allocation Plans...

    Science.gov (United States)

    2012-07-31

    ... From the Federal Register Online via the Government Publishing Office DEPARTMENT OF THE INTERIOR Bureau of Indian Affairs Renewal of Agency Information Collection for Class III Gaming; Tribal Revenue Allocation Plans; Gaming on Trust Lands AGENCY: Bureau of Indian Affairs, Interior. ACTION: Notice of request...

  10. Identification of diverse archaeal proteins with class III signal peptides cleaved by distinct archaeal prepilin peptidases

    NARCIS (Netherlands)

    Szabó, Zalán; Oliveira Stahl, Adriana; Albers, Sonja-V.; Kissinger, Jessica C.; Driessen, Arnold J.M.; Pohlschröder, Mechthild; Pohlschroder, M.

    2007-01-01

    Most secreted archaeal proteins are targeted to the membrane via a tripartite signal composed of a charged N terminus and a hydrophobic domain, followed by a signal peptidase-processing site. Signal peptides of archaeal flagellins, similar to class III signal peptides of bacterial type IV pilins,

  11. Load Flow and Short Circuit Analysis of the Class III Power System of HANARO

    Energy Technology Data Exchange (ETDEWEB)

    Kim, H. K.; Jung, H. S

    2005-12-15

    The planning, design, and operation of electric power system require engineering studies to assist in the evaluation of the system performance, reliability, safety and economics. The Class III power of HANARO supplies power for not only HANARO but also RIPF and IMEF. The starting current of most ac motors is five to ten times normal full load current. The loads of the Class III power are connected in consecutive orders at an interval for 10 seconds to avoid excessive voltage drop. This technical report deals with the load flow study and motor starting study for the Class III power of HANARO using ETAP(Electrical Transient Analyzer Program) to verify the capacity of the diesel generator. Short-circuit studies are done to determine the magnitude of the prospective currents flowing throughout the power system at various time intervals after a fault occurs. Short-circuit studies can be performed at the planning stage in order to help finalize the system layout, determine voltage levels, and size cables, transformers, and conductors. From this study, we verify the short circuit current capacity of air circuit breaker(ACB) and automatic transfer switch(ATS) of the Class III power.

  12. Comparative evaluation of slot versus dovetail design in class III composite restorations in primary anterior teeth

    Directory of Open Access Journals (Sweden)

    Arun Rathnam

    2010-01-01

    It was concluded from the results that the both slot and dovetail types of cavity preparations were equally effacious when clinically reviewed for a period of 12 months. Hence the use of slot type of cavity preparation with reduced loss of the tooth structure is indicated for class III cavities in primary anterior teeth.

  13. Relationship between Class III malocclusion and hyoid bone displacement during swallowing: a cine-magnetic resonance imaging study.

    Science.gov (United States)

    Gokce, Sila Mermut; Gokce, Hasan Suat; Gorgulu, Serkan; Karacay, Seniz; Akca, Eralp; Olmez, Huseyin

    2012-08-01

    The displacement of the hyoid bone (HB) is a critical biomechanical component of the swallowing function. The aim of this study was to evaluate the swallowing-induced vertical and horizontal displacements of the HB in subjects with 2 different magnitudes of skeletal Class III malocclusion, by means of real-time, balanced turbo-field-echo (B-TFE) cine-magnetic resonance imaging. The study population comprised 19 patients with mild skeletal Class III malocclusion, 16 with severe skeletal Class III malocclusion, and 20 with a skeletal Class I relationship. Before the commencement of the study, all subjects underwent cephalometric analysis to identify the nature of skeletal malformations. B-TFE images were obtained for the 4 consecutive stages of deglutition as each patient swallowed 10 mL of water, and the vertical and horizontal displacements of the HB were measured at each stage. At all stages of swallowing, the vertical position of the HB in the severe Class III malocclusion group was significantly lower than those in the mild Class III and Class I malocclusion groups. Similarly, the horizontal displacement of the HB was found to be significantly associated with the severity of malocclusion, i.e., the degree of Class III malocclusion, while the amount of anterior displacement of the HB decreased with an increase in the severity of the Class III deformity. Our findings indicate the existence of a relationship between the magnitude of Class III malocclusion and HB displacement during swallowing.

  14. HLA and fertility

    Energy Technology Data Exchange (ETDEWEB)

    Ober, C. [Univ. of Chicago, IL (United States)

    1995-11-01

    The recent paper by Jin et al., reporting that class 11 region major histocompatibility complex genes may influence embryonic loss in outbred couples supports previous results of our studies of HLA and fertility in the Hutterites. However, the authors have incorrectly cited our work and have omitted the reference that is most relevant to their results. The paper by Kostyu et al. is incorrectly referred to in the introduction as providing evidence for HLA sharing being associated with recurrent spontaneous abortion. The Kostyu et al. paper does not include any data on fertility or reproduction but reports frequencies of individuals who are homozygous at the HLA-A, -C, -B, -DR, and -DQ loci in the Hutterite population. In fact, recurrent spontaneous abortion has not been observed in any of the couples in our sample of >500 Hutterite couples. References more appropriate to the association between HLA sharing and recurrent miscarriage are those by Komlos et al., Schacter et al., Gerencer and Kastelan, and Beer et al. It might also be worth pointing out that many studies of recurrent miscarriage in outbred couples have not found an association with HLA sharing; examples include the studies of Ergolu et al., Oksenberg et al., and Christiansen et al., among others. 11 refs.

  15. Early orthodontic treatment for Class III malocclusion: A systematic review and meta-analysis.

    Science.gov (United States)

    Woon, See Choong; Thiruvenkatachari, Badri

    2017-01-01

    Class III malocclusion affects between 5% and 15% of our population. The 2 most common dilemmas surrounding Class III treatment are the timing of treatment and the type of appliance. A number of appliances have been used to correct a Class III skeletal discrepancy, but there is little evidence available on their effectiveness in the long term. Similarly, early treatment of Class III malocclusion has been practiced with increasing interest. However, there has been no solid evidence on the benefits in the long term. The aim of this systematic review was to evaluate the effectiveness of orthodontic/orthopedic methods used in the early treatment of Class III malocclusion in the short and long terms. Several sources were used to identify all relevant studies independently of language. The Cochrane Central Register of Controlled Trials, Cochrane Database of Systematic Reviews, Embase (Ovid), and MEDLINE (Ovid) were searched to June 2016. The selection criteria included randomized controlled trials (RCTs) and prospective controlled clinical trials (CCTs) of children between the ages of 7 and 12 years on early treatment with any type of orthodontic/orthopedic appliance compared with another appliance to correct Class III malocclusion or with an untreated control group. The primary outcome measure was correction of reverse overjet, and the secondary outcomes included skeletal changes, soft tissue changes, quality of life, patient compliance, adverse effect, Peer Assessment Rating score, and treatment time. The search results were screened for inclusion, and the data extracted by 2 independent authors. The data were analyzed using software (version 5.1, Review Manager; The Nordic Cochrane Centre, The Cochrane Collaboration; Copenhagen, Denmark). The mean differences with 95% confidence intervals were expressed for the continuous data. Random effects were carried out with high levels of clinical or statistical heterogeneity and fixed affects when the heterogeneity was low

  16. Base of the skull morphology and Class III malocclusion in patients with unilateral cleft lip and palate.

    Science.gov (United States)

    Tinano, Mariana Maciel; Martins, Milene Aparecida Torres Saar; Bendo, Cristiane Baccin; Mazzieiro, Ênio

    2015-01-01

    The aim of the present study was to determine the morphological differences in the base of the skull of individuals with cleft lip and palate and Class III malocclusion in comparison to control groups with Class I and Class III malocclusion. A total of 89 individuals (males and females) aged between 5 and 27 years old (Class I, n = 32; Class III, n = 29; and Class III individuals with unilateral cleft lip and palate, n = 28) attending PUC-MG Dental Center and Cleft Lip/Palate Care Center of Baleia Hospital and PUC-MG (CENTRARE) were selected. Linear and angular measurements of the base of the skull, maxilla and mandible were performed and assessed by a single calibrated examiner by means of cephalometric radiographs. Statistical analysis involved ANCOVA and Bonferroni correction. No significant differences with regard to the base of the skull were found between the control group (Class I) and individuals with cleft lip and palate (P > 0.017). The cleft lip/palate group differed from the Class III group only with regard to CI.Sp.Ba (P = 0.015). Individuals with cleft lip and palate had a significantly shorter maxillary length (Co-A) in comparison to the control group (P Class I or Class III and individuals with cleft lip and palate and Class III malocclusion.

  17. Prevalence of class III malocclusion and crossbite among children and adolescents with craniomandibular dysfunction.

    Science.gov (United States)

    Popovic, Nenad; Drinkuth, Nicole; Toll, Douglas E

    2014-01-01

    Numerous studies have been devoted to the causes of craniomandibular dysfunction (CMD). This investigation addressed the effect of class III malocclusion and crossbite on CMD based on a sample of 115 prepubertal and adolescent patients of both sexes. Although class III malocclusion only accounted for 12.2% of the total sample, thus, being the smallest group, the percentage of crossbite (71.4%) among these patients was disproportionately higher than among the other classes. Of the total sample, the prevalence of crossbite was 30.4%. We compared these findings to a large-scale (n=4727) study by Thilander et al. (2002), who reported a strikingly high percentage of class I patients compared to our findings (72.7% versus 27.8%) and a lower percentage of crossbite cases (8.0% versus 30.4%). In accordance with the "orthodontic risk child" concept by Grabowski et al. (2007) and Stahl et al. (2007), we conclude that class III malocclusion and crossbite are keys in the pathogenesis of CMD.

  18. Evaluation of temporomandibular disorders in Class III patients treated with mandibular cervical headgear and fixed appliances.

    Science.gov (United States)

    Rey, Diego; Oberti, Giovanni; Baccetti, Tiziano

    2008-03-01

    Our aim in this study was to evaluate the prevalence of temporomandibular disorders (TMD) in Class III patients treated with mandibular cervical headgear (MCH) and fixed appliances. The sample of 75 patients included 25 patients with no previous orthodontic treatment, 25 Class I patients who had undergone orthodontic treatment with fixed appliances and without extractions, and 25 patients with dentoskeletal Class III disharmonies treated with MCH and fixed appliances. The Helkimo index was used to test the prevalence of TMD symptoms in the 3 groups. The prevalence rates of the Helkimo index in the 3 groups were compared with the z score on proportions. No statistically significant differences in the prevalence rates of the Helkimo index scores in the 3 groups were found (P = .367). Most subjects in the 3 groups had an Helkimo index of zero (66.7%). Subjects with Class III malocclusions treated with MCH and fixed appliances do not have greater prevalence of TMD symptoms than do Class I subjects treated with fixed appliances or untreated subjects.

  19. An Eectromyographic Ccomparison Between the Activities of Temporal and Masseter Muscles in Class III Skeletal

    Directory of Open Access Journals (Sweden)

    T Hossein-Zadeh-Nik

    2002-02-01

    Full Text Available Electromyographic (EMG investigations about the activities of the muscles have been the focus of attention for many years. In the field of orthodontics, investigators, among other things, tried to evaluate correlation between EMG activity, occlusal relationships and craniofacial morphology to analyze the effect of muscular activity, as an etiological factor in malocclusion. The purpose of the present investigation is to analyze the effect of EMG activity of temporal and masseter muscles quantitatively in skeletal class III malocclusion. 26 patients (9 to If years old, with class III malocclusion were selected and their EMG activity of temporal and masseter muscles in rest position, centric occlusion, clenching, mastication and swallowing were compared with 20 normal children at the same age range. Then the statistical correlation between 13 cephalometric parameters and EMG activities were analyzed and then the regression analysis was performed and the results were as follows:1- The mean amplitude of masseter and temporal muscles activity in rest position, centric occlusion, mastication, and clenching in class III samples were greater than normal group (PO.05.2- The mean duration of masseter and temporal muscles activity in rest position and centric occlusion in class III samples were more than normal group (PO.05.3- According to regression analysis, a linear correlation was observed between ANB angle and temporal muscle activity in rest and centric occlusion that was not observed in other cases.The findings of this study showed that difference in temporal muscle activity in class III malocclusion, in comparison with the normal group, is correlated with skeletal morphology of the face, but according to other investigations it is not ture for the masseter muscle.

  20. Nonsurgical Treatment of a Class III Patient with Alt-RAMEC Protocol and Facemask Therapy

    Directory of Open Access Journals (Sweden)

    Saurabh Chaturvedi

    2013-01-01

    Full Text Available Class III malocclusion has been the subject of interest in many investigations because of the challenges in its treatment. The skeletal manifestation can be due to mandibular anterior positioning (prognathism or growth excess (macrognathia, maxillary posterior positioning (retrognathism or growth deficiency (micrognathia, or a combination of mandibular and maxillary discrepancies. A 15-year-old Asian with a skeletal Class III malocclusion and a severe anterior crossbite was treated with Alt-RAMEC protocol designed to loosen the sutures that connect the maxilla to the surrounding bones via rapid expansion and contraction on an alternating weekly basis and facemask therapy. An Angle Class I molar relationship was achieved with canine protected occlusion and incisal guidance. A wrap-around retainer was placed on the maxillary arch and a lingual bonded retainer on the mandibular arch. Treatment time was 30 months.

  1. Orthodontic retreatment using anchorage with miniplate to camouflage a Class III skeletal pattern.

    Science.gov (United States)

    Farret, Marcel Marchiori

    2016-06-01

    This manuscript describes the treatment of a 27-year-old patient who was previously treated with two maxillary first premolar extractions. The patient had skeletal Class III malocclusion, Class III canine relationship, anterior crossbite, and a concave profile. As the patient refused orthognathic surgery, a miniplate was used on the right side of the lower arch as an anchorage unit after the extraction of mandibular first premolars, aiding the retraction of anterior teeth. At the end of treatment, anterior crossbite was corrected, in which first molars and canines were in a Class I relationship, and an excellent intercuspation was reached. Furthermore, patient's profile remarkably improved as a result of mandibular incisor retraction. A 30-month follow-up showed good stability of the results obtained. This case was presented to the Brazilian Board of Orthodontics and Dentofacial Orthopedics (BBO) as one of the requirements to become diplomate by the BBO.

  2. Orthodontic camouflage of skeletal Class III malocclusion with miniplate: a case report.

    Science.gov (United States)

    Farret, Marcel Marchiori; Farret, Milton M Benitez; Farret, Alessandro Marchiori

    2016-01-01

    Skeletal Class III malocclusion is often referred for orthodontic treatment combined with orthognathic surgery. However, with the aid of miniplates, some moderate discrepancies become feasible to be treated without surgery. To report the case of a 24-year-old man with severe skeletal Angle Class III malocclusion with anterior crossbite and a consequent concave facial profile. The patient refused to undergo orthognathic surgery; therefore, orthodontic camouflage treatment with the aid of miniplates placed on the mandibular arch was proposed. After 18 months of treatment, a Class I molar and canine relationship was achieved, while anterior crossbite was corrected by retraction of mandibular teeth. The consequent decrease in lower lip fullness and increased exposure of maxillary incisors at smiling resulted in a remarkable improvement of patient's facial profile, in addition to an esthetically pleasing smile, respectively. One year later, follow-up revealed good stability of results.

  3. Orthodontic retreatment using anchorage with miniplate to camouflage a Class III skeletal pattern

    Directory of Open Access Journals (Sweden)

    Marcel Marchiori Farret

    Full Text Available ABSTRACT This manuscript describes the treatment of a 27-year-old patient who was previously treated with two maxillary first premolar extractions. The patient had skeletal Class III malocclusion, Class III canine relationship, anterior crossbite, and a concave profile. As the patient refused orthognathic surgery, a miniplate was used on the right side of the lower arch as an anchorage unit after the extraction of mandibular first premolars, aiding the retraction of anterior teeth. At the end of treatment, anterior crossbite was corrected, in which first molars and canines were in a Class I relationship, and an excellent intercuspation was reached. Furthermore, patient's profile remarkably improved as a result of mandibular incisor retraction. A 30-month follow-up showed good stability of the results obtained. This case was presented to the Brazilian Board of Orthodontics and Dentofacial Orthopedics (BBO as one of the requirements to become diplomate by the BBO.

  4. Management of severe skeletal Class III malocclusion with bimaxillary orthognathic surgery

    Directory of Open Access Journals (Sweden)

    Jitesh Haryani

    2016-01-01

    Full Text Available Orthognathic surgery in conjunction with fixed orthodontics is a common indication for interdisciplinary management of severe skeletal Class III malocclusion. A thorough analysis of pretreatment investigations and development of a surgical visual treatment objective is essential to plan the type of surgical technique required. Bimaxillary orthognathic surgery is the most common type of surgical procedure for severe skeletal discrepancies. The present case report is a combined ortho-surgical team management of a skeletally Class III patient. The severity of the case required bilateral upper first premolar extraction for dentoalveolar decompensation and simultaneous “Two-jaw surgery” with maxillary advancement of 4 mm and mandibular setback of 7 mm. Postsurgery, a pleasing good facial profile was achieved with Class II molar relation and positive overjet.

  5. 正常妊娠のtrophoblastにおけるMHC抗原, とくにHLA Class II抗原の表現に関する免疫組織学的解析

    OpenAIRE

    本間, 滋; 遠藤, 道仁; 内山, 三枝子; 中村, 稔; 金沢, 浩二; 竹内, 正七; Shigeru, HONMA; Michihito, ENDOU; Mieko, UCHIYAMA; Minoru, Nakamura; Koji, KANAZAWA; Shoshichi, TAKEUCHI; 新潟大学医学部産科婦人科学教室; Department of Obstetrics and Gynecology School of Medicine, Niigata University

    1989-01-01

    着床部trophoblastにおけるMHC抗原, とくにclass II HLAの表現の有無を明らかにする目的で, 摘出妊娠初期子宮と満期正常分娩にて得られた胎盤の着床部組織について単クローン抗体(抗HLA-DR, -DP, -DQ抗体)を用いた免疫組織学的解析を行つた. 同時に連続組織切片についてtrophoblastを識別する抗cytokeratin(CAM5.2)を用いた染色を行い, trophoblastのsubpopulationに十分留意し, さらに, HLA-ABCの染色を行つて以下の成績を得た. 妊娠初期 (1) villous syncytiotrophoblastはHLA-ABC, -DR, -DP, -DQのいずれも陰性であつたが, villous cytotrophoblastはHLA-ABC, -DR, -DQについては陰性であるものの, -DPは陽性であつた. (2) cell island, cytotrophoblastic cell columnのcytotrophoblastはHLA-ABC, -DP陽性を示したが, -DR, -DQ陰性であつ...

  6. First trimester human endovascular trophoblast cells express both HLA-C and HLA-G.

    Science.gov (United States)

    Pröll, J; Blaschitz, A; Hutter, H; Dohr, G

    1999-07-01

    In human pregnancies, trophoblasts, in contrast to placental connective tissue and the fetus itself, come into direct contact with the maternal allorecognizing system at special sites. Villous syncytiotrophoblasts washed around by maternal blood lack HLA class I proteins, whereas extravillous trophoblasts, which deeply invade maternal uterine tissues, express high amounts of HLA-G and also HLA-C, the latter to a lesser degree, however. A subpopulation of extravillous trophoblasts, the endovascular trophoblast, enters maternal spiral artery lumen and, like syncytiotrophoblast, comes into direct contact with maternal blood. Less is known about HLA class I distribution on this endovascular trophoblast subpopulation. A comparative immununohistochemical analysis was done on decidual cryo-sections containing trophoblast-invaded spiral arteries using different anti-HLA class I monoclonal antibodies (mAbs) and a peroxidase-labeled streptavidinbiotin detection system. MAbs W6/32 (anti-HLA-A, -B, -C, -G), HCA2 (anti-HLA-A, -G) G233 and 87G (both anti-HLA-G) resulted in strong positivity on endovascular trophoblasts. L31 (anti-HLA-C) and HC10 (anti-HLA-B, -C) revealed clear positivity, whereas TU149 (anti-HLA-B, -C, some -A) produced a heterogeneous staining pattern, faintly positive on some endovascular trophoblastic cells and negative on others. MAb LA45 (anti-HLA-A, -B) did not bind to any endovascular trophoblast, neither did BFL.1 (anti-HLA-G) nor 16G1 (anti-HLA-G, soluble). This study shows that trophoblastic cells belonging to the endovascular subpopulation express considerable amounts of HLA-G and slightly less HLA-C.

  7. Identification of GAD65 AA 114-122 reactive 'memory-like' NK cells in newly diagnosed Type 1 diabetic patients by HLA-class I pentamers.

    Science.gov (United States)

    Perri, Valentina; Gianchecchi, Elena; Cifaldi, Loredana; Pellegrino, Marsha; Giorda, Ezio; Andreani, Marco; Cappa, Marco; Fierabracci, Alessandra

    2017-01-01

    Type 1 diabetes is an autoimmune disease, in which pancreatic β cells are destroyed by autoreactive T cells in genetically predisposed individuals. Serum beta cell autoantibody specificities have represented the mainstay for classifying diabetes as autoimmune-mediated and for stratifying risk in first-degree relatives. In recent years, approaches were attempted to solve the difficult issue of detecting rare antigen-specific autoreactive T cells and their significance to etiopathogenesis such as the use of the MHC multimer technology. This tool allowed the specific detection of increased percentages of GAD65 autoreactive T cells by means of HLA A*02:01 GAD65 AA 114-122 pentamers in newly diagnosed diabetics. Here we provide evidence that GAD65 AA 114-122 pentamers can depict a GAD65 AA114-122 peptide expandable population of functionally and phenotypically skewed, preliminary characterized CD3-CD8dullCD56+ 'memory-like' NK cells in PBMC of newly diagnosed diabetics. Our data suggest that the NK cell subset could bind the HLA class I GAD65 AA 114-122 pentamer through ILT2 inhibitory receptor. CD107a expression revealed increased degranulation of CD3-CD8dullCD56+ NK cells in GAD65 AA 114-122 and FLU peptide expanded peripheral blood mononuclear cells of diabetics following GAD65 AA 114-122 peptide HLA A*02:01 presentation in respect to the unpulsed condition. CD107a expression was enriched in ILT2 positive NK cells. As opposite to basal conditions where similar percentages of CD3-CD56+ILT2+ cells were detected in diabetics and controls, CD3-CD56+CD107a+ and CD3-CD56+ILT2+CD107a+ cells were significantly increased in T1D PBMC either GAD65 AA 114-122 or FLU peptides stimulated after co-culture with GAD65 AA 114-122 pulsed APCs. As control, healthy donor NK cells showed similar degranulation against both GAD65 AA 114-122 pulsed and unpulsed APCs. The pathogenetic significance of the CD3-CD8dullCD56+ 'memory-like NK cell subset' with increased response upon secondary

  8. Comparative genomic structure of human, dog, and cat MHC: HLA, DLA, and FLA.

    Science.gov (United States)

    Yuhki, Naoya; Beck, Thomas; Stephens, Robert; Neelam, Beena; O'Brien, Stephen J

    2007-01-01

    Comparisons of the genomic structure of 3 mammalian major histocompatibility complexes (MHCs), human HLA, canine DLA, and feline FLA revealed remarkable structural differences between HLA and the other 2 MHCs. The 4.6-Mb HLA sequence was compared with the 3.9-Mb DLA sequence from 2 supercontigs generated by 7x whole-genome shotgun assembly and 3.3-Mb FLA draft sequence. For FLA, we confirm that 1) feline FLA was split into 2 pieces within the TRIM (member of the tripartite motif) gene family found in human HLA, 2) class II, III, and I regions were placed in the pericentromeric region of the long arm of chromosome B2, and 3) the remaining FLA was located in subtelomeric region of the short arm of chromosome B2. The exact same chromosome break was found in canine DLA structure, where class II, III, and I regions were placed in a pericentromeric region of chromosome 12 whereas the remaining region was located in a subtelomeric region of chromosome 35, suggesting that this chromosome break occurred once before the split of felid and canid more than 55 million years ago. However, significant differences were found in the content of genes in both pericentromeric and subtelomeric regions in DLA and FLA, the gene number, and amplicon structure of class I genes plus 2 other class I genes found on 2 additional chromosomes; canine chromosomes 7 and 18 suggest the dynamic nature in the evolution of MHC class I genes.

  9. Má oclusão de Classe I de Angle, com tendência à classe III esquelética, tratada com controle de crescimento Angle Class I malocclusion, with class III skeletal tendency, treated with growth control

    Directory of Open Access Journals (Sweden)

    Ademir Roberto Brunetto

    2009-10-01

    Full Text Available A má oclusão de Classe III de Angle é caracterizada por uma relação dentária anteroposterior inadequada, que pode ou não estar acompanhada de alterações esqueléticas. Em geral, o aspecto facial fica bastante comprometido, principalmente quando associada à deficiência no terço médio da face, sendo esse, na maioria das vezes, o principal fator que motiva o paciente a procurar tratamento. Este caso foi apresentado à Diretoria do Board Brasileiro de Ortodontia e Ortopedia Facial (BBO, representando a categoria livre, como parte dos requisitos para a obtenção do título de Diplomado pelo BBO.Angle Class III malocclusion is characterized by an anteroposterior dental alteration, which might be accompanied by skeletal deformities. Usually, the facial aspect becomes aesthetically compromised, mostly when the middle third of the face is affected (this is the main reason why patients seek for treatment.This case was presented to the directorship of the Brazilian Board of Orthodontics and Facial Orthopedics (BBO, standing for the free category, as a part of the requirements to obtain the Board's Certificate.

  10. Má oclusão Classe III de Angle com discrepância anteroposterior acentuada Angle Class III malocclusion with severe anteroposterior discrepancy

    Directory of Open Access Journals (Sweden)

    Carlos Alexandre Câmara

    2010-04-01

    Full Text Available O caso clínico apresentado refere-se ao tratamento de uma paciente com 36 anos, que apresentava uma má oclusão Classe III esquelética e dentária, com ausência dos caninos superiores. Foi realizado um tratamento ortodôntico-cirúrgico combinado, com avanço de maxila (Le Fort 1 e ajustes oclusais nos primeiros pré-molares superiores, que substituíram os caninos. Esse caso foi apresentado à Diretoria do Board Brasileiro de Ortodontia e Ortopedia Facial (BBO, representando a categoria 4, ou seja, uma má oclusão com discrepância anterossuperior acentuada, como parte dos requisitos para a obtenção do título de Diplomado pelo BBO.This case report describes the treatment of a 36-year-old patient who presented a skeletal and dental Class III malocclusion and missing upper canines. The patient was treated with orthosurgical maxillary advancement (Le Fort 1 and occlusal adjustment of the first premolars, which replaced the canines. This case was presented to the Brazilian Board of Orthodontics and Facial Orthopedics (BBO, as representative of Category 4, i.e., malocclusion with severe anteroposterior discrepancy, as part of the requirements for obtaining the BBO Diploma.

  11. Lower incisor dentoalveolar compensation and symphysis dimensions among Class I and III malocclusion patients with different facial vertical skeletal patterns.

    Science.gov (United States)

    Molina-Berlanga, Núria; Llopis-Perez, Jaume; Flores-Mir, Carlos; Puigdollers, Andreu

    2013-11-01

    To compare lower incisor dentoalveolar compensation and mandible symphysis morphology among Class I and Class III malocclusion patients with different facial vertical skeletal patterns. Lower incisor extrusion and inclination, as well as buccal (LA) and lingual (LP) cortex depth, and mandibular symphysis height (LH) were measured in 107 lateral cephalometric x-rays of adult patients without prior orthodontic treatment. In addition, malocclusion type (Class I or III) and facial vertical skeletal pattern were considered. Through a principal component analysis (PCA) related variables were reduced. Simple regression equation and multivariate analyses of variance were also used. Incisor mandibular plane angle (P malocclusion groups. Variations in the mandibular plane have a negative correlation with LA (Class I P  =  .03 and Class III P  =  .01) and a positive correlation with LH (Class I P  =  .01 and Class III P  =  .02) in both groups. Within the Class III group, there was a negative correlation between the mandibular plane and LP (P  =  .02). PCA showed that the tendency toward a long face causes the symphysis to elongate and narrow. In Class III, alveolar narrowing is also found in normal faces. Vertical facial pattern is a significant factor in mandibular symphysis alveolar morphology and lower incisor positioning, both for Class I and Class III patients. Short-faced Class III patients have a widened alveolar bone. However, for long-faced and normal-faced Class III, natural compensation elongates the symphysis and influences lower incisor position.

  12. Rapid HLA class I DNA typing using microtiter plate-reverse hybridization assay (MRHA) by simple thermoregulation: high-resolution subtyping of the HLA-A2 and -B40 antigen groups.

    Science.gov (United States)

    Moribe, T; Kaneshige, T; Inagawa, A; Nakatani, S; Hirai, H; Morita, F; Ito, Y; Inoko, H

    1999-06-01

    We have established a precise, rapid, simple and economical subtyping method for alleles encoding the HLA-A2 and -B40 antigens using microtiter plate-reverse hybridization assay (MRHA), which is based on the general principle of HLA oligotyping by reverse dot blot hybridization. Amino-modified sequence-specific oligonucleotide (SSO) probes were immobilized covalently onto a carboxylate-modified microtiter plate. In order to perform high-resolution subtyping of the HLA-A2 and -B40 antigen groups, the alpha1 and alpha2 domain regions were amplified using a pair of group-specific primers composed of an unlabeled sense primer and a biotinylated antisense primer. PCR-amplified products were hybridized with SSO probes in hybridization buffer containing formamide for 1 hour at 37 degrees C. After washing with 2 X SSC at room temperature, the bound PCR products were detected by alkaline phosphatase-conjugated streptavidine followed by color development. All of 8 HLA-B40 suballeles, all of 2 HLA-B47 suballeles (B40 group-specific primers used in this study allowed also B47 amplification) and 17 out of 21 HLA-A2 suballeles were discriminated. The remaining four HLA-A2 suballeles were determined by analysis after exon 4 amplification. HLA-DNA typing by this method was easily and exactly performed regardless of sample number. The greatest advantages of this technique are strong positive signals obtained, reproducibility and the ease of thermoregulation for hybridization and washing as compared to previously reported microtiter plate hybridization methods.

  13. [Study of anterior alveolar bone thickness in skeletal class III malocclusion patients with orthognathic surgery].

    Science.gov (United States)

    Zhang, Jie; Li, Xiao-tong

    2016-02-18

    To investigate the compensation of the anterior alveolar bone thickness in skeletal class III patients treated with orthodontic-surgical treatment. The samples consisted of 54 skeletal class III patients treated with orthodontic-surgical treatment. Lateral cephalograms were taken before treatment. Descriptive statistics were calculated for corresponding variables, and the differences between the samples and the norms from Peking University normal occlusion sample library were assessed by independent-sample t test. Correlation analyses were performed to find associations between skeletal characteristics and anterior alveolar bone thickness. According to skeletal anteroposterior discrepancy/vertical type (ANB, criteria=-4°; SN-MP, criteria=37.7°), the samples were allocated into group A (severe anteroposterior discrepancy/hypodivergent vertical type, n=11), group B (moderate anteroposterior discrepancy/hypodivergent vertical type, n=16), group C (severe anteroposterior discrepancy/hyperdivergent vertical type, n=14), and group D (moderate anteroposterior discrepancy/hyperdivergent vertical type, n=13),and one-way ANOVA with SNK multiple comparison test were performed. The anterior alveolar bone thickness of the skeletal class III patients were thinner compared with norm values (Pclass III patients are thinner compared with normal occlusion. Different skeletal anteroposterior discrepancy/vertical type results in differences in the anterior alveolar bone thickness, so decompensation should be treated differently and carefully.

  14. Unraveling multiple MHC gene associations with systemic lupus erythematosus: model choice indicates a role for HLA alleles and non-HLA genes in Europeans.

    Science.gov (United States)

    Morris, David L; Taylor, Kimberly E; Fernando, Michelle M A; Nititham, Joanne; Alarcón-Riquelme, Marta E; Barcellos, Lisa F; Behrens, Timothy W; Cotsapas, Chris; Gaffney, Patrick M; Graham, Robert R; Pons-Estel, Bernardo A; Gregersen, Peter K; Harley, John B; Hauser, Stephen L; Hom, Geoffrey; Langefeld, Carl D; Noble, Janelle A; Rioux, John D; Seldin, Michael F; Criswell, Lindsey A; Vyse, Timothy J

    2012-11-02

    We have performed a meta-analysis of the major-histocompatibility-complex (MHC) region in systemic lupus erythematosus (SLE) to determine the association with both SNPs and classical human-leukocyte-antigen (HLA) alleles. More specifically, we combined results from six studies and well-known out-of-study control data sets, providing us with 3,701 independent SLE cases and 12,110 independent controls of European ancestry. This study used genotypes for 7,199 SNPs within the MHC region and for classical HLA alleles (typed and imputed). Our results from conditional analysis and model choice with the use of the Bayesian information criterion show that the best model for SLE association includes both classical loci (HLA-DRB1(∗)03:01, HLA-DRB1(∗)08:01, and HLA-DQA1(∗)01:02) and two SNPs, rs8192591 (in class III and upstream of NOTCH4) and rs2246618 (MICB in class I). Our approach was to perform a stepwise search from multiple baseline models deduced from a priori evidence on HLA-DRB1 lupus-associated alleles, a stepwise regression on SNPs alone, and a stepwise regression on HLA alleles. With this approach, we were able to identify a model that was an overwhelmingly better fit to the data than one identified by simple stepwise regression either on SNPs alone (Bayes factor [BF] > 50) or on classical HLA alleles alone (BF > 1,000). Copyright © 2012 The American Society of Human Genetics. Published by Elsevier Inc. All rights reserved.

  15. Class III phosphoinositide 3-kinase/VPS34 and dynamin are critical for apical endocytic recycling.

    Science.gov (United States)

    Carpentier, Sarah; N'Kuli, Francisca; Grieco, Giuseppina; Van Der Smissen, Patrick; Janssens, Virginie; Emonard, Hervé; Bilanges, Benoît; Vanhaesebroeck, Bart; Gaide Chevronnay, Héloïse P; Pierreux, Christophe E; Tyteca, Donatienne; Courtoy, Pierre J

    2013-08-01

    Recycling is a limiting step for receptor-mediated endocytosis. We first report three in vitro or in vivo evidences that class III PI3K/VPS34 is the key PI3K isoform regulating apical recycling. A substractive approach, comparing in Opossum Kidney (OK) cells a pan-class I/II/III PI3K inhibitor (LY294002) with a class I/II PI3K inhibitor (ZSTK474), suggested that class III PI3K/VPS34 inhibition induced selective apical endosome swelling and sequestration of the endocytic receptor, megalin/LRP-2, causing surface down-regulation. GFP-(FYVE)x2 overexpression to sequester PI(3)P caused undistinguishable apical endosome swelling. In mouse kidney proximal tubular cells, conditional Vps34 inactivation also led to vacuolation and intracellular megalin redistribution. We next report that removal of LY294002 from LY294002-treated OK cells induced a spectacular burst of recycling tubules and restoration of megalin surface pool. Acute triggering of recycling tubules revealed recruitment of dynamin-GFP and dependence of dynamin-GTPase, guidance directionality by microtubules, and suggested that a microfilamentous net constrained endosomal swelling. We conclude that (i) besides its role in endosome fusion, PI3K-III is essential for endosome fission/recycling; and (ii) besides its role in endocytic entry, dynamin also supports tubulation of recycling endosomes. The unleashing of recycling upon acute reversal of PI3K inhibition may help study its dynamics and associated machineries. © 2013 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  16. 40 CFR 144.21 - Existing Class I, II (except enhanced recovery and hydrocarbon storage) and III wells.

    Science.gov (United States)

    2010-07-01

    ... recovery and hydrocarbon storage) and III wells. 144.21 Section 144.21 Protection of Environment... hydrocarbon storage) and III wells. (a) An existing Class I, II (except enhanced recovery and hydrocarbon... decision; or (9) For Class II wells (except enhanced recovery and hydrocarbon storage), five years after...

  17. The Populus Class III HD ZIP transcription factor POPCORONA affects cell differentiation during secondary growth of woody stems

    Science.gov (United States)

    Juan Du; Eriko Miura; Ma