140 research outputs found
Multiplicity dependence of (anti-)deuteron production in pp collisions at root s=7 TeV
none1019siIn this letter, the production of deuterons and anti-deuterons in pp collisions at root s = 7 TeV is studied as a function of the charged-particle multiplicity density at mid-rapidity with the ALICE detector at the LHC. Production yields are measured at mid-rapidity in five multiplicity classes and as a function of the deuteron transverse momentum (p(T)). The measurements are discussed in the context of hadron-coalescence models. The coalescence parameter B-2, extracted from the measured spectra of (anti-)deuteronsand primary (anti-)protons, exhibits no significant p(T)-dependence for p(T) < 3 GeV/c, in agreement with the expectations of a simple coalescence picture. At fixed transverse momentum per nucleon, the B-2 parameter is found to decrease smoothly from low multiplicity pp to Pb-Pb collisions, in qualitative agreement with more elaborate coalescence models. The measured mean transverse momentum of (anti-)deuterons in pp is not reproduced by the Blast-Wave model calculations that simultaneously describe pion, kaon and proton spectra, in contrast to central Pb-Pb collisions. The ratio between the p(T)-integrated yield of deuterons to protons, d/p, is found to increase with the charged-particle multiplicity, as observed in inelastic pp collisions at different centre-of-mass energies. The d/p ratios are reported in a wide range, from the lowest to the highest multiplicity values measured in pp collisions at the LHC. (C) 2019 The Author(s). Published by Elsevier B.VnoneAcharya, S.; Acosta, F. T.; Adamova, D.; Adhya, S. P.; Adler, A.; Adolfsson, J.; Aggarwal, M. M.; Rinella, G. Aglieri; Agnello, M.; Ahammed, Z.; Ahmad, S.; Ahn, S. U.; Aiola, S.; Akindinov, A.; Al-Turany, M.; Alam, S. N.; Albuquerque, D. S. D.; Aleksandrov, D.; Alessandro, B.; Alfanda, H. M.; Alfaro Molina, R.; Ali, B.; Ali, Y.; Alici, A.; Alkin, A.; Alme, J.; Alt, T.; Altenkamper, L.; Altsybeev, I; Anaam, M. N.; Andrei, C.; Andreou, D.; Andrews, H. A.; Andronic, A.; Angeletti, M.; Anguelov, V; Anson, C.; Anticic, T.; Antinori, F.; Antonioli, P.; Anwar, R.; Apadula, N.; Aphecetche, L.; Appelshaeuser, H.; Arcelli, S.; Arnaldi, R.; Arratia, M.; Arsene, I. C.; Arslandok, M.; Augustinus, A.; Averbeck, R.; Azmi, M. D.; Badala, A.; Baek, Y. W.; Bagnasco, S.; Bailhache, R.; Bala, R.; Baldisseri, A.; Ball, M.; Baral, R. C.; Barbera, R.; Barioglio, L.; Barnafoldi, G. G.; Barnby, L. S.; Barret, V; Bartalini, P.; Barth, K.; Bartsch, E.; Bastid, N.; Basu, S.; Batigne, G.; Batyunya, B.; Batzing, P. C.; Bauri, D.; Bazo Alba, J. L.; Bearden, I. G.; Bedda, C.; Behera, N. K.; Belikov, I; Bellini, F.; Bello Martinez, H.; Bellwied, R.; Beltran, L. G. E.; Belyaev, V; Bencedi, G.; Beole, S.; Bercuci, A.; Berdnikov, Y.; Berenyi, D.; Bertens, R. A.; Berzano, D.; Betev, L.; Bhasin, A.; Bhat, I. R.; Bhatt, H.; Bhattacharjee, B.; Bianchi, A.; Bianchi, L.; Bianchi, N.; Bielcik, J.; Bielcikova, J.; Bilandzic, A.; Biro, G.; Biswas, R.; Biswas, S.; Blair, J. T.; Blau, D.; Blume, C.; Boca, G.; Bock, F.; Bogdanov, A.; Boldizsar, L.; Bolozdynya, A.; Bombara, M.; Bonomi, G.; Bonora, M.; Borel, H.; Borissov, A.; Borri, M.; Botta, E.; Bourjau, C.; Bratrud, L.; Braun-Munzinger, P.; Bregant, M.; Broker, T. A.; Broz, M.; Brucken, E. J.; Bruna, E.; Bruno, G. E.; Buckland, M. D.; Budnikov, D.; Buesching, H.; Bufalino, S.; Buhler, P.; Buncic, P.; Busch, O.; Buthelezi, Z.; Butt, J. B.; Buxton, J. T.; Caffarri, D.; Caines, H.; Caliva, A.; Calvo Villar, E.; Camacho, R. S.; Camerini, P.; Capon, A. A.; Carnesecchi, F.; Castellanos, J. Castillo; Castro, A. J.; Casula, E. A. R.; Sanchez, C. Ceballos; Chakraborty, P.; Chandra, S.; Chang, B.; Chang, W.; Chapeland, S.; Chartier, M.; Chattopadhyay, S.; Chauvin, A.; Cheshkov, C.; Cheynis, B.; Barroso, V. Chibante; Chinellato, D. D.; Cho, S.; Chochula, P.; Chowdhury, T.; Christakoglou, P.; Christensen, C. H.; Christiansen, P.; Chujo, T.; Cicalo, C.; Cifarelli, L.; Cindolo, F.; Cleymans, J.; Colamaria, F.; Colella, D.; Collu, A.; Colocci, M.; Concas, M.; Balbastre, G. Conesa; del Valle, Z. Conesa; Contin, G.; Contreras, J. G.; Cormier, T. M.; Morales, Y. Corrales; Cortese, P.; Cosentino, M. R.; Costa, F.; Costanza, S.; Crkovska, J.; Crochet, P.; Cuautle, E.; Cunqueiro, L.; Dabrowski, D.; Dahms, T.; Dainese, A.; Damas, F. P. A.; Dani, S.; Danisch, M. C.; Danu, A.; Das, D.; Das, I; Das, S.; Dash, A.; Dash, S.; Dashi, A.; De, S.; De Caro, A.; de Cataldo, G.; de Conti, C.; de Cuveland, J.; De Falco, A.; De Gruttola, D.; De Marco, N.; De Pasquale, S.; De Souza, R. D.; Degenhardt, H. F.; Deisting, A.; Deloff, A.; Delsanto, S.; Dhankher, P.; Di Bari, D.; Di Mauro, A.; Diaz, R. A.; Dietel, T.; Dillenseger, P.; Ding, Y.; Divia, R.; Djuvsland, O.; Dobrin, A.; Domenicis Gimenez, D.; Doenigus, B.; Dordic, O.; Dubey, A. K.; Dubla, A.; Dudi, S.; Duggal, A. K.; Dukhishyam, M.; Dupieux, P.; Ehlers, R. J.; Elia, D.; Engel, H.; Epple, E.; Erazmus, B.; Erhardt, F.; Erokhin, A.; Ersdal, M. R.; Espagnon, B.; Eulisse, G.; Eum, J.; Evans, D.; Evdokimov, S.; Fabbietti, L.; Faggin, M.; Faivre, J.; Fantoni, A.; Fasel, M.; Feldkamp, L.; Feliciello, A.; Feofilov, G.; Fernandez Tellez, A.; Ferrero, A.; Ferretti, A.; Festanti, A.; Feuillard, V. J. G.; Figiel, J.; Filchagin, S.; Finogeev, D.; Fionda, F. M.; Fiorenza, G.; Flor, F.; Floris, M.; Foertsch, S.; Foka, P.; Fokin, S.; Fragiacomo, E.; Francisco, A.; Frankenfeld, U.; Fronze, G. G.; Fuchs, U.; Furget, C.; Furs, A.; Girard, M. Fusco; Gaardhoje, J. J.; Gagliardi, M.; Gago, A. M.; Gajdosova, K.; Galvan, C. D.; Ganoti, P.; Garabatos, C.; Garcia-Solis, E.; Garg, K.; Gargiulo, C.; Garner, K.; Gasik, P.; Gauger, E. F.; Gay Ducati, M. B.; Germain, M.; Ghosh, J.; Ghosh, P.; Ghosh, S. K.; Gianotti, P.; Giubellino, P.; Giubilato, P.; Glaessel, P.; Gomez Coral, D. M.; Ramirez, A. Gomez; Gonzalez, V; Gonzalez-Zamora, P.; Gorbunov, S.; Gorlich, L.; Gotovac, S.; Grabski, V; Graczykowski, L. K.; Graham, K. L.; Greiner, L.; Grelli, A.; Grigoras, C.; Grigoriev, V; Grigoryan, A.; Grigoryan, S.; Gronefeld, J. M.; Grosa, F.; Grosse-Oetringhaus, J. F.; Grosso, R.; Guernane, R.; Guerzoni, B.; Guittiere, M.; Gulbrandsen, K.; Gunji, T.; Gupta, A.; Gupta, R.; Guzman, I. B.; Haake, R.; Habib, M. K.; Hadjidakis, C.; Hamagaki, H.; Hamar, G.; Hamid, M.; Hamon, J. C.; Hannigan, R.; Haque, M. R.; Harlenderova, A.; Harris, J. W.; Harton, A.; Hassan, H.; Hatzifotiadou, D.; Hauer, P.; Hayashi, S.; Heckel, S. T.; Hellbaer, E.; Helstrup, H.; Herghelegiu, A.; Hernandez, E. G.; Herrera Corral, G.; Herrmann, F.; Hetland, K. F.; Hilden, T. E.; Hillemanns, H.; Hills, C.; Hippolyte, B.; Hohlweger, B.; Horak, D.; Hornung, S.; Hosokawa, R.; Hota, J.; Hristov, P.; Huang, C.; Hughes, C.; Huhn, P.; Humanic, T. J.; Hushnud, H.; Husova, L. A.; Hussain, N.; Hussain, T.; Hutter, D.; Hwang, D. S.; Iddon, J. P.; Ilkaev, R.; Inaba, M.; Ippolitov, M.; Islam, M. S.; Ivanov, M.; Ivanov, V; Izucheev, V; Jacak, B.; Jacazio, N.; Jacobs, P. M.; Jadhav, M. B.; Jadlovska, S.; Jadlovsky, J.; Jaelani, S.; Jahnke, C.; Jakubowska, M. J.; Janik, M. A.; Jercic, M.; Jevons, O.; Bustamante, R. T. Jimenez; Jin, M.; Jones, P. G.; Jusko, A.; Kalinak, P.; Kalweit, A.; Kang, J. H.; Kaplin, V; Kar, S.; Uysal, A. Karasu; Karavichev, O.; Karavicheva, T.; Karczmarczyk, P.; Karpechev, E.; Kebschull, U.; Keidel, R.; Keil, M.; Ketzer, B.; Khabanova, Z.; Khan, A. M.; Khan, S.; Khan, S. A.; Khanzadeev, A.; Kharlov, Y.; Khatun, A.; Khuntia, A.; Kielbowicz, M. M.; Kileng, B.; Kim, B.; Kim, D.; Kim, D. J.; Kim, E. J.; Kim, H.; Kim, J. S.; Kim, J.; Kim, M.; Kim, S.; Kim, T.; Kindra, K.; Kirsch, S.; Kisel, I; Kiselev, S.; Kisiel, A.; Klay, J. L.; Klein, C.; Klein, J.; Klein, S.; Klein-Boesing, C.; Klewin, S.; Kluge, A.; Knichel, M. L.; Knospe, A. G.; Kobdaj, C.; Kofarago, M.; Koehler, M. K.; Kollegger, T.; Kondratyeva, N.; Kondratyuk, E.; Konopka, P. J.; Konyushikhin, M.; Koska, L.; Kovalenko, O.; Kovalenko, V; Kowalski, M.; Kralik, I; Kravcakova, A.; Kreis, L.; Krivda, M.; Krizek, F.; Krueger, M.; Kryshen, E.; Krzewicki, M.; Kubera, A. M.; Kucera, V; Kuhn, C.; Kuijer, P. G.; Kumar, L.; Kumar, S.; Kundu, S.; Kurashvili, P.; Kurepin, A.; Kurepin, A. B.; Kushpil, S.; Kvapil, J.; Kweon, M. J.; Kwon, Y.; La Pointe, S. L.; La Rocca, P.; Lai, Y. S.; Langoy, R.; Lapidus, K.; Lardeux, A.; Larionov, P.; Laudi, E.; Lavicka, R.; Lazareva, T.; Lea, R.; Leardini, L.; Lee, S.; Lehas, F.; Lehner, S.; Lehrbach, J.; Lemmon, R. C.; Leon Monzon, I; Levai, P.; Li, X.; Li, X. 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C.; Zardoshti, N.; Zarochentsev, A.; Zavada, P.; Zaviyalov, N.; Zbroszczyk, H.; Zhalov, M.; Zhang, X.; Zhang, Y.; Zhang, Z.; Zhao, C.; Zherebchevskii, V; Zhigareva, N.; Zhou, D.; Zhou, Y.; Zhou, Z.; Zhu, H.; Zhu, J.; Zhu, Y.; Zichichi, A.; Zimmermann, M. B.; Zinovjev, G.; Zurlo, N.Acharya, S.; Acosta, F. T.; Adamova, D.; Adhya, S. P.; Adler, A.; Adolfsson, J.; Aggarwal, M. M.; Rinella, G. Aglieri; Agnello, M.; Ahammed, Z.; Ahmad, S.; Ahn, S. U.; Aiola, S.; Akindinov, A.; Al-Turany, M.; Alam, S. N.; Albuquerque, D. S. D.; Aleksandrov, D.; Alessandro, B.; Alfanda, H. M.; Alfaro Molina, R.; Ali, B.; Ali, Y.; Alici, A.; Alkin, A.; Alme, J.; Alt, T.; Altenkamper, L.; Altsybeev, I; Anaam, M. N.; Andrei, C.; Andreou, D.; Andrews, H. A.; Andronic, A.; Angeletti, M.; Anguelov, V; Anson, C.; Anticic, T.; Antinori, F.; Antonioli, P.; Anwar, R.; Apadula, N.; Aphecetche, L.; Appelshaeuser, H.; Arcelli, S.; Arnaldi, R.; Arratia, M.; Arsene, I. C.; Arslandok, M.; Augustinus, A.; Averbeck, R.; Azmi, M. D.; Badala, A.; Baek, Y. W.; Bagnasco, S.; Bailhache, R.; Bala, R.; Baldisseri, A.; Ball, M.; Baral, R. C.; Barbera, R.; Barioglio, L.; Barnafoldi, G. G.; Barnby, L. S.; Barret, V; Bartalini, P.; Barth, K.; Bartsch, E.; Bastid, N.; Basu, S.; Batigne, G.; Batyunya, B.; Batzing, P. C.; Bauri, D.; Bazo Alba, J. L.; Bearden, I. G.; Bedda, C.; Behera, N. K.; Belikov, I; Bellini, F.; Bello Martinez, H.; Bellwied, R.; Beltran, L. G. E.; Belyaev, V; Bencedi, G.; Beole, S.; Bercuci, A.; Berdnikov, Y.; Berenyi, D.; Bertens, R. A.; Berzano, D.; Betev, L.; Bhasin, A.; Bhat, I. R.; Bhatt, H.; Bhattacharjee, B.; Bianchi, A.; Bianchi, L.; Bianchi, N.; Bielcik, J.; Bielcikova, J.; Bilandzic, A.; Biro, G.; Biswas, R.; Biswas, S.; Blair, J. T.; Blau, D.; Blume, C.; Boca, G.; Bock, F.; Bogdanov, A.; Boldizsar, L.; Bolozdynya, A.; Bombara, M.; Bonomi, G.; Bonora, M.; Borel, H.; Borissov, A.; Borri, M.; Botta, E.; Bourjau, C.; Bratrud, L.; Braun-Munzinger, P.; Bregant, M.; Broker, T. A.; Broz, M.; Brucken, E. J.; Bruna, E.; Bruno, G. E.; Buckland, M. D.; Budnikov, D.; Buesching, H.; Bufalino, S.; Buhler, P.; Buncic, P.; Busch, O.; Buthelezi, Z.; Butt, J. B.; Buxton, J. T.; Caffarri, D.; Caines, H.; Caliva, A.; Calvo Villar, E.; Camacho, R. S.; Camerini, P.; Capon, A. A.; Carnesecchi, F.; Castellanos, J. Castillo; Castro, A. J.; Casula, E. A. R.; Sanchez, C. Ceballos; Chakraborty, P.; Chandra, S.; Chang, B.; Chang, W.; Chapeland, S.; Chartier, M.; Chattopadhyay, S.; Chauvin, A.; Cheshkov, C.; Cheynis, B.; Barroso, V. Chibante; Chinellato, D. D.; Cho, S.; Chochula, P.; Chowdhury, T.; Christakoglou, P.; Christensen, C. H.; Christiansen, P.; Chujo, T.; Cicalo, C.; Cifarelli, L.; Cindolo, F.; Cleymans, J.; Colamaria, F.; Colella, D.; Collu, A.; Colocci, M.; Concas, M.; Balbastre, G. Conesa; del Valle, Z. Conesa; Contin, G.; Contreras, J. G.; Cormier, T. M.; Morales, Y. Corrales; Cortese, P.; Cosentino, M. R.; Costa, F.; Costanza, S.; Crkovska, J.; Crochet, P.; Cuautle, E.; Cunqueiro, L.; Dabrowski, D.; Dahms, T.; Dainese, A.; Damas, F. P. A.; Dani, S.; Danisch, M. C.; Danu, A.; Das, D.; Das, I; Das, S.; Dash, A.; Dash, S.; Dashi, A.; De, S.; De Caro, A.; de Cataldo, G.; de Conti, C.; de Cuveland, J.; De Falco, A.; De Gruttola, D.; De Marco, N.; De Pasquale, S.; De Souza, R. D.; Degenhardt, H. F.; Deisting, A.; Deloff, A.; Delsanto, S.; Dhankher, P.; Di Bari, D.; Di Mauro, A.; Diaz, R. A.; Dietel, T.; Dillenseger, P.; Ding, Y.; Divia, R.; Djuvsland, O.; Dobrin, A.; Domenicis Gimenez, D.; Doenigus, B.; Dordic, O.; Dubey, A. K.; Dubla, A.; Dudi, S.; Duggal, A. K.; Dukhishyam, M.; Dupieux, P.; Ehlers, R. 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K.; Kollegger, T.; Kondratyeva, N.; Kondratyuk, E.; Konopka, P. J.; Konyushikhin, M.; Koska, L.; Kovalenko, O.; Kovalenko, V; Kowalski, M.; Kralik, I; Krav
First measurement of Ωc0 production in pp collisions at s=13 TeV
The inclusive production of the charmâstrange baryon 0 c is measured for the first time via its hadronic â decay into âÏ+ at midrapidity (|y| <0.5) in protonâproton (pp) collisions at the centre-of-mass energy s =13 TeV with the ALICE detector at the LHC. The transverse momentum (pT) differential cross section multiplied by the branching ratio is presented in the interval 2 < pT < 12 GeV/c. The pT dependence of the 0 c-baryon production relative to the prompt D0-meson and to the prompt 0 c-baryon production is compared to various models that take different hadronisation mechanisms into consideration. In the measured pT interval, the ratio of the pT-integrated cross sections of 0 c and prompt + c baryons multiplied by the âÏ+ branching ratio is found to be larger by a factor of about 20 with a significance of about 4Ï when compared to e+eâ collisions
Elliptic flow of charged particles at midrapidity relative to the spectator plane in PbâPb and XeâXe collisions
Measurements of the elliptic flow coefficient relative to the collision plane defined by the spectator neutrons v2{ SP} in collisions of Pb ions at center-of-mass energy per nucleonânucleon pair â 2.76 TeV and Xe ions at â sNN = sNN =5.44 TeV are reported. The results are presented for charged particles produced at midrapidity as a function of centrality and transverse momentum for the 5â70% and 0.2â6 GeV/c ranges, respectively. The ratio between v2{ SP} and the elliptic flow coefficient relative to the participant plane v2{4}, estimated using four-particle correlations, deviates by up to 20% from unity depending on centrality. This observation differs strongly from the magnitude of the corresponding eccentricity ratios predicted by the TRENTo and the elliptic power models of initial state fluctuations that are tuned to describe the participant plane anisotropies. The differences can be interpreted as a decorrelation of the neutron spectator plane and the reaction plane because of fragmentation of the remnants from the colliding nuclei, which points to an incompleteness of current models describing the initial state fluctuations. A significant transverse momentum dependence of the ratio v2{ SP}/v2{4} is observed in all but the most central collisions, which may help to understand whether momentum anisotropies at low and intermediate transverse momentum have a common origin in initial state f luctuations. The ratios of v2{ SP} and v2{4} to the corresponding initial state eccentricities for XeâXe and PbâPb collisions at similar initial entropy density show a difference of (7.0 ±0.9)%with an additional variation of +1.8% when including RHIC data in the TRENTo parameter extraction. These observations provide new experimental constraints for viscous effects in the hydrodynamic modeling of the expanding quarkâgluon plasma produced in heavy-ion collisions at the LHC
Carriage of HLA-B*5701 and a haplotypic Hsp70-Hom variant is associated with a Class I MHC-restricted hypersensitivity response to abacavir
Background: Susceptibility to a clinically significant drug hypersensitivity syndrome associated with abacavir use has a significant genetic component. We have shown that the presence of HLA-B*5701 strongly predicts abacavir (ABC) hypersensitivity, particularly in combination with other allelic markers specific to the 57.1 ancestral haplotype, and identified a potential susceptibility locus within a 300-kb region between MEGT1 and C4A6 loci in the central MHC. Here we used fine recombinant haplotype mapping to identity the susceptibility loci.
Methods: We studied 248 consecutive ABC-exposed individuals, representing full ascertainment of ABC use in the Western Australian HIV Cohort study. Hypersensitivity was definite in 18 cases (7.3%); 230 tolerant controls were identified, utilizing an updated clinical classification that included corroborative epicutaneous skin patch test. Patients were typed for genetic markers using standard molecular techniques. Intracellular measurement of TNF (3-color flow cytometry) and intracellular localization of Hsp70 and HLA-B57 (confocal microscopy) were undertaken on abacavir exposed ex vivo polymorphic blood mononuclear cell (PBMC) cultures.
Results: Recombinant mapping in patients with allelic markers of the 57.1 ancestral haplotype suggest a susceptibility locus within the Hsp70 gene cluster. HLA-B*5701 was present in 94.4% of hypersensitive cases and 1.7% of controls (OR 960, p <0.00001). A haplotypic non-synonymous polymorphism of Hsp70-Hom (HspA1L, M493T) was found in combination with HLA-B*5701 in 94.4% of hypersensitive cases and 0.4% of controls (OR 3893, p <0.00001). The Hsp70-Hom M493T allele was present in 22% of controls (OR 60, p <0.00001), suggesting that the combination of HLA-B*5701 and Hsp70-Hom M493T conferred susceptibility. Individuals hypersensitive to ABC exhibited a significantly higher proportion of monocytes expressing TNF in response to ex vivo ABC stimulation, which was abrogated, on depletion of CD8+ T cells from whole blood. Increased intracellular expression of Hsp70 and HLA-B57 molecules in abacavir exposed ex vivo cultured PBMCs was observed in hypersensitive patients compared with controls. Hsp70 and HLA-B57 molecules co-localized within discrete vesicles.
Conclusions: These data indicate that the presence of HLA-B*5701 and Hsp70-Hom M493T are predisposing factors in the development of hypersensitivity to ABC, and implicates them in the generation of a Class I-restricted pathogenic immune response
Detection of KIR2DL4 alleles by sequencing and SSCP reveals a common allele with a shortened cytoplasmic tail
Single-stranded conformation polymorphism (SSCP) by capillary electrophoresis was assessed as a screening and typing method for alleles of KIR2DL4. Exon 6 was investigated as this exon was reported to include three polymorphic nucleotides. Exon 6, intron 6 and exon 7 were amplified as a single polymerase chain reaction (PCR) product of 650 bp from genomic DNA. The PCR product was sequenced and analysed by SSCP. Exon 7 was found to be invariant. Only two nucleotides were found to be polymorphic in exon 6 and another three were found in intron 6. Strong linkage disequilibrium was found between the polymorphic nucleotides resulting in the presence of three alleles in a panel of 20 cell lines. Two alleles differed within intron 6 while the third allele differed at two nucleotides in exon 6. All six possible genotypes were distinguishable by SSCP providing information from both the forward and reverse primers was used. Exon 6 of one allele was one nucleotide shorter than that of the other alleles and the resulting frame shift is predicted to produce a truncated cytoplasmic tail due to a premature stop codon four codons into exon 7. SSCP was found to be an efficient method of typing exons 6 and 7 in a panel of 46 bone marrow donors. All three alleles were found to be common and one was in strong linkage disequilibrium with the presence of another KIR sequence KIR3DS1
Contributions of vitamin D response elements and HLA promoters to multiple sclerosis risk
Objective: The identification of a vitamin D-responsive (VDRE) motif within the HLA-DRB1*15:01 promoter region provides an attractive explanation for the combined effects of HLA-DR inheritance and vitamin D exposure on multiple sclerosis (MS) risk. We therefore sought to incorporate HLA-DRB1 promoter variation, including the VDRE motif, in an assessment of HLA-DRB1-associated MS risk.
Methods: We utilized 32 homozygous HLA cell lines (covering 17 DRB1 alleles) and 53 heterozygote MS samples (20 DRB1 alleles) for HLA-DRB1 promoter sequencing. The influence of HLA-DRB1 variation on MS risk was then assessed among 466 MS cases and 498 controls.
Results: The majority of HLA*DRB1 alleles (including HLA-DRB1*15:01) express the functional VDRE motif, apart from HLA-DRB1*04, *07, and *09 alleles that comprise the HLA-DR53 serologic group. Allele-specific variation within functional X-box and Y-box motifs was also associated with serologically defined HLA-DR haplotypes. Incorporating these results in an analysis of MS risk, we identified a strong protective effect of HLA-DRB1*04, *07, and *09 (DR53) alleles (p = 10(-12)) and elevated risk associated with DRB1*15 and *16 (DR51) and *08 (DR8) alleles (p < 10(-18)).
Conclusions: HLA-DRB1 groups corresponding to serologic HLA-DR profiles as well as promoter polymorphism haplotypes effectively stratified MS risk over an 11-fold range, suggesting functional relationships between risk-modifying HLA-DRB1 alleles. An independent contribution of VDRE motif variation to increase MS risk was not discernible, although vitamin D-dependent regulation of HLA-DR expression may still play an important role given that HLA-DRB1*04/*07/*09 (DR53) alleles that express the "nonresponsive" VDRE motif were associated with significantly reduced risk of MS
Genomic structure, localisation, and polymorphism studies of SAP2a and SAPK4
No abstract availabl
Major histocompatibility complex (MHC) complement deficiency, ancestral haplotypes and systemic lupus erythematosus (SLE): C4 deficiency explains some but not all of the influence of the MHC
In 1982 we reported that among Caucasians with systemic lupus erythematosus (SLE) there is an increased frequency of C4A null. As this allele occurs on the HLA-A1,B8,BfS, C4AQO,B1,DR3 (8.1) supratype, we suggested this accounted for the reported association of B8 and DR3. Since then we have shown that many supratypes including 8.1 identify unique segments of DNA conserved from a common but remote ancestor. Many of these ancestral haplotypes (AH), including 8.1, carry disease genes and some bear C4 null. We have therefore tested the hypothesis that in SLE C4 null alleles are directly involved by examining (1) whether all or only some AH bearing C4 null alleles are increased, (2) whether C4 null is increased in all racial groups examined, and (3) whether C4 null is associated with the presence of antinuclear antibodies (ANA) in the absence of SLE. We performed HLA and complement allotyping on 62 Australian Caucasians and 9 Australian aborigines with SLE and on the 10 out of 133 healthy individuals with 7 or more international units of ANA. Our data confirm an association of C4A null in Australian Caucasians (gene frequency 0.30 versus 0.15 in controls) and show an increased frequency of C4B null in Australian aborigines (gene frequency 0.33 versus 0.22). A review of an extensive literature shows C4A and/or C4B null are increased in all racial groups examined. On the other hand, the HLA-A3,B7,BfS,C4A3,B1,DR2 (7.1) AH rather than C4 null is associated with ANA in health. Our data indicate that while C4 nulls contribute to MHC susceptibility, other genes are likely to be involved
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