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Titolo:
HLA-DR4-Ala74 ss is associated with risk and poor outcome of severe aplastic anemia
Autore:
Kapustin, SI; Popova, TI; Lyshchov, AA; Imyanitov, EN; Blinov, MN; Abdulkadyrov, KM;
Indirizzi:
Res Inst Hematol & Transfusiol, Dept Biochem, St Petersburg 193024, RussiaRes Inst Hematol & Transfusiol St Petersburg Russia 193024 93024, Russia Res Inst Hematol & Transfusiol, Dept Hematol, St Petersburg, Russia Res Inst Hematol & Transfusiol St Petersburg Russia Petersburg, Russia NN Petrov Oncol Res Inst, Grp Mol Diagnost, St Petersburg, Russia NN Petrov Oncol Res Inst St Petersburg Russia st, St Petersburg, Russia
Titolo Testata:
ANNALS OF HEMATOLOGY
fascicolo: 2, volume: 80, anno: 2001,
pagine: 66 - 71
SICI:
0939-5555(200102)80:2<66:HSIAWR>2.0.ZU;2-K
Fonte:
ISI
Lingua:
ENG
Soggetto:
IMMUNOSUPPRESSIVE THERAPY; PEPTIDE BINDING; HLA; FREQUENCY; RECOGNITION; MECHANISMS; MOLECULES; DISEASE; PROBES; CELLS;
Keywords:
aplastic anemia; gene; HLA-DR antigens; prognosis; susceptibility;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Clinical Medicine
Life Sciences
Citazioni:
25
Recensione:
Indirizzi per estratti:
Indirizzo: Kapustin, SI Res Inst Hematol & Transfusiol, Dept Biochem, 2nd SovietskayaSt,16, St Petersburg 193024, Russia Res Inst Hematol & Transfusiol 2nd Sovietskaya St,16 St Petersburg Russia 193024
Citazione:
S.I. Kapustin et al., "HLA-DR4-Ala74 ss is associated with risk and poor outcome of severe aplastic anemia", ANN HEMATOL, 80(2), 2001, pp. 66-71

Abstract

Severe aplastic anemia (SAA) is a heterogeneous hematological disorder with a high mortality. Genetic predisposition has been shown to play a role ina considerable proportion of SAA cases. For instance, the human lymphocyteantigen HLA-DR2 has been repeatedly demonstrated to be over-represented inSAA patients. In this paper, we expand on the evidence for the contribution of HLA polymorphism in the susceptibility to SAA, which was obtained using the "high-resolution" technique of HLA-DRB1 subtyping. The DRB1*1501 allele appeared to be responsible for the predominance of DR2 specificity in SAA patients and was the most significant risk factor for this disease. It was observed in 23/44 (52.3%) patients versus 22/100 (22.0%) donors [odds ratio (OR) = 3.9; 95% confidence interval (CI): 1.8-8.3; P = 0.0005, correctedP (Pc) < 0.05]. In addition, DRB1*04 alleles also displayed non-random distribution in the SAA group. In particular, DRB1*04 variants coding for alanine at position 74 of the DR<beta>1 chain (HLA-DR4-Ala74 beta subtype) weredetected in all 13 DR4-positive SAA patients but only in 15/24 (62.5%) controls (OR = 16.6; 95% CI: 0.9-312.0; P = 0.015). Multiple comparison analysis confirmed that the HLA-DR4-Ala74 beta subtype confers susceptibility to SAA independently from the DRB1*1501 allele. Finally, examination of the clinical records has shown that the HLA-DR4-Ala74 beta subtype is associated with poor outcome of SAA.

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Documento generato il 03/04/20 alle ore 04:22:14