Spectrum of HLA associations: the case of medically refractory pediatric acute lymphoblastic leukemia.

Immunogenetics
William KlitzElizabeth Trachtenberg

Abstract

Although studies of HLA and disease now date back some 50 years, a principled understanding of that relationship has been slow to emerge. Here, we examine the associations of three HLA loci with medically refractory pediatric acute lymphoblastic leukemia (pALL) patients in a case-control study involving 2,438 cases and 41,750 controls. An analysis of alleles from the class I loci, HLA-A and HLA-B, and the class II locus DRB1 illuminates a spectrum of extremely significant allelic associations conferring both predisposition and protection. Genotypes constructed from predisposing, protective, and neutral allelic categories point to an additive mode of disease causation. For all three loci, genotypes homozygous for predisposing alleles are at highest disease risk while the favorable effect of homozygous protective genotypes is less striking. Analysis of A-B and B-DRB1 haplotypes reveals locus-specific differences in disease effects, while that all three loci influence pALL; the influence of HLA-B is greater than that of HLA-A, and the predisposing effect of DRB1 exceeds that of HLA-B. We propose that the continuum in disease susceptibility suggests a system in which many alleles take part in disease predisposition based on differe...Continue Reading

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Citations

Dec 15, 2012·International Journal of Hematology·Kevin Y UrayamaShuki Mizutani
Apr 10, 2015·Reviews in Medical Virology·Jonathan R Kerr, Derek L Mattey
May 11, 2013·Tumour Biology : the Journal of the International Society for Oncodevelopmental Biology and Medicine·Lyubov E SalnikovaAlexander V Rubanovich
Dec 24, 2013·BioMed Research International·Javier Fernández-TorresAlberto López-Reyes

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Methods Mentioned

BETA
genotyping

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