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Genome-wide minor histocompatibility matching as related to the risk of graft-versus-host disease.
Martin, Paul J; Levine, David M; Storer, Barry E; Warren, Edus H; Zheng, Xiuwen; Nelson, Sarah C; Smith, Anajane G; Mortensen, Bo K; Hansen, John A.
Afiliación
  • Martin PJ; Division of Clinical Research, Fred Hutchinson Cancer Research Center, Seattle, WA.
  • Levine DM; Department of Medicine, and.
  • Storer BE; Department of Biostatistics, University of Washington, Seattle, WA.
  • Warren EH; Division of Clinical Research, Fred Hutchinson Cancer Research Center, Seattle, WA.
  • Zheng X; Division of Clinical Research, Fred Hutchinson Cancer Research Center, Seattle, WA.
  • Nelson SC; Department of Medicine, and.
  • Smith AG; Department of Biostatistics, University of Washington, Seattle, WA.
  • Mortensen BK; Department of Biostatistics, University of Washington, Seattle, WA.
  • Hansen JA; Division of Clinical Research, Fred Hutchinson Cancer Research Center, Seattle, WA.
Blood ; 129(6): 791-798, 2017 02 09.
Article en En | MEDLINE | ID: mdl-27872059
The risk of acute graft-versus-host disease (GVHD) is higher after allogeneic hematopoietic cell transplantation (HCT) from unrelated donors as compared with related donors. This difference has been explained by increased recipient mismatching for major histocompatibility antigens or minor histocompatibility antigens. In the current study, we used genome-wide arrays to enumerate single nucleotide polymorphisms (SNPs) that produce graft-versus-host (GVH) amino acid coding differences between recipients and donors. We then tested the hypothesis that higher degrees of genome-wide recipient GVH mismatching correlate with higher risks of GVHD after allogeneic HCT. In HLA-genotypically matched sibling recipients, the average recipient mismatching of coding SNPs was 9.35%. Each 1% increase in genome-wide recipient mismatching was associated with an estimated 20% increase in the hazard of grades III-IV GVHD (hazard ratio [HR], 1.20; 95% confidence interval [CI], 1.05-1.37; P = .007) and an estimated 22% increase in the hazard of stage 2-4 acute gut GVHD (HR, 1.22; 95% CI, 1.02-1.45; P = .03). In HLA-A, B, C, DRB1, DQA1, DQB1, DPA1, DPB1-phenotypically matched unrelated recipients, the average recipient mismatching of coding SNPs was 17.3%. The estimated risks of GVHD-related outcomes in HLA-phenotypically matched unrelated recipients were low, relative to the large difference in genome-wide mismatching between the 2 groups. In contrast, the risks of GVHD-related outcomes were higher in HLA-DP GVH-mismatched unrelated recipients than in HLA-matched sibling recipients. Taken together, these results suggest that the increased GVHD risk after unrelated HCT is predominantly an effect of HLA-mismatching.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Antígenos de Histocompatibilidad Menor / Trasplante de Células Madre Hematopoyéticas / Enfermedad Injerto contra Huésped / Antígenos HLA Tipo de estudio: Diagnostic_studies / Etiology_studies / Prognostic_studies / Risk_factors_studies Límite: Adolescent / Adult / Child / Child, preschool / Female / Humans / Infant / Male / Newborn Idioma: En Revista: Blood Año: 2017 Tipo del documento: Article Pais de publicación: Estados Unidos
Texto completo
Añadir a Mi BVS
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XML
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Antígenos de Histocompatibilidad Menor / Trasplante de Células Madre Hematopoyéticas / Enfermedad Injerto contra Huésped / Antígenos HLA Tipo de estudio: Diagnostic_studies / Etiology_studies / Prognostic_studies / Risk_factors_studies Límite: Adolescent / Adult / Child / Child, preschool / Female / Humans / Infant / Male / Newborn Idioma: En Revista: Blood Año: 2017 Tipo del documento: Article Pais de publicación: Estados Unidos