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Chromosome Y-encoded antigens associate with acute graft-versus-host disease in sex-mismatched stem cell transplant.
Wang, Wei; Huang, Hu; Halagan, Michael; Vierra-Green, Cynthia; Heuer, Michael; Brelsford, Jason E; Haagenson, Michael; Scheuermann, Richard H; Telenti, Amalio; Biggs, William; Pearson, Nathaniel M; Udell, Julia; Spellman, Stephen; Maiers, Martin; Kennedy, Caleb J.
Afiliación
  • Wang W; Center for International Blood and Marrow Transplant Research, Minneapolis, MN.
  • Huang H; Center for International Blood and Marrow Transplant Research, Minneapolis, MN.
  • Halagan M; Program in Bioinformatics and Computational Biology, University of Minnesota, Minneapolis, MN.
  • Vierra-Green C; Center for International Blood and Marrow Transplant Research, Minneapolis, MN.
  • Heuer M; Program in Bioinformatics and Computational Biology, University of Minnesota, Minneapolis, MN.
  • Brelsford JE; Center for International Blood and Marrow Transplant Research, Minneapolis, MN.
  • Haagenson M; Center for International Blood and Marrow Transplant Research, Minneapolis, MN.
  • Scheuermann RH; AmpLab, University of California, Berkeley, Berkeley, CA.
  • Telenti A; Center for International Blood and Marrow Transplant Research, Minneapolis, MN.
  • Biggs W; Center for International Blood and Marrow Transplant Research, Minneapolis, MN.
  • Pearson NM; J. Craig Venter Institute, La Jolla, CA.
  • Udell J; Department of Pathology, University of California, San Diego, San Diego, CA.
  • Spellman S; J. Craig Venter Institute, La Jolla, CA.
  • Maiers M; Human Longevity, Inc., San Diego, CA; and.
  • Kennedy CJ; Root Deep Insight, Inc., Boston, MA.
Blood Adv ; 2(19): 2419-2429, 2018 10 09.
Article en En | MEDLINE | ID: mdl-30262602
Allogeneic hematopoietic stem cell transplantation (allo-HCT) is a curative option for blood cancers, but the coupled effects of graft-versus-tumor and graft-versus-host disease (GVHD) limit its broader application. Outcomes improve with matching at HLAs, but other factors are required to explain residual risk of GVHD. In an effort to identify genetic associations outside the major histocompatibility complex, we conducted a genome-wide clinical outcomes study on 205 acute myeloid leukemia patients and their fully HLA-A-, HLA-B-, HLA-C-, HLA-DRB1-, and HLA-DQB1-matched (10/10) unrelated donors. HLA-DPB1 T-cell epitope permissibility mismatches were observed in less than half (45%) of acute GVHD cases, motivating a broader search for genetic factors affecting clinical outcomes. A novel bioinformatics workflow adapted from neoantigen discovery found no associations between acute GVHD and known, HLA-restricted minor histocompatibility antigens (MiHAs). These results were confirmed with microarray data from an additional 988 samples. On the other hand, Y-chromosome-encoded single-nucleotide polymorphisms in 4 genes (PCDH11Y, USP9Y, UTY, and NLGN4Y) did associate with acute GVHD in male patients with female donors. Males in this category with acute GVHD had more Y-encoded variant peptides per patient with higher predicted HLA-binding affinity than males without GVHD who matched X-paralogous alleles in their female donors. Methods and results described here have an immediate impact for allo-HCT, warranting further development and larger genomic studies where MiHAs are clinically relevant, including cancer immunotherapy, solid organ transplant, and pregnancy.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Trasplante de Células Madre Hematopoyéticas / Predisposición Genética a la Enfermedad / Genes Ligados a Y / Estudios de Asociación Genética / Enfermedad Injerto contra Huésped / Antígenos Tipo de estudio: Prognostic_studies / Risk_factors_studies Límite: Female / Humans / Male Idioma: En Revista: Blood Adv Año: 2018 Tipo del documento: Article Pais de publicación: Estados Unidos
Texto completo
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Trasplante de Células Madre Hematopoyéticas / Predisposición Genética a la Enfermedad / Genes Ligados a Y / Estudios de Asociación Genética / Enfermedad Injerto contra Huésped / Antígenos Tipo de estudio: Prognostic_studies / Risk_factors_studies Límite: Female / Humans / Male Idioma: En Revista: Blood Adv Año: 2018 Tipo del documento: Article Pais de publicación: Estados Unidos